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The effects of novel hybrid exercise rehabilitation on cardiovascular function and orthostatic tolerance.. Wong, Shirley Candice 2008-03-04

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THE EFFECTSOF NOVEL HYBRIDEXERCISEREHABILITATIONON CARDIOVASCULARFUNCTION ANDORTHOSTATICTOLERANCEIN INDIVIDUALSWITH SPINALCORD INJURYbySHIRLEY CANDICEWONGB.Sc., McMasterUniversity, 2006A THESIS SUBMITTEDIN PARTIAL FULFILMENTOF THE REQUIREMENTSFORTHE DEGREE OFMASTER OF SCIENCEinThe Facultyof GraduateStudies(Human Kinetics)THE UNIVERSITYOF BRITISHCOLUMBIA(Vancouver)August2008© Shirley CandiceWong, 2008ABSTRACTPersons with spinalcord injury(SCI) often sufferfrom orthostatichypotension(markedreduction inblood pressureupon assumingan uprightposture) andexercise mayassist with itstreatment byimproving cardiovascularhealth and autonomicregulation.Hybrid exercise(concurrentmovement ofthe arms and legs)promotes enhancementsin venous return,ventricular filling,andcardiorespiratoryfunction. However,limited researchhas evaluatedthe effects of hybridexercise onorthostatic tolerance.Accordingly,this study evaluatedthe effects ofarm and hybridexercise onorthostatic responseand on cardiorespiratoryfunction duringpeak exercise.Additionally,the effectsofspinal cord lesionlevel were examined.Asymptomaticpersons withSCI (C4-T6)and age- andgender-matched able-bodiedcontrols participatedin four testingdays. The firsttwo testing daysexaminedparticipants’orthostatic tolerancefollowing restfollowed bya peak arm cycleor hybrid exercisetest (inrandom order).The final two testingdays assessedthe acute effectsof steady statearm and hybridexercise onorthostatic response(in randomorder). Therewas no significantdecrease(p=O.07) inmiddle cerebralartery bloodvelocity uponassuming theupright positionfollowinga bout of hybridsteady stateexercise inparticipantswith SCI (67.2±18.8 to 61.8±14.8 cms’, respectively).Hybridexercise resultedin significantly (p<O.05)greater cardiorespiratoryrequirementsthroughoutincrementalexercise incomparisonto arm ergometryin all groups.The averagepeak oxygenuptake(across all groups)was 21 ± 9 vs.19 ± 7 mLkgmin-1,for hybridexercise vs.arm ergometry,respectively.The averagepeak oxygenuptake (acrossall modes ofexercise)was 24.9±7.9 vs. 15.7±4.2 mLkgmin-1,for able-bodiedparticipants vs.participantswith SCI, respectively.Furthermore,persons withparaplegiahad significantly(p<O.05) higheroxygen uptakethan personswith tetraplegiaand the averagepeak oxygen uptake(across all modesof exercise)was 18.5±3.7 vs. 12.9±2.4mLkg•min-1for these groups,respectively.Hybrid exerciseimprovedcardiovascularresponse toanorthostaticchallenge andpromoted greatercardiorespiratoryresponse incomparisonto arm exercisein persons withSd. Furthermore,lesion levelof SCI affectsresponsesto an orthostaticchallengeandpeak exercise.TABLE OF CONTENTSABSTRACTiiTABLE OF CONTENTSiiiLIST OF TABLESvLIST OF FIGURESviACKNOWLEDGEMENTSviiDEDICATIONviii1 INTRODUCTION11.1 OrthostaticHypotension21.1.1 Background21.1.2 Underlying Mechanismsof OrthostaticHypotension31.1.3 OrthostaticHypotensionand Exercise51.2 CariodrespiratoryResponse toExercise51.2.1 Upper ExtremityExercise51.2.2 Lower ExtremityExercise61.2.3 Hybrid Exercise61.3 Lesion Levelof Spinal CordInjury71.3.2 Lesion Leveland OrthostaticHypotension81.3.2 Lesion Leveland Exercise82 OBJECTIVES103 HYPOTHESES123.1. OrthostaticHypotension123.2 CardiorespiratoryResponseto IncrementalExercise123.3 Lesion Level124 RESEARCH METHODS134.1 Participants134.1.1 Recruitment144.2 GeneralProtocol144.3 OrthostaticTesting144.3.1 Sit UpTest154.4 TestingDays One andTwo (Randomized)164.4.1 Peak AerobicFitness TestingProtocol(VO2peak Test)164.4.2 PeakAerobic(VO2peak) Arm CycleExercise Testing174.4.3 PeakAerobic(VO2peak) HybridExericse Testing174.5 TestingDays Threeand Four (Randomized)184.6 CardiovascularMeasures184.6.1 MiddleCerebralArtery BloodVelocity184.6.2 ArterialCompliance194.6.3 Blood Pressure194.6.4 Electromyogram194.6.5 FatigueScale194.6.6 HeartRate204.6.7 HeartRate Variability204.6.8 MetabolicCart and ImpedanceCardiography204.6.9 OxyhaemoglobinSaturation204.6.10 TotalPeripheralResistance20III4.6.11 Ratingof PerceivedExertion215 STATISTICALANALYSIS226 RESULTS236.1 OrthostaticHypotension236.1.2 Middle CerebralArtery BloodVelocity236.1.2 Blood Pressure326.1.3 Heart Rate346.1.4 Stroke volume356.1.5 CardiacOutput366.1.6 Total PeripheralResistance376.2 Peak ExerciseTesting386.2.1 Power Output386.2.2 Peak OxygenUptake(VO2peak)406.2.3 Peak HeartRate, StrokeVolume, CardiacOutput, and Arterio-venousOxygenDifference436.2.4 Rating of PerceivedExertion496.2.5 Fatigue Scale516.2.6 Arterial Compliance527 DISCUSSION548 LIMITATIONSAND FUTURECONSIDERATIONS679 REFERENCES69ivLIST OF TABLESTable 1. Participantcharacteristics13Table 2. Cardiorespiratoryresponses to peak exercisetesting41VLIST OF FIGURESFigure 1. Middle cerebralartery bloodvelocity duringthe orthostatic challengein participants withSCI24Figure 2. Middle cerebralartery blood velocityduring the orthostaticchallenge in participantswithtetraplegia25Figure 3. Middlecerebral artery bloodvelocity duringthe orthostatic challengein participants withtetraplegia26Figure 4. Middle cerebralartery blood velocityduring the orthostaticchallenge in able-bodiedindividuals27Figure 5. Middle cerebralartery blood velocityduring the orthostaticchallenge followingrest inparticipants28Figure 6. The flow-pressurerelationship betweenthe initial supine positionand assumption oftheupright postureduring the orthostaticchallenge29Figure 7. Temporalchanges in meanarterial pressureduring the orthostaticchallenge31Figure 8. Temporalchanges in middlecerebral arteryblood velocityduring the orthostaticchallenge32Figure 9. Temporalchanges in systolicblood pressureduring the orthostaticchallenge33Figure 10. Temporalchanges in diastolicblood pressureduring the orthostaticchallenge34Figure 11. Temporalchanges in heartrate during theorthostatic challenge35Figure 12. Temporalchanges in strokevolume duringthe orthostaticchallenge36Figure 13. Temporalchanges in cardiacoutput during theorthostaticchallenge37Figure 14. Temporalchanges in totalperipheral resistanceduring theorthostatic challenge38Figure 15. Peakpower output acrossgroups during incrementalarm and hybridexercise39Figure 16. Peakpower output duringincremental hybridexercise40Figure 17. Oxygenuptake for able-bodiedparticipants,and participantswith paraplegiaandtetraplegia duringincremental armand hybrid exercisetests to exhaustion42Figure 18. Heartrate in able-bodiedparticipants,and participants withparaplegiaand tetraplegiaduring incrementalarm and hybridexercise teststo exhaustion44Figure 19. Strokevolume in able-bodiedparticipants, andparaplegicsand tetraplegicsduringincremental armand hybrid exerciseto exhaustion45Figure 20. Cardiacoutput in able-bodiedparticipants, andparaplegicsand tetraplegicsduringincremental armand hybrid exerciseto exhaustion46Figure 21. Peakcardiac outputacross groups47Figure 22. Arterio-venousoxygen differencein able-bodiedparticipants,and paraplegicsandtetraplegicsduring incrementalarm and hybridexercise to exhaustion48Figure 23. Ratingof perceived exertionduring incrementalexercise to exhaustionfor able-bodiedparticipants, andparaplegicsand tetraplegics50Figure 24. Responseto questions inthe fatigue scale(across groups)52Figure 25.Arterial compliancein participantswith SCI and able-bodiedparticipants53viACKNOWLEDGEMENTSI would like to extenda very special thankyou to my supervisor,Dr. Darren Warburton,whoseguidance, and unrelentingsupport and patiencehave been invaluableto me. Dr. Warburton’sresearchexpertise and knowledge,thoroughness,genuine enthusiasm,and unwavering faithin me will alwaysbe appreciated. I wish tothank Andrei Krassioukov,a member of my supervisorycommittee and theattending physicianfor my study, for hisguidance, attentionto detail, motivatingdisplay of hard workand perseverance,and encouragementduring the completionof my degree. I amgrateful for Andrei’seagerness to instructand challenge me.I also wish to thankShannon Bredin,a member of mysupervisory committee,for her guidance andinstruction duringthe pursuit of my degree.I am very appreciativeof the help from JessicaScott, Ben Esch,and Jordan Queridowhospent numeroushours teaching mehow to use equipmentand to analyzedata, and who providedagreat deal of encouragement.I am also thankfulfor the help, support,and friendshipof members ofthe CardiovascularPhysiology andRehabilitation and Cognitiveand Functional LearningIaboratoes.viiDEDICATIONI would like to dedicatethis thesis tomy Mum, Ann Wong,and my Dad, PeterWong, who havealways allowed meto select my own path,and never expressedthat I cannot pursueor accomplisheverything I want.With their unconditionallove, support, andencouragement, Iam inspired everydayto be more than Iam today for tomorrow.vi”I INTRODUCTIONOne of the many physiologicalchanges that Individualswith spinal cordinjury (SCI) experienceincludes dramaticchanges to the functioningof their autonomic nervoussystem. Subsequently,impaired sympathetic activityand completemuscle paralysis belowthe level of the spinalcord lesionproduces an absence ofsympathetic-mediatedvasoconstriction andvoluntary musclepump action1,which contributesto orthostatic intolerancein this population. Orthostatichypotension isa commonclinical problem for individualswith cervicalor high thoracic levelinjuries2.It is a conditionthat isgenerally characterizedby a reduction in bloodpressure of 20 mmHgor more, or anattenuation indiastolic blood pressureof 10 mmHg or more,upon a change in bodyposition from a supineposition toan upright posture, in thepresence or absenceof symptoms3-5.Thepotential for participationinexercise to help manageorthostatic hypotensionin the personswith SCI is importantsince orthostaticintolerance has beenfound to limit activeand effective participationin rehabilitation programs3.6anddelay the achievementof associated goals7.These have the potentialto hasten the deterioratingeffects of immobilizationand the developmentof undesirablesecondary medicalcomplications7.8Lowblood pressure isalso associated withother conditions whichmay negativelyimpact health, suchasautonomic dysreflexia9.AdditionaNy,learning more aboutmethods to ameliorateorthostatichypotension has thepotential to help improveparticipation in rehabilitationas orthostatic hypotensionisa common obstacle delayingadaptation tosifting during the initialphase of rehabilitationfollowingSC110.Increasing understandingabout orthostaticresponse followinga bout of exercisein thispopulation mayalso be beneficialin determiningthe cardiovascular responseto assuming an uprightposture in a wheelchairfollowing participationin exercise. Accordingly,exercise rehabilitationhasbeen shown to havethe ability to helptreat orthostatic hypotensionas it improves cardiovascularhealth and autonomicregulation11,and stabilizescentral blood volume12.Cardiovasculardisease is the leadingcause of death notonly in able-bodiedindividuals13,butin persons with SCIas well1415Morbidity fromcardiovascular causesin the populationwith SCI isrelatively higherthan that seen in theable-bodied population,and the onset of cardiovasculardiseasetends to occur earlierin persons with SCI16-18.Cardiovascular disordersin both the acute andchronicstages of SCI areamong the mostcommon causes of deathin this population1719,20Evidencedemonstrates thatphysical inactivityis a major independentrisk factor forcardiovasculardisease andpremature mortality21-26.Previous studies havedemonstrated thatparticipation inphysical activityinpersons with SC)helps to improvefitness levels andexercise capacity27-30.Furthermore, exercisetraining involvingthe legs has beenfound to promoteimprovementsin lower-limb circulationandvasoclilatory capacity3132,body composition3334and insulin resistance35,all of which areimportant asparalysis and inactivitypredispose individualswith SCI todecreased lowerlimb circulation36-39,andincreased body fatcompositionand insulin resistance37-39.Accordingly, itmay be postulatedthatexercise that combinesconcurrent activityof the armsand legs may helpto promote greaterbenefits tohealth than eitherarm or leg exercisealone. With theexpected increasein longevity inthe SCIpopulation, currentresearch is focusingon the managementof health issuesassociated withlong-termsurvival40.While resultsfrom several studiessuggest thatexercise can helpto improve cardiovascularhealth, and, thus,potentially orthostaticintolerance, andthat passively exercisingthe lowerlimbs canhelp promote greatercardiorespiratoryresponse in personswithSCl41-,it remains unclearwhat theeffects of an acutebout of steadystate exercise areon orthostatichypotension,and whether passiveinclusion ofthe legs with concurrentarm exercise promotesgreater cardiorespiratoryresponse toexercise in comparisonto arm exercise alone.Thus, these warrantfurther investigation.1.1 OrthostaticHypotension1.1.1 BackgroundOrthostatic hypotension,as previouslydefined, is characterizedby a reductionin bloodpressure upona change in posture.It may be asymptomaticor symptomaticand symptomsincludedizziness, visualimpairment, feelingfaint or presyncope,nausea, fatigue,ringing in theears, cognitiveimpairment, palpitations,headache, neckache, and blackingout5 Inable-bodied individuals,heartrate and bloodpressure controlare coordinatedby the two componentsof the autonomicnervoussystem: the sympatheticand parasympatheticnervous systems9.The parasympatheticnervoussystem is dominantduring rest andreflexly decreasesheart rate whenactivated.In contrast, thesympathetic nervoussystem hasa counteractingand, thus, moreexcitatoryrole. Peripheralresistanceis also increased,and the combinationof these responsesto sympatheticactivation ultimatelyproduces an increasein blood pressure.However, SCI resultsin alterationsto autonomic nervoussystem activity,affecting spinalpathways thatmodulate cardiovascularcontrol9.Spinalcord injuryischaracterizedby a disruptionof the normalautonomic cardiovascularcontrol mechanisms146,leading2to various physiological changes in cardiovascularhealth and functioning. In relationto blood pressurecontrol, sympathetic hypoactivityand unopposed vagal parasympatheticcontrol often result followinginjury47,ultimately leadingto low resting blood pressure4849Following injury, autonomic nervoussystem impairments result in a varietyof cardiovascular abnormalities,including alterations in bloodpressure control9,as previously mentioned.Specifically, low levels of efferentsympathetic nervousactivity and the loss of reflex vasoconstrictionfollowing SCI have been associatedwith orthostatichypotension3.1.1.2 Underlying Mechanismsof Orthostatic HypotensionThere are several mechanismsthat are postulated to lead to orthostatichypotension. Impairedsympathetic control and cerebral autoregulationwere the main focuses ofthis investigation.Impaired sympathetic control is commonfollowing injury when SCI occursabove the majorsympathetic splanchnic outflow(T6). This causes sympathetic impulsesto the splanchnic vascularbeds and lower limbs o be restricted50.This limits vasoconstriction andsubsequently affects bloodpressure regulation, leading to aninability to counteract a drop inarterial blood pressure51.Injuryabove T6 alters the efferent dischargesfrom the brain stem to the sympatheticnerves that causevasoconstriction in the splanchnic circulationand lower limbs. This has a largenegative impact on thebody’s ability to properly regulateshort-term pressure control52.Furthermore, impaired sympatheticactivity, or a low level of efferentsympathetic nervous activity, andcomplete muscle paralysis belowthe lesion level limits sympathetic-mediatedvasoconstriction and voluntary musclepumping action53,respectively, and these are associatedwith orthostatic hypotension3.Subsequently,following injury,persons with SCI experience sympathetichypoactivity as a resultof disruption of the descendingspinalcardiovascular pathways9.Individuals with SCI generally haveaverage basal systolicand diastolicblood pressures about l5mmHglower than their able-bodied counterparts1.Another mechanismthat has been postulated relatesto cerebral autoregulation.In the ablebodied population, cerebral bloodflow is governed by autoregulationand changes in pressurearecounteracted by changesin cerebrovascular resistancein order to maintain relativelyconstant flow54.When in the supine position,blood is evenly distributedthroughout the body andmean arterialpressure measured at thelevel of the heart matches themean cerebral perfusionpressure (853mmHg)54.Whenin an upright posture,cerebral arterialpressure decreases(15 to 30 mmHg)incomparison topressure at the levelof the heart (aorticarch) as a resultof the vertical height,orhydrostatic, differencebetween the headand the heart54.Furthermore,it has been foundthat theremay be a disruptionof cerebral bloodflow when standingupright, and if thereis a subsequentdecrease in cerebralperfusion, this maylead to symptomsof orthostatic hypotension55.Cerebral hypoperlusionis commonly elicitedby an orthostatic challenge,revealing symptomsof orthostatic hypotensionsuch as dizzinessor fainting (syncope)9.Individuals whoare able tomaintain consciousnesswhen experiencinglow arterialpressures likelyhave a shift in cerebralautoregulationwhich allows themto maintain cerebralblood flow despitelow perfusion pressures56-58,since the underlyingcause symptomsof hypotensionare due to cerebralhypoperfusion9.Approximately60% of individuals whoexperience orthostatichypotension havealtered cerebralhaemodynamicsand exhibit symptoms7.There is evidenceto suggest that cerebralautoregulationis altered inthe persons withSCI. Inindividuals withtetraplegia, thosewith a greater declinein cerebral bloodflow experiencesymptoms oforthostatic hypotension59.Subsequently,it has been suggestedthat adaptationto orthostatichypotension predominantlyinvolves cerebralblood flow, ratherthan systemicblood pressureinpersons with SCI9.Furthermore, theimportance of cerebralblood flow in helpingto control orthostatichypotension ultimatelyinvolves cerebraloxygenation55.This is importantto consider whenin theupright posturebecause if systemicblood pressuredecreasesto low levels, cerebralperfusionpressure declineseven further dueto the vertical heightdifference54,Individuals withSCI have beenfound to experiencesimilar declinesin cerebral oxygenationas their able-bodiedcounterparts,despitegreater falls insystemic bloodpressure60.Thus,whether or notthere is an experienceof orthostatichypotension maybe dependenton the amountof decline in cerebralblood flow, whichin turn mayaffect cerebraloxygenation, butthis is still unclear9.It has beenpostulated that theextent to whichcerebral bloodflow is alteredfollowing injury,and thus, affectsorthostatictolerance, maybe related tolesion levelor completenessof the injury9.41.1.3 OrthostaticHypotension andExerciseThe ability to contractthe muscles ofthe lower limbs hasbeen found to havethe potential toameliorate orthostatichypotension. Orthostaticchallenges producetranslocations inblood volumeaway from the thoracicregion into the lowerextremities61,leadingto blood pooling.As a result,ventricular fillingpressures are attenuatedand stroke volume isreduced61.In able-bodiedindividuals,the redistribution of bloodvolume from thelower limbs and splanchnicregion is mediatedby thecombined actionof various neurohumoraland motor reflexes, helpingto meet the demandof theexercising upper extremitymuscles62.Conversely,vasomotor dysfunctionbelow the level ofthe spinalcord lesion limitsthe ability to redistributeblood from the lowerextremities andsplanchnic region63.However, there isa paucity of informationexamining the effectsof exercise, withoutany electricalstimulation, on orthostatichypotension in personswith SCI, and themajority of the existingliteratureconsiders personswith paraplegia.1.2 CariodrespiratoryResponse to ExerciseAerobic fitnessis a strong predictorof the capacity for activitiesof daily living, and exercisetraining commonlyleads to enhancementsin aerobic fitnessin the general