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Cardiovascular disease risk and central and peripheral responses to exercise in individuals with spinal.. Zbogar, Dominik 2009

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Cardiovascular diseaserisk and central andperipheral responsesto exercise inindividuals with spinalcord injurybyDominik ZbogarA THESIS SUBMITTEDIN PARTIAL FULFILMENTOF THE REQUIREMENTSFORTHE DEGREE OFMASTER OF SCIENCEinTHE FACULTY OFGRADUATE STUDIES(Human Kinetics)THE UNIVERSITYOF BRITISH COLUMBIA(Vancouver)June 2009© Dominik Zbogar,2009AbstractIntroduction: Personswith spinal cord injury (SCI) are oftenphysically inactive and as such are atincreased risk of cardiovascularmorbidity. Fortunately, exercisetraining in SCI can provideimprove health-related physicalfitness and alleviate medicalcomplications associated withdeconditioning. To optimizehealth-related fitness gains of exercisein SCI and maximize thepotential for chronic diseaseprevention it is necessary tounderstand the acute responses(centraland peripheral) to exercise.Purposes: The primarypurposes of this research were to:1) determine the contribution ofcentral/peripheral limitationsto exercise capacity and2) examine vascular health in SCI.Methods: Seven personswith paraplegia and seven able-bodied(AB) individuals participated intwo testing days. Testingday one consisted of incrementalarm crank ergometry to exhaustionwithmeasures of cardiac output,muscle oxygenation, and expiredgas and ventilatory parameters.Testing day two involvedthe measurement of arterial complianceand endothelial function.Results: There was a significantdifference for small artery compliancebetween SCI and AB(6.9±3.7 versus 10.5±1.7m1mmHg-1x100, p< 0.05). Arm totalhaemoglobin increased significantlythroughout exercise. Armoxygenation decreased until 60%of maximal wattage after which valuesdid not change. Thoughnon-significant, the large effect size(eta2=.142) suggests a trend forhigheraerobic power in AB (28.6±5.7mLkg-1min-)than in SCI (23.7±2.77mLkg-1min-)due to a trendfor higher cardiac outputvalues in AB (1 8.0±5.7Lmin-1)thanSCI (15.8±3.4Lmin-1)at maximalexercise.Conclusions: Small arterycompliance is lower in SCI thanAB. Leveling off of deoxygenatedhaemoglobin with total haemoglobinincreasing throughout exercisesuggests a peripherallimitation to arm ergometryin both groups. A trend for highercardiac output in AB suggestsacentral limitation in Sd.IIITable of ContentsABSTRACT.11TABLE OF CONTENTSIIILIST OF TABLESVLIST OF FIGURESVI1. INTRODUCTIONI2. PURPOSES33. OBJECTIVES43.1. CARDIOVASCULAR PARAMETERS43.2. VASCULAR HEALTH43.3. QUALITYOFLIFE44. HYPOTHESES54.1. CARDIOVASCULAR PARAMETERS54.2. VASCULAR HEALTH54.3. QUALITYOF LIFE55. CENTRAL AND PERIPHERAL ADAPTATIONS ANDLIMITATIONS TO EXERCISE 55.1. BACKGROUND55.2. PHYSIOLOGY OF ARM EXERCISE95.3. ACUTE LIMITATIONS IN SCI115.4. CHRONIC EXERCISE RESPONSES IN SCI135.5. MEASUREMENT OF CENTRAL AND PERIPHERALRESPONSES 145.5.1. Central limitations: Acetylene Rebreathing145.5.2. Peripheral limitations: Near Infrared Spectroscopy and ArteriovenousOxygen Difference 146. ENDOTHELIAL FUNCTION176.1. BACKGROUND176.2. MEASURING ENDOTHELIAL FUNCTION186.2.1. Doppler Ultrasonography196.3. PATHOPHYSIOLOGY OF THE ENDOTHELIUM206.4. EXERCISE AND THE ENDOTHELIUM226.5. ENDOTHELIAL DYSFUNCTION IN Sd247. ARTERIAL COMPLIANCE257.1. MEASURING ARTERIAL COMPLIANCE257.2. ARTERIAL COMPLIANCE PHYSIOLOGY267.3. ARTERIAL COMPLIANCE PATHOPHYSIOLOGY277.4. ARTERIAL COMPLIANCE IN EXERCISE287.5. ARTERIAL COMPLIANCE IN SCI298. QUALITY OF LIFE309. RESEARCH METHODS329.1. PARTICIPANTS329.2. TESTING PROCEDURE359.2.1. Exercise Measures35iv9.2.2. Resting Measures.3710. STATISTICAL ANALYSIS4211. RESULTS4211.1. PARTICIPANTS4211.2. EXERCISE