population6465Furthermore, aerobicfitness, as well as othercomponents of health-relatedfitness are positivelyassociated withfunctional improvementsin individuals with SC166,67Accordingly,exercise is a meansby which this populationcan enhance aerobicfitness and promotethe associated benefits.1.2.1 Upper ExtremityExerciseParticipation inexercise has beenshown to help improvefunctional capacityin persons withSCI. Due to thelower limb paralysisfollowing SCI, individualsgenerally performupper body exercisein the form of arm cycling68.During upper bodyexercise, it is generallyobserved inthe able-bodiedpopulationthat their abilityto activate the skeletalmuscle pump enhancesaerobic capacityand overallexercise performance69.The skeletal musclepump helps maintainvenous return, whichproducessufficient cardiacoutput, and thus,oxygen uptake.However, evenfor able-bodied individuals,upperextremity activityis very physicallydemandingand elicits unique cardiovascularresponses incomparison withleg exerciseat equivalent poweroutputs70,such asdecreases in ventricularfilling andstroke volume71,and increasesin total peripheralresistance70,heartrate, and bloodpressure7273•Persons with SCIalso experienceproblems thatarise from circulatoryhypokinesis,a cardiac output5that is lower than expectedfor a given oxygenuptake, which issubsequent toinsufficient venousreturnas a result of inactivityof the skeletal musclepump174-76,leading to bloodpooling in the paralyzedlower limbs70.Whole-bodyexercise hasbeen shown to enhancecardiorespiratoryresponse toagreater extent then armexercise alone inindividuals withSCl7-.Furthermore, voluntaryarm exercise elicitsonly small increasesin maximal oxygenuptake andis thought to be insufficientto promote maintenanceof a high levelof fitness in personswith SCI8°.Upper extremityexercise capacityis limited since venousreturn and,subsequenfly, cardiacoutput, arecompromised, leadingto insufficient blood flowto the active musclesduring exercise70.1.2.2 Lower ExtremityExerciseExercise involvingthe lower extremitiesincorporates theability to utilizethe skeletal musclepump whichhelps to ensure adequatevenous return ofblood during activity.However, in individualswith SCI, the abilityto contract the musclesof the legs independentlyis often lost asa result of lowerlimb paralysisfollowing injury,and this, in turn,limits the cardiorespiratoryresponse to exercise.Fortunately,in persons withSCI, active contractionof the lower limbsvia the applicationof electricalstimulation hasthe potential to activatethe skeletalmuscle pump. Musclecontractionsare inducedthrough microprocessor-controlledelectrical stimulationthat is deliveredvia skin surfaceelectrodesplaced over motorpoints of the quadriceps,hamstring, and glutealmuscle groups8182The skeletalmuscle pumphas an important functionduring exercise.In able-bodiedindividuals, anincrease invenous return iselicited by contractionsof the leg muscles,which provide pressureagainst the veinsand help the venousvalves return bloodto the heart andcentral circulation83. As demonstratedinthe literature, legmuscle contractionssignificantly augmentcardiovasculardynamics in able-bodiedparticipants in comparisonto participants with SCI69,851.2.3 HybridExerciseSince the abilityto utilize the legmuscle pump duringexercise hasbeen shownto helpimprove performance86,it is logical thatrecent researchexamines cardiorespiratorymeasures duringactivity involvingsimultaneous activityof the upper and lowerlimbs. As previouslydiscussed, hybridexercise involvesconcurrent exerciseof the arms and legsand facilitatesactivation of a largermusclemass in comparisonto upper or lowerbody exercise alone.A few studiescomparing hybridexercise to6arm cycle exerciseillustrate that thereis greater cardiorespiratoryresponse tohybrid exerciseinindividuals withSCI77-79.Furthermore,increases in maximaloxygen uptakehave been foundwhenarm exercise hasbeen added to lowerextremity activity elicitedby electrical stimulation87.Hybrid.exercise elicits increasesin oxygen uptake88,and stroke volume7878•The enhancementin strokevolume may implythat exercise involvingthe legs promotes reductionsin venous pooling,andsubsequently, augmentationsin venous return787989While thereare several studiesexaminingcardiorespiratoryresponse to hybridexercise in individualswith SCI, thereis a paucity of informationabout the effectsof passively incorporatingthe legs during hybridexercise in thispopulation,warranting further investigation.1.3 Lesion Levelof Spinal CordInjuryThe common waysin which SCI areclassified areby level, and completeness,or severity ofinjury. Thereare two levels of injury,tetraplegia andparaplegia. Theneurological levelof injury refersto the most caudallevel whereby bothsensory and motorlevels remain intact90.The AmericanSpinalInjury Association(ASIA) has internationalstandards for theneurological classificationof SCIconsisting of: 1)a five category ASIAimpairment scale(A-E), 2) motorscore, and3) sensory score91.Tetraplegia is characterizedby impairment orloss of motorand/or sensoryfunction in the cervicalsegments (C1-C8)of the spinal cord92or the highestthoracic segment(TI)93.Tetraplegiais alsocharacterizedby impairment or lossof motor andlorsensory functionin the upper andlowerextremities, trunkand pelvic organs93.Paraplegia is thesubsequent resultof damage to thoracic(TiT12), lumbar,or sacral segmentsof the cauda equina(L1-L5, S1-S4)of the spinal cord93.Injury to thethoracic segmentsimpairs the trunk,legs, and/or pelvicorgans, while damageto the lumbar orsacralsegments leadsto impairmentsof the legs and/orpelvic organs93.Accordingly, paraplegialeavesmotor andsensory functionintact and normalin the upper extremities.Completenessof injury isbased on the ASIAstandards9294.In terms of completenessorseverity of Sd,an incompleteinjury is characterizedby the partialpreservation ofsome sensoryand/or motorfunction belowthe level of the lesion,and this includessensory and/ormotor functioninthe lowest sacralsegments of the spinalcord (S4 and S5)90.In contrast, subsequentto completeinjuries, there isa loss of motorand sensory functionsthat are conductedvia afferentand efferentspinal pathwaysas well as disruptionof the pathwaysfrom the brainto the peripheralsympathetic7nervous system96,and an absenceof sensory and motorfunction in the lowestsacral segments ofthespinal cord°°. Thisultimately leadsto cardiovascularand metabolic changesat rest and duñngexercise97-101.TheASIA impairment scale91further specifies theseverity of aninjury beyond itsclassification as completeor incomplete. Thus,SC) can be classifiedas follows: completetetraplegia,incomplete tetraplegia,complete paraplegia,and incomplete paraplegia,as well as correspondingASIA level.t3.2 Lesion Leveland Orthostatic HypotensionOrthostatic hypotensionis more commonlyexperienced in individualswith tetraplegia748102Upon a change in posture,tetrplegics experiencegreater decreasesin blood pressure thanparaplegics7.The synergisticrelationship betweenparasympathetic andsympathetic controlis lostfollowing injury, andthis is more pronouncedin individuals withcervical and high thoracicinjuries9.Higher levels ofinjury lead to greaterimpairments of theefferent sympatheticnerves48 and it is highlyprobable that this affectsvascular responsesto orthostasis4749.Furthermore, lesionsabove T6 disruptsupraspinal controlto the splachnic bedand thus, to majorcapacitance vessels,promoting orthostaticinstability9.Normally,while in an uprightposture, thereis a baroreceptor-mediatedvasoconstrictionthat occurs in responseto an increase in tonicsympathetic outflow,and this worksto maintain bloodpressure andcerebral perfusion9.These vascular resistanceresponses arelargely involved incardiovascularcontrol during orthostaticstress103-105.Subsequently,any disruptionto these responsesfollowing injurypromotes orthostaticintolerance’ Lesion Leveland ExerciseLesion level alsoaffects exercise performancein persons with SC).Depending onthe level ofinjury, venous dilation,venous insufficiency,and venous bloodpooling can resultin paralyzed lowerlimbs, affecting exercisecapacity96.Researchhas shown that maximalpower output, maximaloxygenuptake, and totalwork is higher in athleteswith lower lesion levels106.Furthermore, duringexercise, ithas been found thathigher lesion levelsproduce blunted cardiorespiratoryresponses to exerciseincomparison to personswith lower levelinjuries. Whetherat rest or duringsubmaximal or maximallevels of exercise, individualswith tetraplegiahave been found tohave lower valuesfor oxygen uptake,heart rate, work rate,and ventilation in comparisonto paraplegics96.107108On a continuumof injury8levels fromtetraplegic toparaplegic, moderatelevel paraplegiaresults in higherresting andmaximalheart rate andmaximal oxygenuptake incomparison toindividuals with higherlesion levels.92 OBJECTIVESThe primary objectiveof this investigation wasto examine the effects ofacute steady stateexercise on orthostatichypotension. Uponreview of the literature,previous studies haveevaluated theeffects of functional electricalstimulation, or functionalneuromuscular stimulation,on orthostatichypotension following injury.Overall, the methodologycommonly used inthese studies involvedevaluating cardiovascularresponses with and withoutstimulation during graded-tilttests531O9Generally, it has been foundthat in participants withSd, both systolic anddiastolic blood pressureresponses are higher duringtilt tests when stimulationis applied in comparisonto when it is nt.Accordingly, it has beenproposed that stimulationmay be an important treatmentcomponent ofrehabilitation programs, allowingthese individualsto more easily withstandpostural changes involvedin standardizedmobilization (e.g., sittingor standing). In a novelapproach, this studywas designedassess the effects of hybridexercise incorporatingpassive lower extremityexercise on orthostatichypotension instead of employingelectrical stimulation duringorthostatic stress.The secondary objectiveof this study wasto examine and comparethe similarities anddifferences in cardiorespiratoryresponse during peak armcycle exerciseand peak hybrid exerciseinindividuals withSCI and their able-bodiedcounterparts. Upon reviewof the literature, manyexistingstudies that have investigatedthe use of hybrid exerciseutilize functional electricalstimulation to elicitmuscle contractionin the lower limbs. This warrantedinvestigation intothe effectiveness of passivelegcycling in conjunction with armcycling to determine ifactive muscle contractionis required to promoteenhancements in cardiorespiratoryresponse during whole-bodyexercise in personswith SCI.Accordingly, thisstudy was designed to evaluatehybrid exercise thatincorporates passivecycling ofthe lower limbs in individualswith SCI.The final objectiveof this study was to examinethe effects of lesionlevel on orthostaticresponse and cardiorespiratoryresponse to exercise inindividuals with SCI.It was anticipated thatthese findings wouldbe useful for future studies involvingthe population with SCIthat investigate thedevelopment of optimalexercise prescriptionswith the appropriatemode of physical activity,or for theimprovement of exerciserehabilitation programs.In this way, appropriateexercise prescriptionsandrehabilitation programsmay be developed forpersons with SCIbased on their physiologicaldifferencesaccording to injury level.Additionally, the effectsof acute steadystate exercise onorthostatichypotension can betaken into considerationwhen working toimprove exerciserehabilitation practices10for individuals with SCI.This approach wasmeñted as a reviewof the literature revealedthat lesionlevel has a significantimpact on exercise capacityand responseto orthostatic challenge.‘Ii3 HYPOTHESES3.1. OrthostaticHypotensionit was anticipatedthat physiologicalresponsesassociatedwith orthostatichypotension wouldbe improvedfollowinga bout of steadystate exercisein individualswith SCI andable-bodiedindividuals.It was alsopostulated thatpersons with SCIwould experienceblunted bloodpressureresponses incomparisonto their able-bodiedcounterparts.Hybrid exercisewas also expectedtoimprove orthostatictolerance toa greater extentthan arm cyclingexercise.3.2 CardiorespiratoryResponseto IncrementalExerciseWe hypothesizedthat individualswith SCI wouldexhibit lowercardiorespiratoryresponse (i.e.,heart rate, strokevolume, cardiacoutput, oxygenuptake, etc.)to exercise incomparisonto able-bodiedindividuals.We alsohypothesizedthat, for bothgroups of participants,hybrid exercisewould elicitgreater cardiorespiratoryresponsethan arm cyclingexercise, illustratingthe greaterpotential toimprove aerobicfitness withwhole-bodyexercise3.3 LesionLevelWe hypothesizedthat lesionlevel wouldhave an impacton variouscardiovascularresponsesto the orthostaticchallengeand on cardiorespiratoryresponsesto peak exercise.It was anticipatedthat individualswith tetraplegiawould haveblunted cardiorespiratoryresponseto exercise anddemonstratea decreasedability to regulateblood pressurein comparisonto individualswith paraplegiaand able-bodiedindividuals.124 RESEARCH METHODS4.1 ParticipantsSix persons with SCI(C4-T6 lesions)and six age- and gender-matchedcontrols were recruitedfor this investigation (Table1). Participants were27 to 39 years of age,asymptomatic, non-smokers,and were not using medicationsthat would affect theirautonomic, cardiovascular,respiratory, ormetabolic responsivenessto exercise or the orthostaticchallenge employedduring this study. Inorderto assess the effect of injurylevel on exerciseresponse and orthostatictolerance, participantswithcervical SCI and thoracicSCI were recruited. Amongstthese participants, individualswith ASIAincomplete and completeinjues were included.Individuals were noteligible for this studyif they hada documented history of cardiovasculardisease, uncontrolledhigh blood pressure,or injuries tomuscles, bones, ligaments,tendons or joints,respiratory illness,increased pain witharm activities, abrain injury which wouldstop them from understandingthe instructionsthat were given duringthestudy, or could not communicateEnglish. Individuals werealso excluded fromthe study if they andacute medical conditions(i.e., acute urinary tractinfection, pressure sores,etc.).Table 1. ParticipantcharacteristicsSubject No Age, yrHeight, cm Weight,kg Sex Lesion LevASIA Clas Time SinceInjurySCI139 18361 MC61C7 A142 32185.4 84.5M T6B 11339 157.563.9 FC61C7 B84 32180 72.5M C41C5B 135 32177.6 57.9F T4A 17633 182.988.2 MT4 A9Mean 34.5177.7 71.312.0SD 3.510.3 12.73.3AB133 168.868.2 M230 18379.5 M3 39161.9 66.1F4 31190.2 97.9M5 27165 60.6M6 38161.8 61.8FMean33 171.872.4SD 4.712.0 14.2134.1.1 RecruitmentParticipants withSCI were recruited primarilythrough the G.F.Strong rehabilitationcentre viaposter advertisementsthat were distributedand placed at thissite. Able-bodiedparticipants wererecruited from thestudent populationat the University ofBritish Columbia,and from the generalpopulation. Able-bodiedparticipantswere recruited viaadvertisements thatwere distributedandplaced at severalcommunal buildingswithin the universitycommunity (e.g.,student union building,eateries).4.2 General ProtocolThis was a prospective,controlled investigation.Each participant completedfour testing daysat the Cardiovascular Physiologyand RehabilitationLaboratory at theUniversity of BritishColumbia.Information on participants’height, weight,age, date of birth,and (for participantswith SCI) lesionlevel, time sinceinjury, and severityof SCI and ASIAscore were collectedon the first testingday(Table 1). Participantswith SCI wereasked to empty theirbladders to minimizethe influence of reflexsympathetic activationon peripheral vasculartone. On Test DayOne each participantsigned aninformed consentform outlining the experimentalprocedures andcompleted the PhysicalActivityReadinessQuestionnaire (PAR-Q)to ensure that participationin physical activitycould be permitted.Test Days One andTwo examined theeffects of rest on cardiovascularresponse tothe orthostaticstress, and assessedpeak oxygen uptakeduring hybrid exerciseand arm cyclingexercise. Test DaysFour and Five examinedthe effects of bouts ofsteady state armcycle and hybdexercise oncardiovascular responseto the orthostatic challenge.4.3 Orthostatic TestingParticipants underwentan orthostatic tolerancetest on all four testingdays. On the firsttwotesting days, participantsunderwent the orthostaticchallenge priorto performinga peak exercise test.On the final twO testingdays, participantsunderwent the orthostaticchallenge followinga bout of eitherarm or hybrid steadystate exercise.On each testingday, prior to undergoingthe orthostatic challenge,participants completeda fatigue scale110.While there is a knownlink between SCIand orthostatic hypotension9111,orthostatic stresstesting is not commonlyperformed in individualswith SCI becauseof the technicaldifficulties14associated with changes in posture. Orthostatic toleranceis usually evaluated using tilt table testing6.However, in persons with Sd, this requires extensive strappingto prevent buckling of the paralyzedlower extremities, which could potentially lead to autonomicdysreflexia. This would potentially maskorthostatic hypotension and invalidate any assessment oforthostatic tolerance in these individuals. Asimple bedside “sit up test” that has been developed was usedfor the evaluation of orthostatictolerance in this study6.This procedure requires minimal strappingand is sufficient to evaluateorthostatic cardiovascular control in persons with cervical and thoracic SCI6.Prior to testing days,participants were instructed to abstain from caffeine and alcohol, and exercise forat least 12 hours thenight before, and to consume only a light breakfast on testing days.While supine, participants were instrumented with an electrocardiogram (Pdwerlab16/30,ADlnstruments, Colorado Springs, CD) and a beat-to-beat blood pressuremonitoring device (Finapres;Ohmeda); the beat-to-beat blood pressure readings were verified with automatedblood pressurereadings. Stroke volume was measured via impedance cardiography (HIC-3000,Bio ImpedanceTechnology, Inc.) during the orthostatic challenge. Participants werealso instrumented with anultrasound probe to make transcranial Doppler (Companion Ill, Nicolet Vascular,SciMed Ltd., UK)measurements of blood flow velocity in the middle cerebral artery. Following15 minutes of supine rest,participants underwent a 15-minute passive orthostatic challenge (“situp test”6). Heart rate, strokevolume, cardiac output, and blood pressure were continuously monitored and recorded.4.3.1 Sit Up TestParticipants were positioned on the chair used to elicit the orthostaticchallenge in such a wayas to prevent and minimize slipping during the passive manoeuvre. To ensurethis, proper alignment ofparticipants’ hips and knees with the chair were made prior to thetest. Following instwmentation,baseline recordings were made during a 15-minute supine rest period.Participants were informedabout the importance of this test being passive and were instructed not to assistat all during the sit upprocedure6.Following the 15-minute supine rest pedod, participants werepassively moved into anupright seated position by raising the head of the chair and droppingthe base of the chair from theknees. This sit up position is essentially the same as when individuals are seatedin a wheelchair orchair, but the feet are not supported and the legs are freely dangling fromthe knees. This position wasmaintained for 15 minutes, during which time recordings were continued.This test was terminated15early and participants were returned tothe supine position if they experienced any symptomsofpresyncope (i.e., dizziness, lightheadedness,fainting, etc.).4.4 Testing Days One and Two (Randomized)Participants underwent an orthostatic stresstest followed by an assessment of oxygen uptakeand cardiac function during either peak armcycle or peak hybrid exercise, performingone of thesetests on each of these first two testing days(randomized). The orthostatic challengehas beendescribed previously. Arterial compliance wasalso assessed pre- and post-exercise on the firsttwotesting days.4.4.1 Peak Aerobic Fitness Testing Protocol(VO2peak Test)Prior to completing peak exercise testing, participantswere instructed to refrain from alcohol,coffee, tobacco, exercise, and food for at least12 hours. Participants performed twopeak exercisetests on two separate days separated bya minimum of 24 hours. Both testing days consistedof thecontinuous measurement of heart rate via electrocardiogram,heart rate variability (to assessautonomic tone), oxyhaemoglobin saturation(pulse oximeter), and the assessmentof arterialcompliance (applanation tonometry). Expiredgas and ventiliatory parameters wereacquiredthroughout the peak arm cycle and peak hybridexercise tests using a metabolic cart. This permitthedetermination of oxygen uptake and ventilation.Participants were asked to sit for five minutesbefore commencing the exercisetests andduring this time baseline measures of oxygenuptake, heart rate, blood pressure, andventilation werecollected. Additionally, at every second minuteof the rest period before commencingthe exercise test,and twice duñng each exercise stage(once during, and once at the end of each exercisestage),measures of cardiac output, stroke volume,total peripheral resistance, and arterio-venousoxygendifference were be assessed non-invasivelyutilizing inert gas rebreathing (acetylenerebreathe viamass spectrometry). Participants startedwith a five-minute warm-up at a self-selected cadence(between 50-80rpm) and power output to allowthem to become accustomed to theexperimental setupand the cycling. The peak exercisetests consisted of incremental exercise stageswhere power output(Watts) was increased until the participants reachedvolitional fatigue (i.e., participantswith SCI andable-bodied participants were not ableto maintain a cycling rate of approximately50 rpm, despite16maximal effort and verbalencouragement; thiswas verified in conjunctionwith their reported ratingofperceived exertion. Forall participants, the workloadwas increased from 5 to35 W per stage forthearms for both modes ofexercise. Exercise beganat a power outputfrom 10 to 30 W. Theresistanceat which participants startedthe exercise testsand the progressive increasesin power output duringthe successive stageswere determinedduring a brief familiarizationprior to commencingtesting.Exercise tests were terminatedimmediately if one or moreof the following symptomsoccurred: 1)tightness and/or pain inthe chest, 2) dizziness,lightheadedness,and/or nausea, 3) extremeshortnessof breath, 4) a significantdecrease in systolicblood pressure (> 10 mmHg),and/or 5) other abnormalelectrocardiogram responses,all of which may inferthe potential risk fora cardiovascular complication.A certified exercise physiologistwas present at alltests. Gas analyzers werecalibrated with gasesof aknown concentrationprior to each experiment.4.4.2 Peak Aerobic(VO2peak) Arm Cycle ExerciseTestingPartcipants with SCI satin the chair providedwith the hybrid exercisemachine (SCIFIT PROII,SCI FIT, Tulsa, Oklahoma)or in their own wheelchairswhich were positionedappropriately relativetothe exercise machine.Able-bodied participantssat in the chair providedwith the hybridexercisemachine. Participantswere seated in an uprightposition with the fulcrumof the handlebarsadjustedso that they were at shoulderheight. Follwing a five-minutewarm-up, the workloadwas graduallymade more difficultby increasing the intensityof each exercise stage.The test allowed fortheassessment of cardiorespiratoryresponse to peak arm exerciseincluding the determinationof peakoxygen uptake.4.4.3 Peak Aerobic(VO2peak) Hybrid Exericse TestingParticipants with SCIsat in the chair providedwith the hybrid exercisemachine (SCIFITPROII, SCI FIT, Tulsa, Oklahoma)or in their own wheelchairswhich were positionedappropriately relativeto the exercise machine.Able-bodied participantssat in the chairprovided with the hybridexercisemachine. Participantswere seated inan upright position with thefulcrum of the handlebarsadjustedso that they wereat shoulder height.An ideal seat height was setfor each individualso that the kneewas slightly flexedat full extension.All participants were ableto incorporate theirlegs into hybridexercise passively sincecycling the armsautomatically allowed forpassive cyclying ofthe lower limbswith the exercise machine.Participants’ feet werestrapped to the legpedals. Followinga five-minute17warm-up, the workload for thearms was gradually mademore difficult by increasingthe intensity ofeach exercise stage. There wasno resistance and theworkload was not increasedfor the lower limbssince they were passively incorporatedinto exercise (electricalactivity of the muscles ofthe right legwere monitored via electromyogramto try to monitor and minimizemuscle contraction ofthe lowerlimbs). This test allowed forthe assessment of cardiorespiratoryresponse to hybridexercise and thedetermination of peak oxygenuptake.4.5 Testing Days Three and Four(Randomized)As described previously, participantsunderwent the orthostatic challengeon all four testingdays. For Testing Days Threeand Four, participantscompleted a bout of eitherarm or hybd steadystate exercise prior to undergoingthe orthostatic challenge.Participants completed30 minutes ofcontinuous and moderate(65% of heart rate reserve) intensityarm cycle or hybrid exercise(randomized) followed immediatelyby a sit up test6 to evaluatethe effects of each mode of exercise(i.e., arm cycle and hybrid) onorthostatic response.4.6 Cardiovascular MeasuresOn all testing days, the followingmeasures were collected:heart rate (electrocardiogram),heart rate variability, ventilation,blood pressure (fingerplethysmography), oxyhaemoglobinsaturation,arterial compliance (applanationtonometry), cardiac outputand stroke volume (acetylenerebreathingand impedance cardiography),arterlo-venous oxygen difference,total peripheral resistance,and ratingof perceived exertion.For each participant, electromyogramdata was also collectedto monitor musclecontraction of the lowerlimbs during hybrid exercisein an attempt to minimizeit. On each testingdayduring the assessment of orthostatictolerance, blood flow velocityof the middle cerebralartery wasmeasured (transcranial Doppler).4.6.1 Middle Cerebral ArteryBlood VelocityBlood flow velocity ofthe middle cerebral artery wasmeasured using a CompanionIll transcranialDoppler system (CompanionIll, Nicolet Vascular, SciMedLtd., UK). A probewas fixed to thezygomatic arch of theparticipant and the probedirected ultrasound wavesat a frequency of 2MHzto adepth of 3.5 to 5.5cm. Bloodflow velocity was determinedapproximately atthe midpoint of the middlecerebral artery upstreamfrom the bifurcation tooptimize the ultrasoundwaveform. The ultrasound18probe was held in placeusing a transcranial Doppler fixationhead frame to ensure thevalidity of themeasurements. Both peak bloodflow velocity and mean bloodflow velocity (calculatedusing analgorithm which averages blood flowvelocity and mean bloodflow velocity over three second intervals)were taken.4.6.2 Arterial ComplianceThe non-invasive assessment of largeand small artery compliance wasbe performed prior toand immediately following peak exercisetests using an applanation tonometer(CR-3000, HDI) thatmeasures radial artery pulse waves. Radialarterial waveform acquisitionof the right arm was beobtained in conjunction with automatedblood pressure on the leftarm. This technology isa simple,convenient, and operator-independentmeans of evaluating vascularfunction and health, makingitparticularly appropriate for use withpersons with SCI.4.6.3 Blood PressureBeat-by-beat arterial blood pressurewas recorded via fingerphotoplethysmography (Finapres;Ohmeda) during the orthostaticassessment. Automatedblood pressure measurementswere alsoobtained to verify and correctthe readings obtained fromthe Finapres. Mean arterialpressure hasbeen calculated as [(systolic bloodpressure-diastolic bloodpressure)/3]+diastolic blood pressure.4.6.4 ElectromyogramElectromyogram was continuouslymeasured on muscles of the rightleg for all participantsduring the performance of hybridexercise, and a data acquisitionsystem (Powerlab 16/30,ADlnstruments, Colorado Springs,CC) and personal computerwere used to record thisdata. Theelectromyogram represents the combinedelectrical activity that is generatedby multiple actionpotentials of actively contractingmuscles112.4.6.5 Fatigue ScaleThe Lee Fatigue Scale11°was administered to obtain afatigue severity score. TheLee FatigueScale has been used to measureseverity of fatigue in healthyindividuals as wellas in clinical19populations113-115.This scalewas chosen to measurefatigue for this study becauseit is relatively shortand easy to administer. TheLee Fatigue Scale haswell-established validityand reliability1101164.6.6 Heart RateHeart rate was continuouslymeasured viaelectrocardiogram. A data acquisitionsystem(Powerlab 16/30, ADlnstruments,Colorado Springs, CC) anda personal computer wereused to recordheart rate and electrocardiogram.4.6.7 Heart Rate VariabilityHeart rate was monitored viaelectrocardiogram andsections of this data maybe visuallyexamined and analyzed. TheR-R intervals may beused to calculate heartrate variability, andcommercially availablesoftware used to analyzeit (Chart V5.02; ADlnstruments).4.6.8 Metabolic Cart andImpedance CardiographyExpired gas and ventilatoryparameters were acquiredthroughout the peakarm cycle andpeak hybrid exercise tests using amass spectrometer (Amis 2000,Innovision, Odense, Denmark),andthis permit the determinationof oxygen uptake. At the endof each exercise stage,measures ofcardiac output andstroke volume were assessednon-invasively usinginert gas rebreathing(massspectrometry) (Amis 2000, Innovision,Odense, Denmark). On testingdays involving assessmentoforthostatic tolerance, strokevolume and cardiacoutput were also measuredon a beat-by-beat basisduring the orthostatic challengevia impedance cardiography(HIC-3000, Bio-lmpedanceTechnology,Inc.).4.6.9 Oxyhaemoglobin SaturationOxyhaemoglobinsaturartion was continuouslymeasured non-invasivelyby a pulse oximeter(Ohmeda Biox 3740, Louisville,Colorado) placed on theear.4.6.10 Total PeripheralResistanceTotal peripheral resistancewas calculated as meanarterial pressure dividedby cardiac output.204.6.11 Rating of PerceivedExertionParticipants reported their ratingof perceived exertion immediatelyfollowing the endof eachexercise stage during peakexercise testing. Thiswas used as a means to evaluatethat exercise wasperformed to exhaustion. Priorto the exercise tests, there wasan explanation of therating ofperceived exertion scale beingused and any questions concerningthe procedure for rating theintensity of perceived exertionwere answered at this time. Participantswere asked to report theirrating of perceived exertion usingthe modified Borg scale117.215 STATISTICAL ANALYSISDifferences between measures of middle cerebralartery blood velocity, blood pressure,heartrate, stroke volume, cardiac output, arterio-venousoxygen difference, total peripheral resistance,arterial compliance, and rating of perceivedexertion between groups of participantsand mode ofexercise were examined using mixed modelanalysis of variance with Tukey posthoc comparisons.The level of significance was set a priori atp<0.05. Dataare presented as mean±SD.Additionally, to examine cerebral autoregulation,regressions of mean arterial pressureandmiddle cerebral artery blood velocity were examinedby plotting them against one another and fittingthem with a with a regression line. A coefficientof determination (R2) was considered physiologicallysignificant whenR2>0.75118.The coefficient of determinationprovides an index of autoregulatoryfailure, and the slope provides an index of theseverity of such a failure. The linear regressionswereobtained from a range of blood pressure valuesfrom the duration of the orthostatic challenge.Furthermore, in addition to the evaluationof the slope of the flow-blood pressure curve,the middlecerebral artery blood velocity correspondingto the maximal fall in mean arterial pressure wasalsoobtained to provide insights into the range of autoregulatoryresponses to the orthostatic challenge.The level of significance wasset a priori atp<0.05. Dataare presented as mean±SD.To analyze the difference in peak power outputbetween groups of participants and modes ofexercise, independent t-tests were employed.The level of significance was seta priori atp<0.05.Data are presented as mean±SD.226 RESULTSThere were no significantdifferences at baselinebetween any groups (able-bodied,Sd, andparaplegics and tetraplegics)for middle cerebralartery blood velocity,blood pressure, heartrate,stroke volume, and cardiacoutput. Additionally, therewas no significant differencein any of theaforementioned measureswhen comparing valuesat baseline and uponresuming the supinepositionfor all participants.6.1 Orthostatic Hypotension6.1.2 Middle CerebralArtery Blood VelocityParticipants with SCI (Figure1), and participantswith tetraplegia specifically,(Figure 2) did notexperience significantdecreases in middlecerebral artery blood velocity(MCABV) upon assuminganupright posture (64.39.0 to 55.9±7.9 cms-1,respectively)following a bout ofhybrid steady stateexercise. Paraplegicsdid not experienceany significant decreases inMCABV on any of the testingdays (Figure 3). Generally,across all testing days,MCABV increasedwhen participants returnedtothe supine position (60.1±1.5 to 66.6±2.7 and 57.8±3.5 to 61.4 3.0 cms-1,for able-bodiedparticipants and participantswith SCI, respectively).However, MCABVremained significantlyreducedin comparison to baselinevalues upon returningto the supine position followinga bout of arm steadystate exercisein participants with SCI(64.3±9 vs. 58.5±6.9 cms-1,respectively).Overall,examination of changesin MCABV revealed thatorthostatic responseswere affected bytheintervention that precededthe orthostatic challenge,with hybrid exercisepromoting improvedorthostatic responsein persons with SCI. Furthermore,able-bodied participants(Figure 4) showedless decrement toMCABV when assumingthe upright posture andgreater recoveryin MCABV uponresuming the supineposition in comparisonto the group with SCI. Acomparison of changesinMCABV between groupsduring the orthostatic challengeare illustrated inFigure 5.23•0EC)00•000a)I0a)I-a)0a)-o-DFigure 1. Middle cerebral arteryblood velocity during theorthostatic challengeinparticipants with SCI— Supi— Situp— Sup2100806040200Intervention prior to orthostaticchallengeChanges in middle cerebral arteryblood velocity in participantswith SCI during the orthostaticchallenge following rest,or either arm or hybrid steady stateexercise. The orthostaticchallengeincludes three segments:1) The baseline supine position (Supi),2) sit up (Sit up), and 3)thereturn to the supine position(Sup2).*p<O.05vs. baseline. Values aremean±SD.Rest ArmHybrid24•0)2C)2:’C)0I*— Supl— Situp— Sup2Figure 2. Middle cerebral arteryblood velocity duringthe orthostatic challenge inparticipants with tetraplegia120100806040200Intervention prior to orthostaticchallengeChanges in middle cerebral arteryblood velocity in participantswith tetraplegia during the orthostaticchallenge following rest, or eitherarm or hybrid steady state exercise.The orthostatic challengeincluded three segments: 1) Thebaseline supine position (SupI),2) the sit up position (Situp), and 3)the return to the supine position (Sup2).*p<O.05 vs. baseline.**p<O.O5 vs. sit up.Rest ArmHybrid25Figure 3. Middle cerebral artery bloodvelocity during the orthostatic challengeinparticipants with tetraplegia80EC)>‘C)00Intervention prior to orthostatic challengeChanges in middle cerebral artery blood velocityin participants with paraplegia duringtheorthostatic challenge following rest, oreither arm or hybrid steady state exercise. Theorthostaticchallenge included three segments: 1) The baselinesupine position (SupI), 2) the sit up position(Sit up), and 3) the return to the supine position(Sup2).6020— Supi— Situp— Sup2Rest Arm Hybrid26Figure 4. Middlecerebral arteryblood velocityduring theorthostatic challengein able-bodied individuals100SupISit upoSup2.. 80**0o600a)a)a)I...G)o200-______________Rest ArmHybridIntervention priorto orthostaticchallengeChanges in middlecerebral arteryblood velocity duringthe orthostaticchallenge in able-bodiedparticipants followingrest, or eitherarm or hybrid steadystate exercise.The orthostaticchallengeincludes threesegments: 1) Thebaseline supineposition (SupI),2) the sit up position(Sit up), and 3)the return to thesupine position (Sup2).*p<O.05 vs. baseline.27Figure 5. Middle cerebralartery blood velocityduring the orthostaticchallenge followingrest in participants120Changes in middle cerebralartery blood velocity duringthe orthostatic challengein able-bodiedparticipants, and participantswith paraplegiaand tetraplegia followingrest. The orthostaticchallenge includes threesegments: 1) Thebaseline supine position(Supi), 2) the sit up position(Sit up), and3) the return to the supineposition (Sup2).*p<O.05 vs. baseline.**p<O.05 vs. sit up.Regression analysiswas used to examinecerebral autoregulationin participants (Figure5).Previous findingshave illustrated that positiveflow-pressure correlationsand linear flow-pressurerelationships can be predicativeof autoregulation failurewith the slope of theregression indicatingtheseverity of the failure118.Able-bodied participantsdid not have any significantpositive correlation offlow to pressure, indicatingno failure of autoregulation.There was a similarfinding in participantswithSCI, except for oneparticipant with tetraplegiawho had a significantlypositive correlation followingabout of hybrid steadystate exercise. Thissuggests that, in this participant,cerebral autoregulationwasimpaired followinga bout of hybrid steadystate exercise. Whileno other participantswith SCI hadsignificant positivecorrelations, individualswith SCI generally had highercoefficients ofdeterminationin comparison to theirable-bodied counterparts,suggesting that thereis impairmentof cerebralautoregulation in persons withSCI. A negative slopeof the regression indicatesthat cerebralautoregulation is intact.This was illustratedby the correspondingchanges in blood pressureandmiddle cerebral arteryblood velocity inable-bodied participants.Upon assumptionof the upright— Supl— SitUp— Sup2**Able-bodiedParaplegic TetraplegicGroup28Figure 6. The flow-pressurerelationshipbetween the initialsupine positionand assumptionof the upright postureduring the orthostaticchallenge0 51015 20Maximal Change inMean Arterial Pressure (mmHg)Calculated regressionin participantswith SCI and able-bodiedparticipants formaximal changeinmean arterial pressureplotted against thecorrespondingmiddle cerebralartery blood velocityduringthe orthostatic challengeduring the transitionfrom the initialsupine positionto the assumptionof theupright posture.Data illustratedare following about of hybrid steadystate exercise. Therewere n 6for each of the participantswith SCI andable-bodied participants.Numbers indicatethe slope ofregression, if thecorrelation coefficientwas >0.75.posture, these participantsexperienced increasesin blood pressuredespite concurrentdecreases incerebral blood flow.The inverse responseof these two cardiovascularparameters is indicativeofintact cerebral autoregulation.Participantswith paraplegia alsoexhibited intactautoregulation sincethey had negativeslopes of regressionas well. The tetraplegicwith high correlation,on the otherhand, had a steepand positive slope ofregression followinga bout of hybrid steadystate exercise,suggesting thatcerebral autoregulationwas impaired inthis individual (Figure6). That is, uponassumption of the uprightposture, a declinein middle cerebralartery blood velocitywas accompaniedby a concurrent decreasein blood pressure.• sd• AB••‘U)22.16C)14o12m.10.