MEASURES4311.3. RESTING MEASURES4511.3.1, Arterial Compliance4511.3.2. Endothelial Function4511.4. QUESTIONNAIRES4612. DISCUSSION4712.1. EXERCISE MEASURES4712.1.1. Cardiorespiratory Measures47121.2 Near Infrared Spectroscopy5112.2. RESTING MEASURES5412.3. QUALITY OF LIFE5513. CONCLUSION5714. LIMITATIONS5915. REFERENCES7016. APPENDICES79VList of TablesTable la. Participant characteristics (spinal cord injured) 62Table lb. Participant characteristics (able bodied) 62Table 2. Participant medications 63Table 3. Descriptive Statistics for aerobic power, HR, SV cardiac output, and a-vDO2 during thegraded exercise test 64Table 4. Descriptive statistics for arterial compliance in individuals with SCI and able-bodiedindividuals 65Table 5. Descriptive statistics for endothelial function in individuals with SCI and able-bodiedindividuals 65viList of FiguresFigure 1. Atherosclerosis timeline 66Figure 2a-f. Cardiovascular and aerobic responses to incremental exercise test 67Figure 3a-d. Muscle total haemoglobin and oxygenation response to incremental exercise test test.68Figure 4. Small artery compliance 69Figure 5. Large artery compliance 69I1. IntroductionIn Canadaannual incidence ratesof spinal cord injury (SCI)are estimated to be 35peryear per million population(CPA 2009). In terms ofprevalence, approximately36,000 Canadianslive with spinal cordinjury (SCI) (BCPA 2006),80% of which areexperienced by individuals underage 30 (ICORD 2009).Advances in medicaltreatment over the pastseveral decades haveincreased significantly thelife expectancy of theseindividuals (Hicks et al.2003; Strauss et al.2006; Warburton etal. 2006b). As manyindividuals with SCI nowlive a longer lifespan (Glaser1985; ICORD 2009),they are at risk for developingthe same chronic conditions(such as heartdisease and cancer)as able-bodied persons(DeVivo et al. 1999). Overthe past several decadescardiovascular diseasehas become theleading cause of death inthe SCI population (Le and Price1982; Bauman et al.1992; Bauman et al. 1999a;Myers et al. 2007). The increaseincardiovascular disease(Whiteneck et al. 1992;Bauman et al. 1999a; Bauman etal. 1999b; Jacobsand Nash 2004) as wellas asymptomatic cardiovasculardisease (Bauman et al. 1992;Bauman etal. 1993; Bauman et al.1994; Jacobs and Nash2004) with aging in SCI individualsreflects that ofable bodied individuals,though at an acceleratedrate, higher prevalence, andearlier onset.Given the increased lifeexpectancy of individualswith SCI, considerable SCI researchhasfocused on the managementof health issues associatedwith long-term survival (Ginis et al.2005).A physically inactive lifestyleis associated with prematuremortality and increased riskfor chronicdisease (including heart disease)(LaMonte and Blair 2006;Warburton et al. 2006a; Warburton etaI. 2006b). This is a significantrisk for persons with SCI who, becauseof loss of motor function,are often extremely sedentary(Laporte et al. 1984; Jacobs and Nash2004). As a result, they havelow levels of cardiovascular fitness(Hoffman 1986b), and are at increasedrisk of cardiovascularrelated morbidity and mortality(Jacobs and Nash 2004). Normal wheelchairactivities, i.e. most2activities of dailyliving, are often notadequate to maintaincardiovascular fitnessin persons withSCI (Hoffman 1986b;Figoni 1990; Janssenet al. 1994; Vidal etal. 2003). For instance,approximately onequarter of paraplegicsdo not achieve aerobicpower (V02)levels onarmergometry testssufficient to perform manyactivities of daily living(Noreau et al. 1993). Decreasedcardiovascular fitnessmay result in a cycleof further physicaldecline, ultimately reducing theindividual’s functionalcapacity and theability to live independently,and increasing