- 80ci)C-)ci)Cci)200CC-2--U)-1000AB1.19••Sc’••I-529The changes in meanarterial blood pressureand MCABV followingassumption of the uprightposture (Figure 7 and Figure8, respectively) weremodest for persons withSCI and able-bodiedindividuals collectively, rangingfrom -2 to 18 mmHg,and 3 to 23 cms-’,respectively. The reductioninboth of these measureswas generally largerin participants withSCI in comparison toable-bodiedparticipants while thesedifferences were notstatistically significant.Furthermore, at the timewhenparticipants reachedtheir lowest mean arterialpressure during theorthostatic challenge,thecorresponding decreasein MCABV was generallysimilar across alltesting days, indicatingthatchanges in MCABV weresimilar between testingdays. However, followinga bout of hybrid steadystate exercise, individualswith SCI experienceda smaller decline in MCABVcorresponding to theirgreatest fall in mean arterialpressure (-5.4±4.3 cms-1 and -10.1±7.9 mmHg followinga bout ofhybrid steady state exercisevs. -8.6±6.1 cms-1 and -9.9±5.9 mmHg and -8.55.0 cms-1 and -8.8±6.8 mmHg followingrest and a bout of armsteady state exercise,respectively). Whenexaminingtetraplegics and paraplegicsspecifically, individualswith tetraplegiahad significantly greaterdecreasesin mean arterial pressure(-6.8±6.3vs.-12.9±4.7,-3.2±4.6vs. -14.4±4.8, and-3.6+12.2vs.-13.3±4.8 mmHg forparaplegics vs. tetraplegicsduring the orthostaticchallenge followingrest, and bouts ofarm and hybrid steadystate exercise, respectively)and MCABV (-5.9±3.2 vs. -11.4±8.2, -5.0±4.9vs. -12.0±2.9, and -3.1±5.0 vs. -5.9±6.1 cms-1 for paraplegicsvs. tetraplegics and theorthostaticchallenge following rest,and bouts of arm andhybrid steady stateexercise, respectively)thanparaplegics.30Figure 7. Temporalchanges in mean arterialpressure during theorthostatic challenge100906280=Cl)Cd)5 70C0)6050Time (mins)Able-bodied participants,and participants withparaplegia generallyhad similar changesin meanarterial pressurein response to the orthsostaticchallenge, while participantswith tetraplegia tendedtorespond in an oppositemanner. The formertwo groups experiencedincreases in mean arterialpressure upon assumingthe upright posture,and a subsequent declineupon resumingthe supineposition. Tetraplegicshad a decline in meanarterial pressure uponmoving to the uprightposition, andan increase whenreturned to the supineposition. Participantsmaintained the initialsupine (Supi), situp (Sit Up), and final supine(Sup2) position for15 minutes each.Data is from a representativeparticipant for eachgroup and represents cardiovascularresponse to the orthostaticchallengefollowing rest.0 10 2030 40 506031•ci)2C-)C)0a)>00ci).0ci)C-)a)00Able-bodied— —— ParaplegicTetraplegicSupi40 5060Figure 8. Temporalchanges in middlecerebral artery bloodvelocity duringthe orthostaticchallenge8070605040300 10 2030Time (mins)All participants experienceddeclines in middle cerebralartery blood velocityupon assumption oftheupright posture andan increase when returnedto the supine position.Participants maintainedtheinitial supine (Supi),sit up (Sit Up), andfinal supine (Sup2) positionfor 15 minuteseach. Data is froma representative participantfor each group andrepresents cardiovascularresponse to theorthostaticchallenge followingrest.6.1.2 Blood PressureWhen examining bloodpressure, participantswere differentially affectedby changes in postureduring the orthostaticchallenge. Specifically,for participants withSCI, blood pressureresponse wasaffected by lesion level.Able-bodied participantsexperienced increasesin systolic bloodpressure(SBP) upon assumingthe upright postureon all testing days (109.2±0.4 to 114.9±1.6 mmHg, acrosstesting days). When returningto the supine position, able-bodiedparticipants decreasedtheir SBP onall testing days (112.9±1.6 to 110.0±0.9 mmHg, across testingdays). Paraplegicsrespondedsimilarly to able-bodiedparticipants, whichwas illustrated by anincrease in SBP whenmoved to theupright position (110.2±2.3 to 113.6±4.1 mmHg, across testingdays), anda decrease in SBP whenthe supine position wasresumed (113.6±4.1 to 108.9±4.6 mmHg, across testingdays). The SBPresponse of tetraplegicswas opposite tothat of able-bodied participantsand paraplegics.They32EECd)Ci)a)000C.)0C’,Able-bodied— —— ParaplegicTetraplegicexperienceda decrease in SBP(across testing days)when assuming theupright posture (112.8±2.2to 107.0±4.1 mmHg), and anincrease in SBP (acrosstesting days) whenreturning to thesupineposition (107.0±4.1 to 109.9±3.6 mmHg). Changesin diastolic blood pressure(Figure 10) duringtheorthostatic challengewere similarto the changes found forsystolic blood pressure(Figure 9) duringtheorthostatic challenge.Overall, neither formof exercise appearedto differentially affectblood pressureresponse to the orthostaticchallenge.Figure 9. Temporal changesin systolic blood pressureduring the orthostaticchallenge14013012011010090800 10 2030 4050 60Time (mins)Able-bodied participantsand participants withparaplegia generallyhad similar changesin systolicblood pressurein response to the orthostaticchallenge, whileparticipants withtetraplegia tendedtorespond in an oppositemanner. The formertwo groups experiencedincreases in systolicbloodpressure upon assumingthe upright posture,and a subsequent declineupon resumingthe supineposition. Tetraplegicshad a decline in systolicblood pressure upon movingto the upñght position,andan increase when returnedto the supine position.Participants maintainedthe initial supine (Supi),situp (Sit Up), and final supine(Sup2) position for 15minutes each. Datais from a representativeparticipant for eachgroup and representscardiovascular responseto the orthostatic challengefollowing rest.33Figure 10. Temporal changes indiastolic blood pressure during theorthostatic challenge8070c)2260U)C,)ci)000cciC.)0C’,30Time (mins)Able-bodied participants and participantswith paraplegia generally had similar changesin diastolicblood pressure in response to theorthostatic challenge, while participantswith tetraplegia tended torespond in an opposite manner. Theformer two groups experiencedincreases in diastolic bloodpressure upon assuming the uprightposture, and a subsequent decline upon resumingthe supineposition. Tetraplegics had a decline in diastolicblood pressure upon moving to theupright position,and an increase when returned to the supineposition. Participants maintained the initial supine(Supi), sit up (Sit Up), and final supine(Sup2) position for 15 minutes each.Data is from arepresentative participant foreach group and represents cardiovascular responseto the orthostaticchallenge following rest.6.1.3 Heart RateUpon assuming the upright posture,able-bodied participants and participantswith SCI (bothparaplegics and tetraplegics) had significant increasesin heart rate (HR) after performingbouts of armand hybrid steady state exercise.The average values for HR (acrossgroups) were 60.9±6.8 to 67.6±6.9 and 59.0±4.7 to 66.4±6.7 beatsmin-1for arm and hybrid steady stateexercise, respectively.Upon returning to the supine position,both able-bodied participants andparticipants with paraplegiaand tetraplegia had significant decreasesin HR across all testing days(65.8±0.9 to 58.7±1.5, 68.9 +3.0 to 61.6±1.7, and 66.7±2.9 to 58.2±1.0 beatsmin-1,respectively). Generally,all participants0 10 20 30 4050 6034All participants experienced increasesin heart rate upon assumptionof the upright postureand adecrease when returned to the supineposition. Participants maintainedthe initial supine (Supi), situp(Sit Up), and final supine (Sup2)position for 15 minutes each. Datais from a representativeparticipantfor each group and representscardiovascular responseduring the orthostatic challengefollowing rest.experienced increases in HRupon assuming the upright posture,and decreases in HR whenreturningto the supine position (Figure11).Figure 11. Temporal changesin heart rate during theorthostatic challengeAble-bodied— —— ParaplegicTetraplegicSCl)Cci,ci)cciCcici)85807570656055500 10 20 30Time (mins)40 50 606.1.4 Stroke volumeWhen assuming the uprightposture, both able-bodiedparticipants and participantswith SCIexperienced significantdecreases in stroke volume (SV)on all testing days (57.3±11.6 to 56.3±8.6,76.3±11.4 to 56.5±9.5, and 80.8±1.9 to 56.8±10.4 mL, followingrest, and bouts of arm and hybridsteady state exercise, respectively,across groups). Similarly, uponresuming the supineposition, allparticipants had increasesin SV across all testing days(56.3±8.6 to 75.9±19.9, 56.5±9.5 to 78.3±19.9, and 56.8±10.4 to 75.1±16.7 mL, following rest, and boutsof arm and hybhd steady stateexercise, respectively, acrossgroups) (Figure 9). Similarly, paraplegicsand tetraplegics decreasedtheir stroke volume upon assumingthe upright posture. Whenreturned to the supine position,tetraplegics only increasedtheir SV significantly followinga bout of hybrid steady stateexercise (52.0±35All participants experienceddeclines in strokevolume upon assumptionof the upright postureand anincrease whenreturned to the supineposition. Participantsmaintainedthe initial supine(Supi), sit up(Sit Up), and final supine(Sup2) positionfor 15 minutes each.Data is froma representativeparticipantfor each group andrepresents cardiovascularresponse during theorthostatic challengefollowing rest.11.7 to 67.1±14.2 mL), andparticipants withparaplegia onlyafter a bout ofarm steady stateexercise(52.3±7.5 to 72.4±3.1 mL). Generally,on all testing days,all participantsexperienced decreasesinstroke volumeupon moving to theupright position,and increasesin SV towardbaseline whenthesupine positionwas resumed. Additionally,exercise did notdifferentially affectthe changes instrokevolume during theorthostatic challengebetween anyof the participants(Figure 12), thoughrecovery ofSV upon returningto the supine positionwas greater followinga bouts steadystate exerciseinparaplegics andtetraplegics (54.2±10.2 to 68.6±11.8 mL, acrossparaplegics andtetraplegics, andacross exercise mode),in comparisonto following rest(55.8±3.6 to 64.9 ÷ 5.7mL, across paraplegicsand tetraplegics).Figure 12. Temporalchanges in strokevolume duringthe orthostaticchallenge10090_______80-JS600C,,504030Able-bodiedParaplegicTetraplegic0 1020 3040 5060Time (mins)6.1.5 Cardiac OutputAfter assumingthe upright posture,both the able-bodiedgroup and groupwith SCI decreasedtheir cardiac output(Q) significantly on all testingdays (4.6±0.3 to 3.7±0.1, 4.6±0.3 to 3.7±0.04,36AU participants experienceddeclines in cardiacoutput upon assumptionof the upright postureand anincrease when returnedto the supine position.Participants maintainedthe initial supine(Supi), sit up(Sit Up), and final supine(Sup2) position for15 minutes each.Data is from arepresentative participantfor each group andrepresents cardiovascularresponse during theorthostatic challengefollowing rest.and 4.7 + 0.8 to3.8±0.2, following rest,and bouts of arm andhybrid steady stateexercise,respectively, acrossgroups) (Figure 10).When returning tothe supine position,able-bodiedparticipants had significantincreases inQ on all testing days. Participantswith SCI also increasedQafter returning to thesupine position, butthis increase wasonly significant followinga bout of armsteady state exercise (3.8±0.5 to 4.3±0.5 Lmin-1). Participants(able-bodied, paraplegics,andtetraplegics) generallyexperienced decreasesin Q when movedto the upright postureand increaseswhen returned to the supineposition (Figure13). The interventionperformed priorto the orthostaticchallenge did not appearto differentially affectchanges inQ significantly during the orthostatictest inparticipants with Sd.Figure 13. Temporalchanges in cardiacoutput duringthe orthostatic challenge87• 62-J.9-50C-)CDco4C)32Able-bodied— —— ParaplegicTetraplegic0 1020 30Time (mins)40 50606.1.6 Total PeripheralResistanceDuring the orthostaticchallenge on all testingdays, participantswith SCI and able-bodiedparticipants experienceda significant increasein total peripheralresistance (TPR)upon assuming the37upright posture,and a decrease inTPR when returnedto the supine position(Figure 14). The averagetotal peripheral resistance(across all testingdays and groupsof participants) whenmoving from thesupine to the uprightposture and thenreturning to the supineposition was 17.8±0.9 to 20.61±1.3 to16.9±0.6 mmHg•L-1min-,respectively.Generally, able-bodiedparticipants experiencedgreaterincreases in TPR whenmoved to the uprightposture than individualswith SCI. The averagepercentincrease (acrossall testing days) was5.3±13.8 % and 19.4±10.1 % for participantswith SCI andable-bodied participants,respectively.Figure 14. Temporalchanges in totalperipheral resistanceduring the orthostaticchallenge26-fl24222a)C)ci)Coa)a)a)0CD0I-22201816141210Across all groups, participantsexperienced increasesin total peripheralresistance uponassumption ofthe upright postureand a decrease whenreturned to thesupine position.Participants maintainedtheinitial supine (Supi),sit up (SitUp), and final supine(Sup2) position for15 minutes each.Data is froma representative participantfor each groupand representscardiovascular responseduring theorthostatic challengefollowing rest.6.2 Peak ExerciseTesting6.2.1 Power OutputBoth groups of participantswere able to exerciseto a greater peakpower output duringhybridexercise in comparisonto arm exercise (Figure15). Able-bodiedparticipants reachedsignificantlyAble-bodied— —— ParaplegicTetraplegic0 10 2030 4050 60Time (mins)38a)U)a)><Ui0a)-D0greater peak poweroutput in comparisonto tetraplegics duringpeak hybrid exercise(95.8±51.3 vs.21.7±11.5W, respectively) (Figure 16).Figure 15. Peakpower output acrossgroups duringincremental arm andhybrid exercise140120100806040200Peak power output wasgreater during hybridexercise in comparisonto arm exercise acrossall groupsof participants.Power Output (Watts)39Figure 16. Peak power outputduring incremental hybrid exercise160140120100- 800600a-40200*p<005vs. able-bodied.6.2.2 Peak Oxygen Uptake(VO2peak)Hybrid exercise resultedin significantly greater cardiorespiratoryrequirements throughoutincremental exercise in comparisonto arm ergometry in bothable-bodied individuals andpersons withSCI (Table 2). The averageVO2peak (across all groups) was 21± 9 vs. 19 ± 7 mLkg-1min-’, forhybrid exercise vs. arm ergometry,respectively (p <0.05).The cardiorespiratory responsesto hybridand arm exercise variedbetween groups. At higher exerciseintensities, able-bodiedindividuals had asignificantly higher oxygen uptakethan persons with SCI forboth modes of exercise(Figure 17). Theaverage VO2peak (acrossall modes of exercise) was 24.9±7.9vs. 15.7±4.2mLkg-1min-,for able-bodied participants vs.participants with SCI, respectively.Furthermore, personswith paraplegia hadsignificantly higher oxygenuptake than persons withtetraplegia with the averageVO2peak (across allmodes of exercise) was 18.5±3.7 vs. 12.9±2.4 mLkg-1min-,respectively.Able-bodied TetraplegicParaplegicGroup40Table 2. Cardiorespiratoryresponses topeak exercise testingMode of Exercise_______ArmHybridVariableAB SCIP TAB SCIP TVO2peak,23.6± 14.9± 17.3±12.5÷26.3± 16.5± 19.7±13.3±mLkg73*3.51.5*3.48.9*4.953*1.5*1minHRpeak, 146.8±134.2± 159.0± 109.3±153.7± 136.8±161±112.7±beatsmin-21.4*28.713.0*6.820.0*29.218.2*7.1SVpeak,83.9± 73.0± 71.3÷75.4±95.5±84.2± 83.2± 85.1±mL 12.712.3 10.022.1 13.116.5 22.513.1Qpeak,10.6± 9.5±2.9 10.8±7.6±2.6 13.1±10.1±12.1±8.2±2.4L•min-1 3.64.0a-12.5± 15.2±15.5± 14.7±12.2± 13,7±13.2± 14.2±VO2peak, 3.12.5t 2.4 3.62.0 6ff5.5 7.8mL021 OOmLblood*p<0.05 vs. tetraplegics.tp<0.05 vs. able-bodied.Values are means±SD.41Figure 17. Oxygen uptake for able-bodied participants,and participants with paraplegia andtetraplegia during incremental arm and hybrid exercisetests to exhaustion4035E30!2520E=150C)a,>‘x0503°25=02U)C0C)Ca)>Hybrid Exericse60* **80 10040 60 80 100Percentage of Peak (%)Oxygen uptake increased in all participantsduring peak arm and hybrid exercise tests. Able-bodiedparticipants and paraplegics had significantlygreater oxygen uptake than tetraplegicsduringincremental arm and hybrid exercise.*p<O.05 able-bodied participants vs. tetraplegics.**p<O.05paraplegics vs. tetraplegics.—s—- Tetraplegic Hybrid—0-— Paraplegic Hybrid—v—-- Able-bodied Hybrid* *** **0 20 404035Percentage of Peak (%)Arm Exercise—I-— Tetraplegic Arm* **—0—- Paraplegic Arm—v— Able-bodied Arm15* **10* **500 20426.2.3 Peak HeartRate, Stroke Volume,Cardiac Output,and Arterio-venousOxygen DifferenceHeart rate responsewas not significantlydifferent betweenparticipantswith SCI and theirable-bodied counterparts,nor between peakarm and hybridexercise (Figure 18).The average valueforpeak heart rate acrossgroups was 140.5±25.1 and 144.8±26.0 beatsmin-1forarm and hybridexercise, respectively.The average valuefor peak heart rateacross exercisemodes was 135±28.1and 150.2±20.1 beats•min-1for participantswith SCI and able-bodiedparticipants,respectively.However, heartrate was significantlydifferent betweenparaplegics andtetraplegics acrosstime duringboth modes of incrementalexercise. Paraplegicshad higher peakheart rate duringincrementalexercise than tetraplegics(159.0±13 beatsmin-1and 109.36.8, respectively,across testingdays).The average valuefor resting andpeak stroke volume(across testingdays and groups)was72.8 + 13.4 and84.6±15.3 mL, respectively).Stroke volumesignificantly increasedacross timeduring incrementalarm and hybridexercise in able-bodiedparticipants,and paraplegicsandtetraplegics, thoughthere were nosignificant differencesbetween any ofthe groups (Figure19).The average valuefor resting andpeak cardiac output(across exercisemodes and groups)was 4.2±0.7 and 10.5±3.4 Lmin-1,respectively.Cardiac outputincreasedsignificantly acrosstimeduring bothmodes of peak exercisein able-bodied participants,and participantswith paraplegiaandtetraplegia(Figure20). In the able-bodiedgroup and thegroup with SCI,cardiac outputwassignificantly higherduring incrementalhybrid exercisein comparisonto incrementalarm exercise(10.1±2.7 vs. 12.7 1-3.9, respectively,across groupsat peak exercise)(Figure 21).The averagevalue for restingand peak arterio-venousoxygen difference(across exercisemodes and groups)was 6.0±4.1 and 13.1+ 3.7 mL 02lOOmLblood-1,respectively.Arterio-venousoxygen differenceincreased significantlyacross time duringboth peak armand hybrid exercise(Figure22). Furthermore,individuals withSCI (both paraplegicsand tetraplegics)had significantlygreaterarterio-venousoxygen differencein comparisonto able-bodied participantsacross time andbothmodes of exercise(14.4±4.6 vs. 12.4±2.5 for participantswith SCI and able-bodiedparticipants,respectively).43Figure 18. Heartrate in able-bodiedparticipants, andparticipants withparaplegia andtetraplegia duringincremental armand hybrid exercisetests to exhaustion200Hybrid Execise*180—•— TetraplegicHybrid160 —0---Paraplegic Hybrid4-140C120100806040200________________________________________________I II0 2040 6080 100Percentage of Peak(%)200Arm Exericse180*—.—- TetraplegicAmi160 —0—- ParaplegicAmi- 140C120a 100806040200I0 2040 6080 100Percentage of Peak(%)Heart rate increasedin all participants duringincremental armand hybrid exercisetests to exhaustion.Able-bodied participantsand participants withparaplegia had greaterpeak heart rates forboth modesof exercise than tetraplegics.*p<O.05 paraplegicsvs. tetraplegics.44Figure 19. Strokevolume in able-bodiedparticipants,and paraplegics andtetraplegics duringincrementalarm and hybridexercise to exhaustion120Arm Exercise—-— Tetraplegic Arm—0-— ParaplegicArm100—v-— Able-bodiedArm0_4’O6’O8O1àOPercentage ofMaximum (%)Hybrid Exercise120Tetraplegic Hybrid—0—-Paraplegic Hybrid1:60—vbodiedHybrid40200I II I0 204060 80100Percentage of Maximum(%)Stroke volume increasedsignificantly (p<O.05)throughout incrementalarm and hybridexercise for allparticipants.45Figure 20. Cardiacoutput in able-bodiedparticipants,and paraplegicsand tetraplegicsduringincrementalarm and hybridexerciseto exhaustion16Arm Exercise*14——— TetraplegicArm12—0—Paraplegic Arm*1;Percentage ofMaximum(%)Hybrid Exercise2018*—I-—Tetraplegic Hybrid16—0—— ParaplegicHybrid*U:dHvid*Percentage of Maximum(%)Cardiac outputsignificantly(p<O.05) increasedthroughout incrementalarm and hybridexercise forallparticipants. Cardiacoutput wassignificantly higherduring hybridexercise incomparisonto armexercise.