cardiovasculardisease risk (Warburtonet al. 2006b).In addition to fitnessgains, appropriate exercisetraining in individualswith SCI has thepotential to alleviatemedical complicationsassociated with being veryphysically inactive (e.g.cardiovascular disease,decubitus ulcers, orthostatichypotension) and improverehabilitationoutcome (Glaser 1989).However, while there arevarious exercise programsprescribed toindividuals with Sd, mostare based on studiesof able bodied individuals(Hoffman 1986a).Consequently, the developmentof optimal rehabilitationexercise programs forindividuals with SCIhas yet to occur (Warburtonet al. 2006b). In order tooptimize the aerobic fitnessgains and healthoutcomes of exercisein SCI and to maximize the potentialfor chronic disease prevention, itisnecessary to understandthe acute exercise response(e.g., central and peripherallimitations) ofthese individuals.Individuals with SCI exhibitan increased incidence of hyperlipidaemia,hypertension, typeII diabetes, and hyperinsulinaemia(Bauman et aI. 1992; Bauman etal. 1999a) and diminishedaerobic fitness which areall cardiovascular disease risk factors (Hoffman1 986b; Wecht et al.2000; Wecht et al. 2003). Theendothelium is a layer of cells thatlines every blood vessel in thebody. Due to its location andits numerous functions, endothelial dysfunctionand theaccompanying structural andfunctional changes in the arterial wall areone of the earliest events inthe pathogenesis of cardiovasculardisease and is widely regarded as a necessaryfirst step in the3development of atherosclerosis (Ross1993; Behrendt and Ganz 2002). When damageoccurs tothe endothelium via any of the above-mentionedcardiovascular disease risk factors,its protectiveproperties are compromised which leads to intimal hyperplasiaand a chronic inflammatory statethat creates an atherosclerotic lesion (Rubanyi1993). Inasmuch as this reduced functioninfluences the tone of the arterioles, the increasingblood pressure and decreasing arterialcompliance may be manifestations of the atheroscleroticprocess (Ross 1993; Cohn et al. 2004).Itis therefore important to investigate the vascularhealth of individuals with SCI andthe utility ofearly markers of vascular disease such as measuringarterial compliance and endothelialfunction.2. PurposesThis study examined the cardiac,vascular and peripheral muscle functionof persons withSCI in comparison to the general population.The primary purpose of this investigationwas todetermine the contribution of central(cardiac output) and peripheral(ability to extract and utilizeoxygen) limitations to exercise capacity in individualswith spinal cord injury. The secondarypurpose of this study was to determinethe vascular health of individualswith SCI relative to ablebodied individuals. The tertiary purposeof this study was to examine qualityof life (QOL) inpersons with SCI compared to ablebodied controls. Given the smallernumber of participants andexploratory nature of this studywe have included information oneffect size to assist otherinvestigators to determine appropriateparticipant numbers for parametersbeing measured infuture studies.43. Objectives3.1. CardiovascularparametersTo investigate differencesin central limitationswe investigateddifferences the responseofstroke volume (SV) andcardiac output(Q) between individuals withSCI and able-bodiedcontrols.To investigate differencesperipheral limitationswe investigated responsesin muscle oxygenationand arteriovenous oxygendifference(avDO2) during the arm crankergometry protocolbetweenindividuals with SCIand able-bodied controls.3.2. Vascular HealthFollowing that individualswith SCI are increasedrisk of cardiovasculardisease we wishedto investigate the utilityof two measures whichserve as eay markersof