*p<005vs. baseline.46121086420-*Figure 21. Peak cardiacoutput acrossgroupsE-J0C-)Cu0*p<O.05 vs.arm exercise.ArmHybridMode of Exercise47Figure 22. Arterio-venousoxygen differencein able-bodiedparticipants, and paraplegicsandtetraplegics duringincremental armand hybrid exerciseto exhaustion000.0-JE0-JE00I00U)00>0I.a,—*—— TetraplegicHybrid—0—— ParaplegicHybrid—v—— Able-bodied HybridPercentage of Maximum(%)Percentage of Maximum(%)Arterio-venous oxygendifference is increasedsignificantly during bothmodes of exercisefor allparticipants.*p<O.05 paraplegicsvs. able-bodiedparticipants.**p<O.05 tetraplegicsvs. able-bodiedparticipants.Hybrid Exercise00.0-IE-IEa,C.,=a,0=a>x0U)0a,>Ia,* *** ****3020100•2000 20 4060 80 100Arm Exercise——— Tetraplegic Arm—0--- ParaplegicArm—v-- Able-bodied Arm* *** *** **0 20 4060 80100486.2.4 Rating of Perceived ExertionBoth participants with SCIand able-bodied participantsreported significantly increasedratingsof perceived exertion (RPE)during both peak arm andhybrid exercise tests (Figure23). The averagereported values for RPE (acrossboth groups) were 7.8±1.5 and 8.3±1.7 for peak arm andpeakhybrid exercise, respectively.There were no significantdifferences in reportedvalues of RPE betweenable-bodied participantsand participants with Sd,though able-bodied individualsgenerally reportedhigher RPE values at the completionof peak exercise testing(across both modes ofexercise) (8.7±1.1 vs. 7.5±I .8, for able-bodied participantsand participants with Sd, respectively).490G)><wa)ci)000)0ci)><w0a)00)CD0 2040 60% Power Output80 100 120Figure 23. Rating ofperceived exertionduring incremental exerciseto exhaustion for able-bodied participants,and paraplegicsand tetraplegics12Able-bodied*108642010864200 20 4060 80 100120% Power OutputParaplegics*500a)><LUa)C)a)00cnRating of perceivedexertion increasedacross both modesof exercise.*p<O.05vs. baseline.6.2.5 Fatigue ScaleNo significant differenceswere found whenexamining the answersto the questionsposed inthe fatigue scale(Figure 24). Therewere no differencesbetween testingdays or groupsof participantswhen comparingthe same questions.Tetraplegics10864200 2040 6080 100120% Power Output51Figure 24. Responseto questions inthe fatigue scale (acrossgroups)10— sdAB860)8Cl)4201 23A 3B4A 4BTime of Scale AdministrationResponse to questionson the fatigue scalewere not significantlydifferent acrosstesting days orgroups of participants.For time of fatigue scaleadministration(x-axis): I & 2 = rest;3A pre-armsteady state; 3B = post-armsteady state; 4A= pre-hybrid steadystate; 4B = post-hybridsteady state.6.2.6 Arterial ComplianceBoth groups of participantshad significant changesin small and largeartery compliance frompre- to post-peak armand hybrid exercise(Figure 22). Theaverage values,pre-and post-exercise,across exercise modeswere 7.3±0.2 to 6.8±0.5 mLmmHg x 100and 15.6±0.6 to 14.6±0.4mLmmHg-1x 10 forsmall and large arterycompliance, respectively)for participants withSCI.Conversely, theaverage values, pre-and post-exercise,across exercisemodes, were9.1±0.5 to 9.4±0.5 mL•mmHg-1x 100and 14.4±0.4 to 14.5 ÷ 1.1mLmmHg-1x 10,for small and largearterycompliance, respectively)for able-bodiedindividuals. Able-bodiedparticipants’changes in arterialcompliance weredifferent comparedto participants withSCI. Able-bodied participantsincreased, whileparaplegics andtetraplegics decreased,small artery complianceand large arterycompliance frompreto post- exerciseacross both modesof exercise.52><E2-JEci)C)E0C-)>‘ECl)=22-JSci)C-)CD0S0C)ci)-tU)0)CD-J— TetraplegicsParaplegics— Able-bodied****Figure 25. Arterialcompliance inparticipants withSCI and able-bodiedparticipants14Small Artery Compliance1210864202520151050Pre-Arm Post-ArmPre-Hybrid Post-HybridLarge—Artery ComplianceTeiraplegicsParaplegicsAble-bodied**Pre-ArmPost-ArmPre-Hybrid Post-Hybridof exercise.Arterial compliancepre- and post-armand hybrid exercise.*p<O.05vs. post, for correspondingmode537 DISCUSSIONThe present studydemonstrated thatchanges in middle cerebralartery blood velocity,heartrate, stroke volume,and cardiac output followedsimilar trendsin both able-bodiedindividuals andpersons with SCI, whileblood pressure responseto the orthostatic challengewas different whencomparing able-bodiedparticipants andparaplegics with tetraplegics.Additionally, bothgroupsexperienced significantchanges to severalcardiovascular measureswhen transitioning betweenstages of the orthostaticchallenge, and whileoverall group differencesmay not be significant,examination of differencesin some measures ofcardiovascular responsesuggest that cardiovascularcontrol not only differsbetween able-bodied individualsand individuals withSCI, but betweenparaplegics and tetraplegicsas well. A smallsample size likely limitedthe ability to find morestatistically significantdifferences betweenthe groups of participantsin this study, thoughclinicalsignificance and importanceof these findings shouldnot be overlooked.This is the first investigationto examine cardiovascularresponses to an orthostaticchallengefollowing an acutebout of steady state exercise.Exercise appeared tohelp individuals withSCIimprove their recoveryfollowing an orthostaticchallenge. Exercisetraining has been foundto have apositive effect on orthostatictolerance by promotingincreases in plasmavolume64119and overall bloodvolume’20whichmay be helpful since lowblood volume isassociated with orthostatichypotension121.Furthermore,several studies haveexamined cardiovascularresponse to an orthostaticchallengefollowing a singlebout of maximal exerciseand found that orthostatichypotension and intoleranceareameliorated122-126.Thisis expected since theshort-term impactsof maximal exerciseincludeexpansion or restorationof blood volume127128,and increased sensitivityof the carotid-cardiacbaroreflex’23124, 129-131Plasma volumemay expand followinga single bout of maximalexercise due tothe secretion of hormonesrelated to controlof fluid-electrolyte homeostasis,increased thirst, increasedplasma protein synthesis,and renal retentionof sodium and water132-137.Maximal exercisehas beenfound to help ameliorateorthostatic hypotensionin individuals withSCI via increasedvasoconstrictivereserve138.Thatis, the cardiovascularsystem remains vasodilatedin response toan increase in bloodvolume and centralvenous pressurewhich result followingexercise’39.Thisincreased vasodilationsuggests that thereis an increasedcapacity to vasoconstrictresulting froman increase in centralvenous pressureand plasma volume whichare subsequent to avasodliated cardiovascularsystemfollowing maximalexercise129.54Furthermore, exercisetraining improvessympathovagaltone in able-bodiedindividuals, whichhas been found to improveorthostatic tolerancein this population120.A shift in autonomicbalance inpersons with SCIwould likely help toameliorate symptomsassociated with orthostatichypotensionsince they experienceimpairment to theirautonomic nervoussystem followinginjury. Exercise alsohas the potentialto improve the myocardiumby enhancing its contractility140,and this, along withincreased preload,and reduced afterloadmay help to improve functioningof the heart. Thus,it hasbeen shown that exercisetraining hasthe ability to help resetthe relationship betweenautonomiccontrol and heart function(sympathovagal shift)120,and based onfindings of this investigation,it alsoappears as thoughan acute bout of steadystate exercise promotesimproved cardiovascularresponseto a subsequentorthostatic challenge.Light to moderate levelsof activity, such asthat performed duringa warm-up or recovery,havealso been foundto play an important rolein promoting venousreturn, and subsequentlyto maintainingan elevated strokevolume. That is, whenactive recovery isperformed insteadof passive recovery,individuals havebeen found to have improvedcardiovascular responsewhich is illustratedbyattenuated decreasesin stroke volume andcardiac output, andrestoration of elevatedheart rate topre-exercise restinglevels141.While recoveryfollowing bouts ofsteady state exercisewas notperformed in thisstudy, it may be postulatedthat for individualswith SCI, the moderate(65% of heartrate reserve) levelof activity may have promotedelevations in strokevolume by promotingvenousreturn. That is,the performance of alight to moderate levelof activity, in andof itself, may be sufficientto promote improved circulationand cardiovascularfunction in individualswith SCI, thus helpingtoimprove responseto an orthostatic stress,which is in agreementwith the findingsof this study.While acutebouts of steady stateexercise may helppromote improvedcardiovascularresponse to an orthostaticchallenge in individualswith SCI, othermechanisms for animprovedresponse are relatedto adaptations individualswith SCI undergosubsequentto injury. Peripheraladaptations may alsohelp individualswith SCI, specifically paraplegics,adapt to orthostaticintoleranceand overcome theeffect of vasomotordysfunction. During exercise,paraplegicsmay have a smallerdecrease in strokevolume than theirable-bodied counterpartsduring an equivalentorthostaticchallenge63,andwhile not a significantfinding in this investigation,a greater decreasein stroke volumewas observed in able-bodiedindividuals in comparisonto paraplegics followingbouts of arm andsteady state exercise.In individualswith paraplegia, venousdistensibility andcapacity are lowerand55venous flowresistance is higherin comparison totheir able-bodiedcounterparts97.142,resulting in lessblood pooling. Ithas been observedthat at an equivalentlevel of orthostaticchallenge the changeinvolume in the lowerlimbs of individualswith paraplegiais less than thatin able-bodiedpersons63.Asmaller reductionin stroke volumemay or may not result,but its occurrence,should it occur, canbeaccounted for bya reduction in venousdistensibility in theparalyzed lowerlimbs63,suggestingthat lessblood pools in thelower limbs of personswith paraplegia.An important considerationto make is that whileprevious studieshave examined theeffects ofexercise trainingon orthostatic hypotension,similar benefitsin cardiovascularresponse followingacutebouts of exercise mayexist as illustratedin this investigationby significant improvementsin strokevolume followingthe orthostatic challenge.This may suggestthat followingan orthostatic challengeina rehabilitative setting,persons withSCI may recoversome cardiovascularparameters moreeffectivelyif exercise is performedprior to undergoingan orthostatic stress.While this may notincrease toleranceto assuming an uprightposture, it mayhave an impact onthe level of discomfortexperiencedbyindividuals followingcompletion of thechallenge. This isimportant as it appearsas though evenanacute bout of exercisemay help to improverecovery143.Individuals withSCI also hadan improved cerebralblood flow responseto an orthostaticchallenge followinga bout of hybridexercise in comparisonto following restor a bout of armsteadystate exercise.Furthermore, middlecerebral arteryblood velocity remainedsignificantlydeclined incomparison tothe baseline valuewhen the orthostaticchallenge was performedfollowinga bout of armsteady state exercise.This suggests that hybridexercise performedimmediately priorto an orthostaticchallenge may bebetter able toattenuate the decreasein cerebral bloodflow velocity normallyexperienced byindividuals whenassuming the uprightposture. Possibleexplanations forthis findingare exploredby examining the rolecerebral autoregulationand the impact ofcardiovascularparameters.Cerebral autoregulationnormally ensuresthat cerebral bloodflow remains relativelyconstantdespite changesin blood pressure,provided meanarterial pressuredoes not exceedtheautoregulation range,which is normally50 to 170 mmHg144145Retention of cerebralblood flow duringchanges in arterialpressure is accomplishedby active constrictionduring higherpressures and dilationwhen there are declinesin pressure146.Significant correlationsbetween mean arterialpressure and56middle cerebral arteryblood velocityhave been found147-150,though this is not a universalcorrelation151-158However, it hasbeen found that, generally,mean arterial pressuremay be used torepresentcerebral perfusionpressure, and middlecerebral artery bloodvelocity is a reliableindex of cerebralblood flow159.It is also importantto note that changesin middle cerebral arteryblood velocity thataremeasured by transcranialDoppler are knownto be proportional to cerebralblood flow solong as thediameter of the middlecerebral artery remainsconstant152160-162That is, interpretationof an increaseor decrease in bloodflow velocity asa reflection of an increaseor decrease in flow,respectively, is alsodependent upon the assumptionof a constant diameterof the insonated vessel.It has been foundthatduring a variety of stimulithat are known toaffect cerebral bloodflow, the diameterof the middlecerebral artery changesminimally (<3.O%)162.163Participants inthis investigation remainedwithin theautoregulated range,suggesting that basedon the definition ofautoregulation andthe limits withinwhich is works,participants in this studywould be expectedto have the ability to relyon cerebralautoregulation to preventcerebral hypoprofusionwhen experiencinga reduction in bloodpressure.There was only oneparticipant with tetraplegiawho, following aboutof hybrid steadystateexercise, had a positivecorrelation betweenflow and pressure.This was not foundin any of the otherparticipants, suggestingthe presence of intactcerebral autoregulationin these individuals,aspreviously described.Tissues that autoregulatehave no, or only a weak,correlation of changein flowto a correspondingchange in pressure.In contrast, tissuesthat do not autoregulatehave a linearorcurvilinear relationship164-166.It has been deschbedpreviously that a linearrelationship existsbetweencerebral perfusionpressure andmean blood velocitybelow the autoregulatedrange while thepressure-flow relationshipbecomes progressivelymore linear with failureof autoregulation167.Intheupright posture, if systemicblood pressure decreasesto low levels, cerebralperfusion declinesevenfurther due to the verticalheight difference64.However, individualswith SCI have beenfound toexperience similardeclines in cerebral oxygenationas their able-bodiedcounterparts, despitegreaterfalls in systemic bloodpressure60.Thus,whether or not these individualsexperience of orthostatichypotensionmay be dependenton the amount of declinein cerebral bloodflow, which inturn mayaffect cerebral oxygenation,but this is still unclear9.While participants withSCI in this study generallyexperienced greaterdeclines in mean arterialpressure in comparisonto their able-bodied counterparts,their cerebral oxygenationmay not have beenreflected by parallelchanges in mean arterialpressure.Despite large changesin autonomic controland function following SCI,function of cerebral57autoregulation in participantswith SOt in thisstudy was similar to able-bodiedparticipants. However,there are other factorsthat may affect orthostatictolerance and responseto an orthostatic challenge.Similar to previous findingsin persons suffering fromorthostatic hypotension168,individualswith SCI may experiencean expansion of theautoregulated rangeat both the upper andlower limits,so that cerebral perfusionis able to remain relativelyconstant even duringan orthostatic challenge.While this may help individualswith SCI to manageorthostatic hypotension,participants with in thisstudy all remained within theautoregulated range,making an expansionof the autoregulatedrange inthese individuals unnecessary.Given that perfusion pressureplays a large role in cerebralblood flow, cardiacoutput is alsoexamined for its rolein cerebral autoregulation.A significant linearrelationship betweenmiddlecerebral artery bloodvelocity and cardiacoutput at rest and duringexercise has been previouslydemonstrated169.It is thought that cerebral bloodflow is modulated bycardiac output and thishasbeen demonstrated previouslywhere attenuationsin cardiac output,leading to decreasedperfusion,have been postulatedto attribute to a decreasein cerebral perfusion, whichmay lead to symptomsassociated with orthostatichypotension55.However,oxygen extraction hasnot been found tobe alimiting factor to meeting oxygendemands of the brain,implying that the brainis well-protected157.Thismay help to explain why thesingle participant withtetraplegia had a significantlypositive correlationbetween mean arterialpressure and middle cerebralartery mean blood velocity.Inspection of thisparticipant’s cardiacoutput during the orthostaticchallenge following about of hybrid steadystateexercise revealedthat it decreased, whenthe upright posture wasassumed during thetest, to a levelthat appearedto compromise this participant’sautoregulation. Thus,as there is a significantlinearrelationship betweenmiddle cerebral arteryblood velocity and cardiacoutput at rest, it maybepostulated thatthe improved responseof middle cerebral arteryblood velocity followinga bout ofhybrid steady stateexercise, as illustratedby the finding thatthe decrease in cerebralblood flow wasnot significant duringthe orthostatic challengeonly following a boutof hybrid steady stateexercise,may be attributed to thecorresponding significantincrease in cardiacoutput that was foundimmediately followingreturn to the supineposition. This correspondsto the finding of no significantdecreases in cerebralblood velocity followinga bout of hybrid steadystate exercise.58In contrast, the contributionof heart rateto cardiac outputin the regulationof cerebral bloodflow does not appearto have a significanteffect on middle cerebralartery blood velocity’70.Generally, all participantsresponded to theorthostatic stressas expected,with decreasesinmiddle cerebral arteryblood velocity, strokevolume, and cardiacoutput, and increasesin heart rate,which are consistentwith findings fromprevious studies118171-173However, there weredifferences inblood pressure responsebetween groups.Individuals withparaplegia respondedin a similar mannerto able-bodied persons,while tetraplegicsresponded inan opposite manner.Additionally, participantsexperienced an increasein total peripheralresistance upon assumingthe upright posture.Changes inmean arterial pressureare often assumedto reflect changes incardiac output174,but this has onlybeen illustrated duringacute changes incardiac output.This linear relationshipwas not apparent inparticipants duringthe orthostatic challengeand the relationshiphas not been foundto be linear afterashort period of time(15 seconds)174.Accordingly,to limit changes tomean arterial pressuredespitedeclines in cardiacoutput, total peripheralresistance increased.Differences in cardiovascularcontrol and functionof the autonomicsystem between able-bodied individualsparaplegics and tetraplegicsaffected cardiovascular,specifically bloodpressure,response to theorthostatic challengein this investigation.Upon moving tothe upright and seatedposition, able-bodiedindividuals and paraplegicsincreased theirblood pressureto counteract themovement andsubsequent poolingof blood in the lowerlimbs. However,persons with tetraplegiaexperienced decreasesin blood pressureupon assuming theupright posture, whichis in agreementwith findings fromother studies55173This is expectedas previously mentioned,since individuals withtetraplegia are morelikely to experienceorthostatic hypotensionbecause thebalance betweentheparapsympatheticand sympathetic nervoussystem is alteredto a greater extentin persons withcervical and highthoracic injuries9.Overall, whilethe examinationof cardiovascular parametersreveals interestingand uniqueresponses to anorthostatic challengein participantsin this study, it isalso interesting tonote thatparticipants withSCI did not appearto experienceany discomfort relatedto symptoms associatedwithorthostatic hypotension,which was reflectedby responsesto the questions posedin the fatiguescaleand no reports ofdiscomfort duringthe orthostatic challenge.This may be relatedto time since injuryfor persons withSCI. In individualswith chronicorthostatic hypotension,mean arterial pressurehas59been found to remainwithin the autoregulatedrange118.Accordingly,since only individualswithchronic injuries (>oneyear) were includedin this investigation,it may be postulatedthat this affectedcardiovascular responseto the orthostatic challengein comparisonto the responses that wouldhavebeen seen in individualswith acute injuries.The length of sustainedinjury may be a factorthatdifferentiates severalphysiological responsesin persons with SCI,including orthostatictolerance.Individuals who havea recently sustainedSCI are knownto have lower blood pressureand higherheart rate than thosewith long-standinginjuries50.Individualswith acute injuriesare also moresusceptible to orthostaticchanges in blood pressureand experience morehypotension-relatedsymptoms50.As the lengthof time since injuryincreases, accommodationto an upright postureis alsoenhanced50.Studiesthat include individuals withboth acute and chronicinjuries50 have founddifferences in the abilityto tolerate inducedhypotension.Participants with chronicinjuries are betterable to tolerate tiltingat various degrees. Theyelicit fewer symptomsof orthostatichypotension, andhave less pronouncedblood pressureand heart rate responsewhen tilted to theverticalposition5o.This may helpto explain the toleranceobserved in participantswith SCI in this studysince they all hadlongstanding injuries.Furthermore, responsesto the fatigue scaledid not reveal any significantdifferences betweenany of the groups ofparticipants or betweenany of the testingdays and times atwhich it was administered.This suggests thatin individuals with chronicSCI, fatigue, as assessedbythe scale, does notlend itself to associationswith cardiovascularresponse to anorthostatic challenge,though this may notbe the case for personswith acute SCI.Furthermore, itappears as thoughpersons with chronicSCI do not reportgreater fatigue severityin comparisonto their able-bodiedcounterparts, asillustrated in this studysince participants withSCI did not report,like the able-bodiedparticipants, any discomfortduring or followingthe orthostatic challenge.The lack of statisticalsignificance toindicate increasedtolerance to orthostaticstress as revealedby cardiovascularparameters measuredin this study is likelythe consequence ofa limited number ofpersons with SCIwho participated inthis investigation,as generally, cardiovascularresponses to the orthostaticchallenge were similarbetween individualswith SCI and their able-bodiedcounterparts,except forparticipants withtetraplegia, since theirautonomic control andbalance followinginjury is alteredto adifferent extent in comparisonto paraplegics.As illustrated by thefindings of thisstudy, cardiorespiratoryresponse to exercisewassignificantly differentbetween able-bodiedindividuals and personswith Sd. Additionally,theresponses to peak armand peak hybrid exercisewere different forboth groups and exercise60performance and capacitywere different betweenthese two groups.In agreement with previousstudies comparinghybrid to arm cycleexercise77-79,resultsof the current investigationillustrate thatexercise incorporatingthe upper and lowerlimbs elicited greatercardiorespiratory responseincomparison to armexercise alone in bothable-bodied individualsand persons withSCI. Furthermore,findings of this study demonstratethat the passive inclusionof the lower limbsinto hybrid exercisewasan effective meansto promote enhancementsin aerobic performancein comparisonto arm exercisealone. This novel findingsuggests that activemuscle contractionwas not necessaryto enhanceexercise capacity, whichis beneficial for individualswith SCI, who commonlyexperience lowerlimbparalysis following injury.Previous investigationsthat have examinedthe effects of passiveinclusionof the legs during exercisefor persons with SCIhave demonstratedan improvement incardiorespiratory response41-44.It has been found thatpassive cycling movementsare effective inpromoting circulationin passively movedmuscles in both able-bodiedindividuals44and individualswithSC141.Thus, the passiveincorporation ofthe legs along withactive movement ofthe upper limbs hasthe potential to enhancecardiorespiratoryresponse even further,as combined activityof the arms andlegs utilizes a greater volumeof muscle than eitherarm or leg exercisealone, and has beenfound topromote enhancementsin aerobic capacity82.The improvements in cardiorespiratoryresponse withthe inclusion of passiveleg exercisemay be attributed to rhythmiclengthening and shorteningof theleg muscles, specificallythe paralyzed musclesin individuals withSd, which helpsto promote venousreturn during activity41.Venous return in able-bodiedindividuals is promotedby active contractionof the legs and theability to activate theskeletal muscle pump.Contractions of theleg muscles providepressure againstthe veins and help thevenous valves returnblood to the heartand central circulation8384.Whileindividuals with SCIcannot actively contractthe muscles of theirlower limbs, the findingin this studythat passive activityof the legs is ableto help promote greatercirculation helpsto explain theenhanced cardiorespiratoryresponse to hybrid exerciseversus arm exercise.An increase in venousreturn leads to anincrease in cardiac fillingand preload, and ultimately,an increase in strokevolume4278, 175,all of which enhance cardiorespiratoryresponse and exerciseperformance.Furthermore, the useof a greater volumeof muscle during hybridexercise in comparisontoarm exercise alonemay have helped individualswith SCI increaseexercise. Exercisethat uses moremuscle enhancesaerobic demand andcapacity becauseof the greater stressthat is placed on the61central cardiovascularsystem to delivera larger amountof oxygenated bloodto active muscle82.Thegreater aerobiccapacity found followinga bout of peak hybridexercise in comparisonto peak armexercise supports thatidea that there isa linear relationshipbetween theamount of activemusclemass and aerobic performance176.As expected, aerobicperformance wassignificantly higherin able-bodied individualsincomparison to individualswith SC!, and higherin paraplegics thantetraplegicsand this is the resultofdifferences in autonomicfunction and controlbetween these groups.Differences in performancearerelated to greatercardiovascular functionand controlas illustrated by greaterheart rate, strokevolume,cardiac output, andoxygen uptakein able-bodied individuals.However, the factthat able-bodiedindividuals are ableto actively contracttheir leg musclescannot be disregarded.Even though muscleactivity in the lowerlimbs was monitoredduring hybrid exercise,visual inspectionof this recordingrevealed that able-bodiedparticipants hada difficult time completelyrelaxing theirlegs and havingthem fully incorporatedinto exercise passively.This lends itselfto the possibilitythat the exerciseperformance of able-bodiedpersons inthis study was overestimatedsince some participantsmay haveused their legs toincrease exerciseperformance, enhancingtheir peak oxygenuptake beyondwhatthey would be ableto reach if theability to use theirlegs was restricted.Incorporating thelegs activelyinto exercise isable to enhancecardiorespiratoryresponse by increasingvenous returnvia activationof the skeletal musclepump83 . However,this does not refutethe finding in thisstudy that whole-body exercisepromotes greatercardiorespiratoryresponse in comparisonto arm exercisealone, andthat aerobic fitnessand capacity is greaterin able-bodied individualsin comparisonto persons withSC!.An examinationof peak heart rate responseto both modes ofexercise also revealsinformationabout the impactof lesion level onexercise capacityand about theeffects of differentmodes ofexercise on cardiorespiratoryresponse. Impairmentsof the autonomicnervous systemfollowing SCIleads to changesin cardiovascularcontrol. There isa decrease in sympathetictone below the lesion177, 178Previous studies haveshown that maximalpower output,maxima! oxygenuptake, and totalwork is higher inathletes with lowerlesion levels106.Thisis in accordancewith the findingsof thisstudy as individualswith paraplegiahad greater valuesfor peak heart rateduring both modesofexercise in comparisonto tetraplegics. Furthermore,during exercise,it has been foundthat higherlesion levels produceblunted cardiorespiratoryresponses toexercise in comparisonto persons with62lower levels of SCI. Whetherat rest or during submaximalor maximal levels of exercise,individualswith tetraplegia, in agreementwith the findingsof the present study, havebeen found to have lowervalues for oxygen uptake,heart rate, work rate,and ventilation in comparisonto paraplegics96107108Individuals with higherlesion levels may havemore paralyzed musclefollowing injury aswell asgreater interruptionto sympathetic pathways incomparison to individualswith lower lesionlevels107108This also corresponds with thefinding in this investigationthat individuals with paraplegiahave similarcardiovascular responsesto exercise as their able-bodiedcounterparts since individualswith lowerlevel lesions are likelyto have less impairmentto their autonomic nervoussystem, subsequentlydecreasing cardiovascular limitationsto exercise performance.In agreement with this,individuals withparaplegia had greaterheart rate response toboth modes of incrementalexercise in comparisontotetraplegics. In additionto differences observed forpeak heart rate, a correspondingfinding for peakpower output was foundin this investigation. Thatis, able-bodied individualswere able to reach asignificantly greater peak poweroutput than participantswith tetraplegia during hybridexercise, andthis difference was closeto being statistically significantfor arm exercise.Furthermore, peak heart ratetended to be higher duringhybrid exercise in comparisonto armexercise. This suggeststhat exercise capacity is greaterduring whole-body exerciseand both personswith SOt and able-bodiedindividuals are able toenhance exercise performanceby concurrently usingtheir arms and legs, sinceheart rate is able to increaseto a greater extent, andthis has been shownpreviously in able-bodiedindividuals and personswithSC1179.While central factors appearto help augment exercise capacitywhen the legsare incorporatedinto exercise, peripheralfactors are also importantto consider. While cardiacoutput may increase inresponse to a greaterneed for oxygen at thelevel of the muscle duringhybrid exercise in comparisonto arm exercise, peripheraloxygen extraction maybe elevated due to theactivation of a greater volumeof muscle mass79180Interestingly, arterio-venousoxygen difference duringexercise was significantlyhigher in individuals withSCI in this study. Whilethere were no significantdifferences between armand hybrid exercise, it may bepostulated that performanceof hybrid exercise helpedto improve thisparameter in the participantswith 501. While persons withSCI generally experiencebluntedcardiorespiratory responseto exercise, the factthat oxygen extraction maybe increased to an extentgreater than that foundin their able-bodied counterpartsis worth examining. Asillustrated in this study,cardiac output increaseswith exercise, in agreementwith previous findings41,leading to an enhanced63capacity for oxygendelivery duringactivity. However,in individuals with SCI,alternations tothenervous system followinginjury affect theresponse of the centralnervous systemto exercise. Thismay limit effective redistributionof blood sincethe ability to contractthe muscles ofthe lower limbs,which is lost due toparalysis following injury,promotes improvementsin cardiorespiratorymeasures,including, but not limitedto, cardiac output80181, 182Accordingly, personswith SCI havebeen found tohave lower stroke volumesand cardiac outputsthan their able-bodiedcounterparts69which is inagreement with thefindings of this studyfor paraplegics andtetraplegics andwas seen during theorthostatic challenge(Figure 13). Thus,elevated oxygenextraction may serveas a compensatoryresponse and has thepotential to enhancecardiorespiratory responseto exercise inpersons with Sd.Future studies examiningarteño-venous oxygenextracon are warrantedto support the findingsof thisstudy and determine whetherwhole-body exercisepromotes greaterimprovements in oxygenextraction in comparisonto arm exercise alone.It has been postulatedthat peripheral oxygenextraction may beelevated due tothe activation ofa greater volume of musclemass79183Additionally, a loweroxygen extractingcapacity has been reportedfor the arms’84-’87and evenfollowing training,only marginal improvementsin oxygen extractionby the arms havebeen observed.In contrast, it has beendemonstrated inseveral studies thatexercise in thepopulation with SCIthatincorporates the lowerextremities helpsto promote enhancementsin oxygen extraction42777888,inaddition to improvementsin cardiac output42’Similarly, it hasbeen found that followingtraining inable-bodied individuals,exercising musclemay require less bloodflow for the same submaximalexercise intensityas a result of anincrease in arterio-venousoxygen difference’.The lower oxygenextraction for thearms is associated witha lower oxygen conductancein the upper extremitiescompared with thelower extremities.Accordingly, fora given oxygen demand,a greater oxygendelivery is requiredfor exercising arm thanleg muscles,causing a relativelyhigh blood flowto theupper extremities’89.However, followingendurance exercisetraining in the generalpopulation, anincrease in total vascularconductance, andthe associated deliveryof more blood to exercisingmuscles, has beenfound to be primarilyresponsible for enhancingoxygen extractioncapabilities190.The result of this isa larger pressuregradient for enhancingthe deliveryof available oxygentoexercising muscle181.Thus, it can be postulatedthat exercise trainingincorporating thelowerextremities in personswith SCI may helpto promote enhancementsin central as wellas peripheralphysiological adaptations’81.64Participants reportedratings of perceivedexertion that indicatedthey perceived exerciseto bevery difficult atthe highest power outputthey attained, suggestingthey had exercisedto volitionalfatigue. This also indicatesthat participantssubjectively experiencedgreater levels of strainwithincreasing intensityduring exercise191 asmeasured by thescale. Able-bodiedindividuals tendedtoreport greater ratingsof perceived exertionat the completion ofpeak exercise testing.In agreementwith the cardiovascularmeasures collectedduring the peakexercise tests, able-bodiedindividuals alsosubjectively illustrateda greater work capacityin comparisonto persons with SCIby reporting higherlevels of strain expressedby greater ratings of perceivedexertion. Accordingly,this scale hasbeenfound to correlateand relate to a varietyof physiological measures,and has beenproven to be a validmeasure of exerciseintensity192.In agreement with previousfindings193,able-bodiedindividuals were foundto have higherarterial compliancethan persons withSCI. Inactivity resultingfrom paralysis andthe loss ofsupraspinal sympatheticvascular control havebeen reportedto be potential factorsfor poor arterialcompliance’94.Furthermore,arterial stiffness is associatedwith cardiovasculardisease, specificallyatherosclerotic burden193and arterial compliancedecreases as the severityof atherosclerosisincreases195.Participation in exercisehas been shownto increase arterial compliance196and arterialcompliance has alsobeen found to increasefollowing an acutebout of exercise197.Decreased arterialcompliance and increasedarterial stiffness maybe the result ofa variety changesto arterial structureincluding smoothmuscle hypertrophy, replacementof viable cells withconnective tissue,and increasedcross-linking of connectivetissue198.Exercisetraining, or moderatephysical activitymay help tomodify these changesin several ways:1) an increase in arterialpressure and heartrate may produceforces on the largeconducting vesselswhich may causethem to deform. Theresulting stretch fromoccasional periodsof increased deformationof the large blood vesselsmay combat some oftheconnective tissuecross-linking’98,2)vasodilation of skeletalmuscle increasesgreatly during exercise,and at least someof this is propagatedupstream to the largeconducting vessels198,and 3) an increasein pulsatile flowin the aorta during exercisemay lead to a greaterproduction ofvasodilating factors’99-201,including nitric dioxide,which relaxes vascularsmooth muscle inconducting arteries’98.However,arterial compliancewas not found to increasefollowing exercise inparticipants withSCI in this studyand several reasonsmay be postulatedto explain this. A changein body compositionfollowing injury65with a propensity towardsmuscle wasting and fataccumulation38is commonfollowing SCI andalongwith decreased physicalactivity following injury,increases the riskfor cardiovasculardisease38193Improvement in arterialcompliance following anacute bout of exercisewas demonstrated inobeseindividuals who were placedon a energy-restricteddiet to promote weightloss202.It has beendemonstrated in previousstudies that weight lossimproves arterial compliance203204Accordingly,perhaps individuals withSCI in this study werenot found to haveimproved arterial compliancefollowing exerciseas a result of greater fataccumulation subsequentto injury. That is, perhapsachange in body compositionwith an increase in leanmuscle mass and reductionin fat may help toimprove arterial compliancein this population. Additionally,it has been shown ina previous study thatsmall artery complianceincreases after an acutebout of exercise onlyafter six months of exercisetraining197.Accordingly,exercise trainingmay be required to help improvearterial compliance followingacute bouts of activity inpersons with Sd.While findings of the currentstudy show that acute formsof exercise do nothelp improvearterial compliancein persons with SCI, itis still important to notethat exercise rehabilitationhas beenfound to lead to markedhealth benefits in personswith Sd, and improveexercise tolerance67.Additionally, since arterialcompliance is a measureof cardiovascularhealth67,helping individualswithSCI to lead more physicallyactive lifestyles is important.668 LIMITATIONS AND FUTURECONSIDERATIONSThe small sample size for bothgroups of participants limited thestrength of some statisticalfindings of the present study andmay limit the generalizability ofthe findings. However, despitethissmall sample size, significant resultswere still found for several importantcardiovascular andcardiorespiratory measures in responseto the orthostatic challenge and peakexercise, respectively.Differences between groups of participantswere also revealed. Several studiesexamining exerciseresponse in individuals with SCIhave had sample sizes rangingfrom five to eight participants28294177.79, 205 206and have found statistical significanceand drawn upon both statisticallyand clinicallysignificant results to explain their outcomes.This is similar for studies investigatingorthostatichypotension in persons with SCI, whereseveral studies have sample sizesranging from five to eight50’63, 109, 207participants. Furthermore, withinthe group of participants withSCI, the number of individualswith paraplegia and tetraplegia(n=3 for both groups, respectively)is also small and likely limitedtheability to find more significant results andmake more generalizationsabout differences betweenthesetwo groups. However, differencesin autonomic functionand control following injury werereflected innumerous findings, keeping in agreementwith the fact that exercise capacityand response aredifferent between these individuals.This highlights the importanceof understanding variations incardiovascular responseto different stresses that are encounteredsince they may affect performance,whether during exercise,or another type of cardiovascularstress, such as an orthostaticchallenge inpersons with SCI.Ventilation, and thus, end-tidalor arterial, carbon dioxide were notmeasured during theorthostatic challenge and, therefore,the influence of chemoreceptorsensitivity and the retentionofcarbon dioxide on cerebral bloodflow dynamics were not assessedduring this test. For futureconsideration, measurementof ventilation would provide moreinformation about cerebralautoregulation during thesit up test in both able-bodied individualsand persons with SCI. It is currentlyunknown if the orthostaticchallenge employed in this studywould lead to hyperventilation whichhasbeen seen previously during head-uptilt. This has been found to alterthe partial pressure of carbondioxide and transcranial Dopplerrecordings of mean flow velocityin normal subjects208.Measuringventilation is an important considerationfor future studies sincethe partial pressure of carbon dioxideappears to be the most importantcontributing factor to cerebralblood flow regulation209210Numerousstudies have examined cerebralblood flow during an orthostaticchallenge and there arebothinvestigations that do118171,and donot172,211include methods to measurecarbon dioxide to assessits67influence on cerebralblood flow duringthe orthostatic stress.Additionally, whilethe partial pressureofcarbon dioxidehas been shownto regulate cerebralblood flow, it hasalso been illustratedthatchanges in cerebralblood flow areminor (3.9—4.4.%per Torr) in responseto hypercapnia212-215.While the partialpressure of carbondioxide duringan orthostatic challengein individuals withSCI has beenexamined55,thereare no currentinvestigationsthat explore thisduring an orthostaticchallenge followingan acute bout ofsteady state exercisein persons withSCI. Additionally,there areonly a limited numberof studies thathave examinedthe effects of exerciseon orthostatichypotension11,so further investigationis warranted.While personswith SCI in thisinvestigation includedtheir legs passivelyinto hybrid exercise,itwas observedthat passive inclusionof the lower limbsfor able-bodied individualswas a challenge.Even though activityof the legs duringhybrid exercisewas monitored viaelectroymyogram,and verbalfeedback wasprovided to participantsto encourage noactive movementof the legs, visualinspectionof electromyogramdata indicated thatable-bodied participantshad difficulty minimizingactive musclecontraction. Thus,it is difficult to definitivelyconclude thatpassive inclusionof the legs during hybridexercise in thisinvestigation promotesgreater cardiorespiratoryresponse in comparisonto armexercise alonein able-bodied persons,but the findingsof this studysupport the ideathat whole-bodyexercise promotesgreater aerobiccapacity andperformance inboth groups ofparticipants.Furthermore,it was illustratedin this study that passiveinclusion of thelower limbsduring exercise inpersons with SCIpromotes greatercardiorespiratoryresponse in comparisonto arm exercise alone.Finally, only individualswith chronic SCIwere included inthis study. Accordingly,it would bebeneficial to studythe effects ofan acute boutof steady state exerciseon responseto an orthostaticchallenge inpersons with acuteSCI, as toleranceto orthostatic stresshas been foundto change withincreasingtime since injury50.689 REFERENCES1. Mathias CJ, Frankel HL. Cardiovascularcontrol in spinal man. Annu RevPhysiol. 1988;50:577-592.2. Cariga P, Ahmed 5, MathiasCJ, Gardner BP. The prevalenceand association of neck (coathanger) pain and orthostatic (postural)hypotension in human spinal cordinjury. Spinal Cord.2002;40:77-82.3. Krassioukov A, Warburton DER,Teasel) RW, EngJJ. Orthostatic hypotension followingspinalcord injury. In: Eng JJ, Teasell R,Miller WC, et al, eds. SpinalCord Injury Rehabilitation Evidence.2006:1-17.4. Duschek 5, Weisz N, SchandryR. Reduced cognitive performanceand prolonged reaction timeaccompany moderate hypotension.Clinical Autonomic Research.2003;1 3:427-432.5. Amecan Autonomic Society and AmericanAcademy of Neurology. Consensusstatement onthe definition of orthostatic hypotension,pure autonomic failure and multiplesystem atrophy.Neurology. I 996;46: 1470.6. Claydon VE, Krassioukov AV.Orthostatic hypotension and autonomicpathways after spinal cordinjury. J Neurotrauma. 2006;23: 1713-1725.7. lllman A, Stiller K, WilliamsM. The prevalence of orthostatichypotension during physiotherapytreatment in patients with an acutespinal cord injury. Spinal Cord.2000;38:741-747.8. Figoni SF. Cardiovascularand haemodynamic responsesto tilting and to standing in tetraplegicpatients: A review. Paraplegia. 1984;22:99-109.9. Claydon VE, Steeves JD, KrassioukovA. Orthostatic hypotension followingspinal cord injury:Understanding clinical pathophysiology.Spinal Cord. 2006;44:341-351.10. Tederko P, Limanowska H,Krasuski M, Kiwerski J. Problemsof adaptation to wheelchairinearly stage rehabilitation after spinalcord trauma. Ortopedia TraumatologiaRehabilitacja.2006;8:672-679.11. Lopes P, Figoni SF, PerkashI. Upper limb exercise effect ontilt tolerance during orthostatictraining of patients with spinalcord injury. Arch Phys Med Rehabil.1984;65:251-253.12. Dela F, Mohr T, Jensen CMR,et al. Cardiovascular control during exercise:Insights from spinalcord-injured humans. Circulation.2003; 107:2127-33. (24 ref).13. Health Canada. Statistical reporton the health of canadians. . 1999.14. Bauman WA, Spungen AM,Raza. M., et al. Coronary arterydisease: Metabolic riskfactors andlatent disease in individuals withparaplegia. Metabolism. 1992;59:163-163-168.15. Whiteneck GG, Charlifue SW,Frankel HL, et a). Mortality,morbidity, and psychosocialoutcomes of persons spinal cordinjured more than 20 years ago.Paraplegia. 1 992;30:61 7-630.6916. DeVivo MJ, ShewchukRM, Stover SL,et al. A cross-sectionalstudy of the relationshipbetween age and currenthealth status forpersons with spinalcord injuries. Paraplegia.I 992;30:820-827.17. Garshick E, KelleyA, Cohen SA, et al.A prospectiveassessment of mortalityin chronic spinalcord injury. SpinalCord. 2005;43:408-416.18. Phillips WT, KiratliBK, Sarkati M, etal. Effect of spinalcord injury on the heartandcardiovascular fitness.Cuff Probl Cardiol.I 988;23:64 1-720.19. DeVivo MJ, KrauseJS, Lammertse DP.Recent trends in mortalityand causes ofdeath amongpersons with spinalcord injury. Arch PhysMed Rehabil. 1999;80:1411-1419.20. Krum H, HowesLG, Brown DJ,et al. Risk factors forcardiovascular diseasein chronic spinalcord injury patients.Paraplegia. 1992;30:381-388.21. Blair SN, BrodneyS. Effects of physical inactivityand obesity on morbidityand mortality:Current evidenceand research issues.Medicine & Sciencein Sports & Exercise.1999;31 :S646-S662.22. Booth FW,Gordon SE, CarlsonCJ, Hamilton MT. Wagingwar on modernchronic diseases:Primary preventionthrough exercise biology.J App! Physiol. 2000;88:774-787.23. KatzmarzykPT, Gledhill N, ShephardRJ. The economicburden of physicalinactivity incanada.[see comment].CMAJ. 2000; 163:1435-1440.24. LaPorte RE, AdamsLL, Savage DD, BrenesG, Dearwater5, Cook T. The spectrumofphysical activity, cardiovasculardisease and health:An epidemiologicperspective. Am JEpidemiol. 1984;120:507-517.25. Wicks JR, DldridgeNB, CameronBJ, Jones NL. Arm crankingand wheelchair ergometryinelite spinal cord-injuredathletes. Med Sd SportsExerc. 1983;15:224-231.26. Gledhill N, CcxD, Jamnik R. Enduranceathletes’ stroke volumedoes not plateau:Majoradvantage isdiastolic function. Medicine& Science in Sports &Exercise. 1994;26:1116-1121.27. Hicks AL, MartinKA, Ditor DS,et al. Long-term exercisetraining in personswith spinal cordinjury: Effects on strength,arm ergometry performanceand psychologicalwell-being. SpinalCord.2003;41 :34-43.28. Bougenot M,Tordi N, BetikAC, et a). Effects ofa wheelchair ergometertraining programmeonspinal cord-injuredpersons. SpinalCord. 2003;41:451-6.(31 ref).29. Tordi N, DugueB, Klupzinski D,Rasseneur L, RouillonJD, LonsdorferJ. Interval trainingprogram ona wheelchair ergometerfor paraplegic subjects.Spinal Cord. 2001;39:532-7. (30 ref).30. Yim SY, Cho KJ,Park Cl, et al. Effectof wheelchair ergometertraining on spinalcord-injuredparaplegics. YonseiMedical Journal. I 993;34:278-186.7031. Nash, Jacobs PL,Montalvo BM,Klose KJ, Guest RS,NeedhamShropshireBM. Evaluation ofatraining program forpersons with SCIparaplegia using thePARASTEP 1ambulation system:Part5. lower extremityblood flow and hyperemicresponses to occlusionare augmentedby ambulationtraining. Arch PhysMed Rehabil. 1997;78:808-814.32. Nash MS, MontalvoBM, ApplegateB. Lower extremityblood flow andresponses to occlusionischemia differ in exercise-trainedand sedentary tetraplegicpersons. Arch PhysMed Rehabil.1996:77:1260-1265.33. Scremin AM, KurtaL, Gentili A, et al. Increasingmuscle mass in spinalcord injured personswith a functional electricalstimulation exerciseprogram. Arch PhysMed Rehabil.1999;80:1531-1536.34. Hjeltnes N, AksnesA-, Birkeland KI, JohansenJ, Lannem A, Wallberg-Henriksson H.Improved body compositionafter 8 wk of electricallystimulated leg cyclingin tetraplegic patients.American Journalof Physiology - RegulatoryIntegrative & ComparativePhysiology.I 997;273:R1 072-RI079.35. Mohr T, Dela F, HandbergA, BieringSorensenF, Galbo H, KjaerM. Insulin action andlong-term electrically inducedtraining in individualswith spinal cord injuries.Med Sd Sports Exerc.2001:33:1247-1252.36. Thijssen DH, HeesterbeekP, van Kuppevelt DJ,Duysens J, HopmanMT. Local vascularadaptations after hybridtraining in spinalcord-injured subjects.Med Sd Sports Exerc.2005:37:1112-1118.37. Bauman WA,Spungen AM. Metabolicchanges in personsafter spinal cordinjury. Phys MedRehabil Clin NorthAm. 2000;1 1:109-140.38. Clasey JL, Gater DRJr.Body compositionassessment in adultswith spinal cord injury.TopSpinal Cord lnj Rehabil.2007:12:8-19.39. Myers J, LeeM, Kiratli J. Cardiovasculardisease in spinal cordinjury: An overviewofprevalence, risk, evaluation,and management. AmJ Phys Med Rehabil.2007:86:142-1 52.40. Ginis KAM, LatimerAE, Hicks AL, CravenBC. Developmentand evaluation ofan activitymeasure for peoplewith spinal cordinjury. Medicine & Sciencein Sports & Exercise.2005:37:1099-1111.41. Muraki S, EharaY, Yamasaki M. Cardiovascularresponses at the onsetof passive leg cycleexercise in paraplegicswith spinal cord injury.Eur J App! Physiol.2000;81 :271-274.42. Figoni SF, RodgersMM, Glaser RM,et a). Physiologic responsesof paraplegicsandquadriplegics to passiveand active leg cycleergometry. JAmParaplegia Soc. 1990;13:33-39.43. Muraki S, YamasakiM, Ehara Y, KikuchiK, Seki K. Cardiovascularand respiratory responsesto passive leg cycleexercise in peoplewith spinal cordinjuries. EuropeanJournal of AppliedPhysiology & OccupationalPhysiology. I 996;74:23-28.7144. NobregaACL, WilliamsonJW, FriedmanDB, Araujo CGS,Mitchell JH.Cardiovascularresponsesto active andpassive cyclingto movements.Med Sc! SportsExerc. 1994:26:709-714.45. NobunagaAl. Medical grandrounds. orthostatichypotensionin spinal cordinjury. Top SpinalCord In] Rehabil.I 998:4:73-80.46. BaumanWA, Kahn NN,Grimm DR,Spungen AM.Risk factors foratherogenesisandcardiovascularautonomic functionin persons withspinal cordinjury. SpinalCord. 1999;37:601-616.47. FurlanJO, FehlingsMG, ShannonP, NorenbergMD, KrassioukovAV. Descendingvasomotorpathways in humans:Correlationbetween axonalpreservationand cardiovasculardysfunctionafter spinal cordinjury. J Neurotrauma.2003:20:1351-1363.48. MathiasCJ, Frankel HL.Autonomic disturbancesin spinal cordlesions. In: MathiasCJ,Bannister R,eds. AutonomicFailure: A Textbookof Clinical Disordersof the AutonomicNervousSystem. 4thed. Oxford:Oxford UniversityPress; 2002:494-513.49. TeasellRW, Arnold JMO,Krassioukov A,Delaney GA. Cardiovascularconsequencesof loss ofsupraspinal controlof the sympatheticnervous systemafter spinal cordinjury. Arch PhysMedRehabil. 2000:81:506-516.50. SampsonEE, BurnhamRS, AndrewsBJ. Functionalelectrical stimulationeffect on orthostatichypotensionafter spinal cordinjury. Arch PhysMed Rehabil.2000;81:139-143.51. Mallory BS.Autonomicfunction inthe isolated spinalcord. In: DowneyJA, MyersSJ, GonzalesEG, LiebermanJS, eds. ThePhysiologicBasis of RehabilitationMedicine. 2nded. Stoneham(MA): Butterworth-Heinemann;1994:522.52. LehmannKG, Lane JG,Piepmeier JM,Batsford WP.Cardiovascularabnormalitiesaccompanyingacute spinal cordinjury in humans:Incidence,time course andseventy. JAmCoIlCardiol. 1987:10:46-52.53. Chao CY,Cheing GL.The effects oflower-extremityfunctional electricstimulation ontheorthostatic responsesof people withtetraplegia. Archivesof Physical Medicine& Rehabilitation.2005;86:1 427-1433.54. HainsworthR. Syncope andfainting. In: MathiasCJ, BannisterR, eds. AutonomicFailure: ATextbook ofClinical Disorderso the AutonomicNervous System.4th ed. Oxford:Oxford UniversityPress; 2002:761-781.55. HoutmanS, SerradorJM, Colier WNJM,Strijbos DW, ShoemakerK, Hopman MTE.Changesin cerebral oxygenationand blood flowduring LBNP in spinalcord-injuredindividuals.J App!Physiol. 2001;91 :2199-2204.56. Bondar RL,Dunphy PT,Moradshahi P,et al. Cerebrovascularand cardiovascularresponsestograded tilt inpatients withautonomic failure.Stroke. 1997:28:1677-1685.7257. Horowitz DR,Kaufmann H. Autoregulatorycerebral vasodilationoccurs during orthostatichypotension in patientswith primary autonomicfailure. ClinicalAutonomicResearch. 2001;1 1:363-367.58. Hetsel A, ReinhardM, Guschlbauer B, BrauneS. Challenging cerebralautoregulation inpatients with preganglionicautonomic failure. ClinAuton Res. 2003;1 1:363-367.59. Gonzalez F, Chang JY,Banovac K, MessinaD, Martinez-ArizalaA, Kelley RE. Autoregulationof cerebral blood flowin patients with orthostatichypotension after spinalcord injury. Paraplegia.1991 ;29:1-7.60. Houtman S, ColierWNJM, Oeseburg B,Hopman MTE. Systemiccirculation and cerebraloxygenation during head-uptilt in spinal cord injuredindividuals. SpinalCord. 2000;38:158-163.61. Blomqvist CG, StoneHL. Cardiovasculr adjustmentsto gravitational stress.In: Shephard JT,Abboud FM, eds. Handbookof Physiology, the CardiovascularSystem. Vol 3. Maryland:AmericanPhysiological Society;1983:1025-1063.62. Rowell LB. Integrationof cardiovascular controlsystems in dynamicexercise. In: Rowell LB,Shepherd JT, eds. Handbookof Physiology. New York:Oxford UniversityPress; 1996:770-840.63. Raymond J, DavisGM, Clarke J, BryantG. Cardiovascular responsesduring arm exerciseandorthostatic challengein individuals withparaplegia. EurJ AppIPhysiol. 2001 ;85:89-95.64. Warburton DER,Nicol CW, Bredin SSD.Health benefits ofphysical activity: Theevidence.CMAJ. 2006;174:801-809.65. Warburton DER, NicolCW, Bredin SSD. Prescribingexercise as preventivetherapy. CMAJ.2006;174:961 -974.66. Noreau L, ShephardRJ. Return to work afterspinal cord injury: Thepotential contributionofphysical fitness. Paraplegia.I 992;30:563-572.67, WarburtonDER, Eng JJ, KrassioukovA, Sproule S. Cardiovascularhealth and exerciserehabilitation inspinal cord injury. Topicsin Spinal Cord lnjuiyRehabilitation. 2007;13:98-122.68. Jacobs PL, MahoneyET. Peak exercisecapacity of electrically inducedambulation in personswith paraplegia. MedSd Sports Exerc. 2002;34:1551-6.(31 ref).69. Kinzer SM, ConvertinoVA. Role of leg vasculaturein the cardiovascularresponse to arm workin wheel-chair dependentpopulations. ClinPhysiol. 1 989;9:525-525-533.70. Davis GM, ServedioFJ, Glaser RM, GuptaSC, Suryaprasad AG.Cardiovascular responsestoarm cranking and ENS-inducedleg exercise in paraplegics.JApplPhysiol. 1990;69:671-677.71. Sawka MN. Physiologyof upper body exercise.In: Pandolf KB, ed. Exerciseand SportsScience Reviews. Vol14. New York: Macmillan;1986:175-211.7372. Davis GM, ShephardRJ. Sports and recreationfor the physically disabled.In: Strauss RH, ed.Sports Medicine. Phillidelphia:Saunders; 1984:286-304.73. Miles DS, SawkaRM, Glaser RM, WildeSW, Doerr BM, FreyMAB. Assessmentof centralhemodynamics duringarm-crank exercise. ProcIEEE Nat! Aerosp ElectronicsConf. 1982:442-448.74. Freschuss U, KnutssonE. Cardiovascular controlin man with transversespinal cord lesions.Life Sd. 1970;8:421 -424.75. Hjeltnes N. Oxygenuptake and cardiac outputin graded arm exercisein paraplegics with lowlevel spinal lesions.Scand J Rehabil Med.I 977;9: 107-113.76. Hjeltnes N. Controlof medical rehabilitationof para-and tetraplegicsby repeated evaluationofendurance capacity.mt J Sports Med. 1984;5:171-174.77. Hooker SF, FigoniSF, Rodgers MM, et al. Metabolicand hemodynamic responsestoconcurrent voluntaryarm crank and electrical stimulationleg cycle exercise in quadriplegics.JRehabiiRes 0ev. 1992;29:1-11.78. Raymond J, DavisGM, Climstein M, SuttonJR. Cardiorespiratory responsesto arm crankingand electrical stimulationleg cycling in people withparaplegia. MedSd Sports Exerc. 1 999;31:822-8. (31 ref).79. Raymond J, DavisGM, Fahey A, Climstein M,Sutton JR. Oxygen uptakeand heart rateresponses duringarm vs combined arm/electricallystimulated leg exercisein people withparaplegia. Spinal Cord.1 997;35:680-685.80. Mohr T, Dela F, HanbergAl, Biering-SorensenF, Galbo H, Kjaer M. Insulinaction and long-term adaptationto electrically induced cycletraining in severe spinalcord injured individuals.MedSci Sports Exerc. 2001 ;33:1247-1247-1252.81. Figoni SF, RodgersMM, Glaser RM, etal. Physiologic responsesof paraplegics andquadriplegicsto passive and active legcycle ergometry. J AmParaplegia Soc. 1990;13:33-39.82. Figoni SF. Perspectiveson cardiovascular fitnessand SCI. JAm ParaplegiaSoc. 1990;13:63-71.83. Alimi YS, BarthelemyF, Juhan C. Venouspump of the calf: A studyof venous and muscularpressure. J Vasc Surg.I 994;20:728-728-735.84. Hirsch DR, GoldhaberSZ. Medical risk factors.In: Goldhaber SZ ed.Prevention of VenousThromboembo!ism.1993.85. Goodman JM, FreemanMR, Goodman LS.Left ventricular function duringarm exercise:Influence of leg cyclingand lower body positivepressure. J App! Physio!.2007;102:904-912.86. Hopman MTE, MonroeM, Dueck C, PhillipsWT, Skinner JS. Blood redistributionandcirculatory responsesto submaximal arm exercisein persons with spinalcord injury. ScandJRehabi! Med. 1998;30:167-174.7487. Krauss JC, RobergsRA, Depaepe JL, et at. Effectsof electrical stimulation andupper bodytraining after spinal cord injury.Medicine & Sciencein Sports & Exercise.1993;25:1054-1 061.88. Mutton DL, Scremin AM,Barstow TJ, Scott MD,Kunkel OF, CagleTG. Physiologic responsesduring functional electricalstimulation leg cyclingand hybrid exercise in spinalcord injuredsubjects. Arch Phys Med Rehabil.1 997;78:71 2-718.89. Raymond J, Davis GM, ClimsteinM, Sutton JR. Cardiorespiratoryresponses to arm crankingversus arm and electrical stimulation-inducedleg cycling in Sd. Proceedingsof the InternationalMedical Society of Paraplegia.Sydney, Australia: 1995.90. Eng JJ, Miller WC. Rehabilitation:From bedside to communityfollowing spinal cordinjury(SC. In: Eng JJ, TeasellR, Miller WC, et at, eds. SpinalCord Injury RehabilitationEvidence.;2006:1-9.91. American Spinal InjuryAssociation. ReferenceManual for InternationalStandards forNeurological and FunctionalClassification of Spinal CordInjury Patients. Chicago:American SpinalInjury Association; 2002.92. Marino RJ, Ditunno JF,Donovan WH. InternationalStandards for Neurologicaland FunctionalClassification of Spinal CordInjury. Chicago: AmericanSpinal Association; 2000.93. Figoni SF. Spinal corddisabilities: Paraplegia andtetraplegia. In: Durstine JL,Moore GE, eds.Exercise Management forPersons with Chronic Diseasesand Disabilities. 2nded. United States ofAmerica: American Collegeof Sports Medicine; 2003:247-253.94. Ditunno JF, Young WF,Donovan WH, CreasyG. The international standardsbooklet forneurological and functionalclassification of spinalcord injury. Paraplegia.1994;32:70-80.95. American Spinal InjuryAssociation/InternationalMedical Society forParaplegia. Internationalstandards for neurologicaland functional classiflcationofspinal cord injured patients.Chicago:2000.96. Schmid A, Huonker M,Barturen J-, et at. Catecholamines,heart rate, and oxygenuptakeduring exercise in personswith spinal cord injury. JAppI Physiol. 1 998;85:635-641.97. Hopman MTE. Circulatoryresponses during armexercise in individualswith paraplegia. Int JSports Med. 1994;15:126-131.98. Figoni SF. Exerciseresponses and quadriplegia.Med Sci Sports Ex. 1993;23:433-441.99. Koh J, Brown TE, BeightolLA, Ha CY, EckbergDL. Human autonomic rhythms:Vagal cardiacmechanisms in tertaplegicsubjects. J Physiol.1 994;474:483-495.100. Mathias CJ, FrankelHL. The cardiovascularsystem in tetraplegia andparaplegia. In: VinkenPJ, ed. Handbook of ClinicalNeurology. Spinal Cord Trauma.Amsterdam: Elsevier;1992:435-456.101. Steinberg LL, SpositoMMM, Lauro FAA,et al. Plasma level of catecholaminesin paraplegics.Med Sci Sports Ex. 1996;28:143.75102. Lopes P, FigoniS. Current literature onorthostatic hypotension andtraining in SCI patients.Am Correct Thor J. 1982;36:56-59.103. Bush VE, Wight VL, BrownCM, HainsworthR. Vascular responsesto orthostatic stress inpatients with posturaltachycardia syndrome(POTS), in patients with loworthostatic tolerance, andin asymptomatic controls.Clinical Autonomic Research.2000;1 0:279-284.104. Brown CM, HainsworthR. Forearm vascular responsesduring orthostatic stressin controlsubjects and patients withposturally related syncope.ClinicalAutonomic Research.2000;10:57-61.105. Claydon VE, HainsworthR. Salt supplementation improvesorthostatic cerebraland peripheralvascular control in patientswith syncope. Hypertension.2004;43:809-813.106. Hullemann KD, List M,Matthes D, Wiese G,Zika D. Spiroergometricand telemetricinvestigations during the XXIinternational stoke mandevillegames 1972 in heidelberg.Paraplegia.1975;13:109-123.107. Coutts KD, Rhodes EC,McKenzie DC. Submaximalexercise responsesof tetraplegics andparaplegics. J Appl Physiol.1985:59:237-241.108. Coutts KD, Rhodes EC,McKenzie DC. Maximalexercise responses oftetraplegics andparaplegics. Journalof Applied Physiology: Respiratory,Environmental & ExercisePhysiology.1983:55:479-482.109. Elokda AS, NielsenDH, Shields RK. Effect offunctional neuromuscularstimulation onpostural related orthostatic stressin individuals with acutespinal cord injury. JRehabil Res Dev.2000-Oct;37:535-542.110. Lee KA, Hicks G, Nino-MurciaG. Validity and reliabilityof a scale to assess fatigue.Psychiatry Res. 1991:36:291-298.111. Claydon VE, Elliott SL, SheelAW, Krassioukov A. Cardiovascularresponses tovibrostimulation for spermretrieval in men with spinalcord injury. J SpinalCord Med. 2006;29:207-216.112. Farina D. Interpretationof the surface electromyogramin dynamic contractions.Exercise &Sport Sciences Reviews.2006;34:121-127.113. Miaskowski C,Lee KA. Pain, fatigue, and sleepdisturbances in oncologyoutpatientsreceiving radiation therapyfor bone metastasis: Apilot study. J Pain SymptomManage.1999:17:320-332.114. Lee KA, PortilloCJ, Miramontes H. The fatigueexperience for womenwith humanimmunodeficiency virus.J Obstet Gynecol Neonatal Nurs.1999;28:193-200.115. Lee KA, DeJosephJF. Sleep disturbances,vitality, and fatigue amonga select group ofemployed childbearing women.Birth. 1992;19:208-213.76116. Lee KA, Lentz MJ,Taylor DL, Mitchell ES,Woods NE. Fatigueas a response toenvironmental demands in women’slives. Image J Nurs Sch.1994;26:149-154.117. Noble BJ, BorgGAV, Jacobs I. A category-ratioperceived exertion scale:Relationship toblood and muscle lactatesand heart rate. Med SdSports Exerc. 1983;15:523-528.118. Novak V, Novak P,Spies JM, Low PA. Autoregulafionof cerebral blood flowin orthostatichypotension. Stroke. 1998;29:104-111.119. Saltin B, BlomqvistG, Mitchell JH, JohnsonRL,Jr, Wildenthal K, ChapmanCB. Response toexercise after bed rest and aftertraining. Circulation.1968;38:1-78.120. Winker R, BarthA, Bidmon D, et al. Enduranceexercise training in orthostaticintolerance: Arandomized, controlled trial.Hypertension. 2005;45:391-398.121. Earquhar WB, TaylorJA, Darlin SE, Chase KP,Freeman R. Abnormal baroreflexresponses inpatients with idiopathicorthostatic intolerance. Circulation.19;102:3086-3091.122. Convertino VA, Doerr DE,Eckberg DL, EritschJM, Vernikos-Danellis J. Head-downbed restimpairs vagal baroreflex responsesand provokes orthostatichypotension. J App! Physiol.1 990;68: 1458-1464.123. Engelke KA, Doerr DE,Convertino VA. Applicationof acute maximal exercise toprotectorthostatic toleranceafter simulated microgravity.American Journal of Physiology- RegulatoryIntegrative and ComparativePhysiology. 1 996;271:R837-R847.124. Engelke KA, Doerr DF,Convertino VA. A singlebout of exhaustive exerciseaffects integratedbaroreflex function after16 days of head-downtilt. American Journalof Physiology - RegulatoryIntegrative and ComparativePhysiology. 1 995;269:R614-R620.125. Moore AD J, LeeSMC, Charles JB, GreenisenMC, Schneider SM. Maximalexercise asacountermeasure to orthostaticintolerance after spaceflight.Med Sci Sports Exerc.2001 ;33:75-80.126. StegemannJ, Meier U, Skipka W, HartliebW, Hemmer B, TibesU. Effects of a multi-hourimmersion with intermittent exerciseon urinary excretion and tilt tabletolerance in athletes andnonathletes. Aviat Space EnvironMed. I 975;46:26-29.127. Convertino VA, EngelkeKA, Ludwig DA, DoerrDF. Restoration of plasmavolume after 16days of head-down tiltinduced by a single boutof maximal exercise. AmericanJournal ofPhysiology - Regulatory Integrativeand Comparative Physiology.1 996;270:R3-R10.128. Gillen CM, Lee R, MackGW, Tomaselli CM, NishiyasuT, Nadel ER. Plasma volumeexpansion in humansafter a single intenseexercise protocol. J AppI Physiol.1991 ;71 :1914-1920.129. Convertino VA,Adams WC. Enhancedvagal baroreflex responseduring 24 h after acuteexercise. American Journalof Physiology - Regulatory Integrativeand Comparative Physiology.1991 ;260:R570-R575.77130. HalliwilI JR,Taylor JA, HartwigTD, Eckberg DL.Augmented baroreflexheart rate gain aftermoderate-intensity,dynamic exercise.American Journalof Physiology -Regulatory IntegrativeandComparative Physiology.I 996;270:R420-R426.131. Somers VK, ConwayJ, LeWinter M, SleightP. The role of baroreflexsensitivity inpost-exercise hypotension.J Hypertens. I 985;3:S129-SI 30.132. Gillen CM, NishiyasuT, LanghansG, Weseman C,Mack GW, Nadel ER.Cardiovascularandrenal function duringexercise-inducedblood volume expansionin men. J App! Physiol.1 994;76:2602-2610.133. Haskell A, GitlenCM, Mack GW,Nadel ER. Albumininfusion in humansdoes not modelexercise inducedhypervolaemia after24 hours. Acta PhysiolScand. 1998;164:277-284.134. NagashimaK, Wu J, Kavouras SA,Mack GW. Increasedrenal tubular sodiumreabsorptionduring exercise-inducedhypervolemia inhumans. J Appi Physiol.2001 ;91 :1229-1236.135. NagashimaK, Cline GW, MackGW, Shulman GI,Nadel ER. Intenseexercise stimulatesalbumin synthesisin the upright posture.JAppi Physiol. 2000;88:41-46.136. NagashimaK, Mack GW, HaskellA, Nishiyasu T,Nadel ER. Mechanismfor the posture-specific plasmavolume increaseafter a single intenseexercise protocol.J App! Physiol.1 999;86:867-873.137. Yang RC, MackGW, Wolfe RR, NadelER. Albumin synthesisafter intense intermittentexercise in humansubjects. J App!Physiol. 1 998;84:584-592.138. Engelke KA,Shea JD, DoerrDF, Convertino VA.Autonomic functionsand orthostaticresponses 24h after acute intenseexercise in paraplegicsubjects. AmericanJournal of Physiology- Regulatory Integrativeand ComparativePhysiology. 1 994;266:RI189-RI 196.139. Convertino VA.Baroreflex-mediatedheart rate and vascularresistance responses24 h aftermaximal exercise.Med Sci Sports Exerc.2003;35:970-977.140. Slordahl SA,Madslien VOE, StoylenA, Kjos A, HelgerudJ, Wisloff U. Atrioventricularplanedisplacement in untrainedand trained females.Med Sd Sports Exerc.2004;36:1871-1875.141. TakahashiT, Miyamoto Y. Influenceof light physical activityon cardiac responsesduringrecovery from exercisein humans. EurJ App! PhysiolOccup Physiol. 1998;77:305-31 1.142. Wecht JM,De MeersmanRE, Weir JP, BaumanWA, Grimm DR.Effects of autonomicdisruption andinactivity on venousvascular function. AmericanJournal of Physiology- Heart &Circulatory Physiology.2000;278: H51 5-H520.143. Scott JM, EschBT, Lusina SJ,et at. Post-exercisehypotension andcardiovascularresponsesto moderate orthostaticstress in endurance-trainedmales. App! Physlo!Nutr Metab. 2008;33:246-253.78144. Brys M, BrownCM, Marthol H,Franta R, Hilz MJ.Dynamic cerebralautoregulation remainsstable duringphysical challengein healthypersons. AmericanJournal of Physiology- Heart andCirculatoiy Physiology.2003;285:H 1048-HI054.145. Claydon yE,Hainsworth R. Cerebralautoregulation duringorthostatic stressin healthycontrols and inpatients with posturallyrelated syncope.Clinical AutonomicResearch.2003;13:321 -329.146. Kontos HA, WeiEP, Navari RM, LevasseurJE,Rosenblum WI, PattersonJL,Jr. Responses ofcerebral arteriesand arterioles to acutehypotension and hypertension.Am J Physiol.I 978;234:H37I-83.147. Ainslie PN,Pouliri MJ. Ventilatory,cerebrovascular, andcardiovascular interactionsin acutehypoxia: Regulationby carbon dioxide. JApp! Physiol. 2004;97:149-159.148. Nybo L, MailerK, Volianitis S, NielsenB, Secher NH.Effects of hyperthermiaon cerebralblood flow andmetabolism duringprolonged exercisein humans. J App!Physiol. 2002;93:58-64.149. Magyar MT, ValikovicsA, Czuriga I, CsibaL. Changes ofcerebral hemodynamicsinhypertensivesduring physical exercise.Journal of Neuroimaging.2005; 15:64-69.150. Pott F, KnudsenL, Nowak M, NielsenHB, Hanel B, SecherNH. Middlecerebral arterybloodvelocity during rowing.Acta Physiol Scand.1997;160:251-255.151. JorgensenLG, Perko M, HanelB, Schroeder TV, SecherNH. Middle cerebralartery flowvelocity and bloodflow during exerciseand muscle ischemiain humans. J AppIPhysiol.1992;72:l 123-1132.152. Moraine JJ,Lamotte M, BerreJ, Niset G, Leduc A,Naeije R. Relationshipof middle cerebralartery blood flowvelocity to intensityduring dynamic exercisein normal subjects.Eur J AppIPhysiol Occup Physio!.1993:67:35-38.153. Linkis P, JorgensenLG, Olesen HL, MadsenPL, Lassen NA,Secher NH. Dynamicexerciseenhances regionalcerebral arterymean flow velocity.JAppI Physiol.1995;78:12-16.154. Pott F, RayCA, Olesen HL, IdeK, Secher NH. Middlecerebral artery bloodvelocity, arterialdiameter andmuscle sympatheticnerve activity duringpost-exercisemuscle ischaemia.ActaPhysiol Scand.1 997;1 60:43-47.155. Doering TJ,Resch KL, SteuemagelB, Brix J, Schneider B,Fischer GC. Passiveand activeexercises increasecerebral blood flowvelocity in young,healthy individuals.Am J Phys MedRehabil. 1998:77:490-493.156. Pott F, Van LieshoutJJ, Ide K, MadsenP, Secher NH. Middlecerebral arteryblood velocityduring intense staticexercise is dominatedby a vaisalva maneuver.J AppI Physiol. 2003:94:1335-1344.157. ide K, Horn A,Secher NH. Cerebralmetabolic responseto submaximal exercise.JAppIPhysiol. 1999:87:1604-1608.79158. Koch A, IversM, Gehrt A, Schnoor P,Rump A, RieckertH. Cerebral autoregulationistemporarily disturbedin the early recoveryphase after dynamicresistance exercise.ClinicalAutonomic Research.2005;15:83-91.159. Ogoh S, FisherJP, Purkayastha S,et al. Regulationof middle cerebral arteryblood velocityduring recovery from dynamicexercise in humans.JAppi Physiol. 2007;102:713-721.160. Els T, DaffertshoferM, Schroeck H, KuschinskyW, Hennerici M. Comparisonof transcranialdoppler flow velocity andcerebral blood flowduring focal ischemiain rabbits. Ultrasound inMedicine and Biology.1999;25:933-938.161. Hollmann W, StruderHK. Brain, psyche andphysical activity. Orthopade.2000;29:948-956.162. Huber P, Handa J.Effect of contrastmaterial, hypercapnia,hyperventilation, hypertonicglucose and papaverineon the diameter of the cerebralarteries. angiographicdetermination inman. Invest Radio!. 1967;2:17-32.163. Giller CA, BowmanG, Dyer H, et al. Cerebralarterial diametersduring changes in bloodpressure and carbondioxide during craniotomy.Neurosurgery. 1993;32:737-742.164. Low PA, Tuck RR.Effects of changes ofblood pressure, respiratoryacidosis and hypoxiaonblood flow in thesciatic nerve of the rat.Journal of Physiology.VOL. 1984;347:ate ofPubaton:1984.165. Takeuchi M, LowPA. Dynamic peripheralnerve metabolic andvascular responsestoexsanguination. AmericanJournal of Physiology -Endocrinology andMetabolism. 1 987;253:16/4.166. McManis PG, SchmelzerJD, Zollman PJ, Low PA.Blood flow and autoregulationin somaticand autonomic ganglia.comparison with sciaticnerve. Brain. 1997;120:445-449.167. Nelson RJ, CzosnykaM, Pickard JD, et al.Experimental aspects ofcerebrospinalhemodynamics: Therelationship between bloodflow velocity waveformand cerebralautoregulation. Neurosurgery.I 992;31 :705-710.168. Eldar M, BattlerA, Neufeld HN. Transluminalcarbon dioxide-lasercatheter angioplastyfordissolution of atheroscleroticplaques. JAm Coil Cardiol.1984;3:135-137.169. Ogoh S, BrothersM, BarnesQ, et al. The effect of changes incardiac output on middlecerebral arterymean blood velocityat rest and during exercise.J Physiol (Lond).2005;569:697-704.170. Bogert LW,Erol-Yilmaz A, TukkieR, Van Lieshout JJ. Varyingthe heart rate responsetodynamic exercise inpacemaker-dependentsubjects: Effects on cardiacoutput and cerebralbloodvelocity. Clin Sci (Coich).2005;109:493-501.171. Zhang R, ZuckermanJH, Levine BD. Deteriorationof cerebral autoregulationduringorthostatic stress: Insightsfrom the frequencydomain. J App! Physiol.1 998;85: 1113-1122.80172. van Osch MJ,Jansen PA, VingerhoetsRW, van der GrondJ. Association betweensupinecerebral perfusion andsymptomatic orthostatichypotension. Neuroimage.2005;27:789-794.173. Houtman 5, ColierWN, OeseburgB, Hopman MT.Systemic circulationand cerebraloxygenation during head-uptilt in spinal cordinjured individuals. SpinalCord. 2000;38:158-163.174. Prasso JE,Berberian G, CabrerizaSE, et al. Validationof mean arterialpressure as anindicator of acute changesin cardiac output.ASAIO Journal. 2005;51:22-25.175. Hoffman MD. Cardiorespiratoryfitness and trainingin quadriplegics andparaplegics. SportsMed. 1986;3:312-330.176. Shephard RJ, BouhlelE, Vandewalle H, MonadH. Muscle mass as afactor limiting physicalwork. J App! Physiol.I 988;64: 1472-1479.177, Maiorov DN, FehlingsMG, Krassioukov AV.Relationship betweenseverity of spinalcordinjury and abnormalitiesin neurogenic cardiovascularcontrol in consciousrats. J Neurotrauma.1998;15:365-374.178. Wallin BG, StjernbergL. Sympatheticactivity in man after spinalcord injury, outflowto skinbelow the lesion. Brain.1984:107:183-198.179. Thompson.The relationship betweenlean body mass,resting metabolic rate,and peakoxygen consumptionin spinal cord-injuredand able-bodied individuals.[Ph.D.]. Universityof Illinoisat Urbana-Champaign;1998.180. Kjaer M, MohrT, Biering-SorensenF, Bangsbo J. Muscleenzyme adaptationto training andtapering-off in spinal-cord-injuredhumans. Eur J App!Physiol. 2001 ;84:482-486.181. HookerSP, FigoniSF, Rodgers MM, etal.Physiologic effects ofelectrical stimulationlegcycle exercise trainingin spinal cord injuredpersons. Arch PhysMed Rehabil. 1992;73:470-476.182. Barstow TJ,Scremin AME, MuttonDL, Kunkel CF, CagleTG, Whipp BJ. Changesin gasexchange kinetics withtraining in patients withspinal cord injury.Med Sci Sports Exerc.1 996;28:1 221-1228.183. Kjaer M,Dela F, Sorensen FB,et al. Fatty acid kineticsand carbohydratemetabolism duringelectrical exercisein spinal cord-injuredhumans. AmJ Physiol Regul lntegrComp Physiol.2001 ;281 :R1492-8.184. ClausenJP, Klausen K, RasmussenB, Trap-Jensen J.Central and peripheralcirculatorychanges after trainingof the arms or legs.Am J Physiol.1973;225:675-682.185. Ahlborg G, Jensen-UrstadM. Arm blood flow atrest and duringarm exercise. JAppiPhysiol.1991 ;70:928-933.186. RasmussenB, Klausen K, ClausenJP, Trap-Jensen J. Pulmonaryventilation, bloodgases,and blood pH after trainingof the arms or the legs.JAppI Physiol.1975;38:250-256.81187. VolianitisS, Secher NH.Arm blood flowand metabolismduring arm andcombined armandleg exercisein humans.J Physiol (Lond).O1;544:977-984.188. PatersonDH, ShephardRJ, CunninghamD. Effects of physicaltraining on cardiovascularfunction followingmyocardialinfarction. Journalof Applied Physiology:Respiratory, Environmental& Exercise Physiology.1 979;47:482-489.189. Calbet JAL,HolmbergH-, Rosdahl H, VanHall G, Jensen-UrstadM, Saltin B. Whydo armsextract less oxygenthan legs duringexercise? AmericanJournal of Physiology- RegulatoryIntegrative &ComparativePhysiology. 2005;289:R1448-Ri 458.190. Rowell LB.Human circulationregulation duringphysical stress.In: New York:OxfordUniversity Press;1986:213-286.191. DunbarCC, Robertson RJ,Baun R, et al.The validity ofregulating exerciseintensity byratings of perceivedexertion. MedSci Sports Exerc.I 992;24:94-99.192. Chen MJ,Fan X, Moe ST.Criterion-relatedvalidity ofthe borg ratingsof perceived exertionscale in healthyindividuals: Ameta-analysis.J Sports Sci. 2002;20:873-899.193. Wecht JM,Weir JP, DeMeersmanRE, SpungenAM, BaumanWA. Arterial stiffnessinpersons withparaplegia. JSpinal Cord Med.2004;27:255-259.194. De GrootP, Crozier J, RakobowchukM, Hopman M,MacDonald M.Electrical stimulationalters FMDand arterial compliancein extremely inactivelegs. Med SdSports Exerc.2005;37:1 356-1364.195. SyedaB, Gottsauner-WolfM, Denk S, PichlerP, Khorsand A, GlogarD. Arterial compliance:A diagnostic markerfor atheroscleroticplaque burden?.American Journalof Hypertension.2003;16:356-362.196. Tanaka H,Dinenno FA,Monahan KD, ClevengerCM, DeSouza CA,Seals DR. Aging,habitual exercise,and dynamic arterialcompliance. Circulation.2000;102:1270-1275.197. MaedaS, Tanabe T, OtsukiT, SugawaraJ, Ajisaka R, MatsudaM. Acute exerciseincreasessystemic arterialcompliance after6-month exercisetraining in olderwomen. HypertensionResearch. 2008;31:377-381.198. Joyner MJ. Effectof exerciseon arterial compliance...tanaka H, dinennoFA, monahanKD, etal. aging, habitualexercise, and dynamicarterial compliance,circulation. 2000;102:1270-1275.Circulation. 2000;102:1214-1215.199. Rubanyl GM,Romero JC,Vanhoutte PM. Flow-inducedrelease of endothelium-derivedrelaxing factor.American Journalof Physiology- Heart and CirculatoryPhysiology. 1986;250:1 9/6.200. Delp MD, LaughlinMH. Time courseof enhancedendothelium-mediateddilation in aortaoftrained rats. MedSd Sports Exerc.1997;29:1454-1461.82201. Spier SA, LaughlinMH, Delp MD. Effectsof acute and chronicexercise onvasoconstrictorresponsiveness ofrat abdominal aorta.J App! Physiol.1 999;87: 1752-1757.202. Balkestein EJ,van AggelLeijssen DP,van B, StruijkerBoudierHA, Van Bortel LM.The effectof weight loss withor without exercise trainingon large artery compliancein healthy obesemen. JHypertens. 1999;17:1831-1835.203. Yamashita T,Sasahara T, PomeroySE, Collier G,Nestel PJ. Arterialcompliance, bloodpressure, plasmaleptin, and plasmalipids in women areimproved with weightreduction equallywith a meat-baseddiet and a plant-baseddiet. Metabolism:Clinical and Experimental.I 998;47: 1308-1314.204. Toto-MoukouoJJ, AchimastosA, Asmar RG. Pulsewave velocity inpatients with obesityandhypertension. AmHeart J. 1986;112:136-140.205. Goss FL, McDermottA, Robertson RJ.Changes in peakoxygen uptake followingcomputerized functionalelectrical stimulationin the spinal cordinjured. ResQ Exerc Sport.1 992;63:76-79.206. Barstow TJ,Scremin AME, MuttonDL, Kunkel CE,Cagle TG, Whipp BJ.Peak and kineticcardiorespiratoryresponses duringarm and legexercise in patientswith spinal cordinjury. SpinalCord. 2000;38:340-5.(29 ret).207. RaymondJ, Davis GM, BryantG, Clarke J. Cardiovascularresponses toan orthostaticchallenge and electrical-stimulation-inducedleg muscle contractionsin individuals withparaplegia.European Journalof Applied Physiology& Occupational Physiology.1 999;80:205-212.208. Cencetti S, BandinelliG, Lagi A. Effectof PCO2changesinduced by head-uprighttilt ontranscranialdoppler recordings.Stroke. 1997;28:1195-1197.209. Betz E. Cerebralblood flow: Its measurementand regulation. PhysiolRev. I 972;52:595-630.210. lmray CH, WalshS, Clarke T, et al. Effectsof breathing air containing3% carbon dioxide,35% oxygen or amixture of 3% carbondioxide/35% oxygenon cerebral andperipheraloxygenation at 150m and 3459 m. ClinSci (Colch). 2003;104:203-210.211. Lagi A, BacalliS, Cencetti S, PaggettiC, Colzi L. Cerebralautoregulationin orthostatichypotension. A transcranialdoppler study. Stroke.I 994;25: 1771-1775.212. PoulinMJ, Liang P-, RobbinsPA. Dynamics ofthe cerebral blood flowresponse tostepchanges in end-tidal PCO2 andP02 in humans. JApplPhysiol.1996;81:1084-1095.213. Kety SS, SchmidtCF. The effectsof altered arterial tensionsof carbon dioxideand oxygenoncerebral blood flowand cerebral oxygenconsumption ofnormal young men.J Clin Invest. 1948.214. Olesen J, Paulson08, Lassen NA.Regional cerebralblood flow in mandeterminedby theinitial slope of theclearance of intra-arteriallyinjected 133Xe. Stroke.1971 ;2:519-540.83215. EllingsenI, Hauge A, NicolaysenG. Changes inhuman cerebralblood flowdue to stepchanges inP(A02) and P(ACO2).Acta Physic!Scand. 1987;129:157-163.84


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