cardiovasculardisease.Thus it was our objectiveto investigate differencesin both endothelialfunction and arterialcompliance betweenindividuals with SCIand able bodied controls.3.3. Quality of lifeQuestionnaires measungQOL can be categorizedas either subjectiveor objectivemeasures. Few studiesinvestigating cardiovascularfunction in SCI haveincluded measuresofQOL (Hicks et al. 2003).Although individualswith SCI are living longer(Glaser 1985; DeVivoet al.1999), theirQOL may remain low. Thereforeit was our objective toinvestigate differencesinsubjective and objectivemeasures ofQOL between groups.54. Hypotheses4.1. Cardiovascular parametersWe hypothesized that individuals with SCI will exhibit alower SV and Q compared to ablebodied controls which would be indicative of central limitation.With respect to peripheral limitationwe anticipated that muscle oxygenation during the arm crankergometry protocol would decreaseto a greater extent in individuals with SCI.4.2. Vascular HealthWe hypothesized that endothelial function would be reduced in SCI individualscomparedto able bodied individuals. Additionally we hypothesized thatarterial compliance, specifically smallartery compliance, would be lower in SCI compared to ablebodied individuals.4.3. Quality of lifeWe anticipated that able-bodied individuals wouldhave a higher QOL, as measured bysubjective and objective questionnaires, than individuals with SCI.5. Central and Peripheral Adaptations andLimitations to Exercise5.1. BackgroundThe transport of oxygen in the body is composed of the interaction of central andperipheral steps summarized by the Fick pnciple:V02 = HR x SV x avDO2where V02 is aerobic power, HR is heart rate, SV is stroke volume, and avDO2 is arteriovenousoxygen difference. Stroke volume is determined by several factors. End diastolic volume influences6stroke volume as strength of ventricular contraction is increased by an enlargement of end diastolicvolume via the Frank-Starling law of the heart; the increase in end diastolic volume results in alengthening of cardiac muscle fibres which improves the force of contraction (Levine 2008).Increased cardiac contractility increases SV through increased force generation independent ofend diastolic volume. The result of increased force generation is a reduction in end systolic volumeand higher SV. Total peripheral resistance affects SV in that arteriolar dilatation with exercisedecreases total peripheral resistance making it easier for the heart to pump blood through enlargedSV (Warburton et al. 2002). The amount that these variables can increase with exercise definesVO2max (Wagner 1991). Traditionally, the cause of the limit to oxygen consumption has beensought in the respiratory system and the heart and its capacity to pump blood (central factors), andin the peripheral circulation and the metabolic capacity of active muscles (peripheral factors)(Gonzalez-Alonso and Calbet 2003). Respiratory limitations are not common in normally activepeople exercising at sea level as the respiratory system is more than capable of moving oxygenfrom the air to the gas-blood interface even during the most severe metabolic demands (Dempseyet al. 1990). It is true that the respiratory system is a limitation in pulmonary gas exchange inpatients with pulmonary disease (Dempsey et al. 1990). Respiratory limitation can also occur inendurance athletes with very high maximal Q. In this situation, hypoxemia, caused by diffusionlimitation which is related to high pulmonary blood flow and short pulmonary mean transit timelimits time for oxygen transfer from alveoli to red blood cells (Dempsey et al. 2008). Theconsequence, expressed in terms of the Fick Principle, is a decrease in arterial oxygen contentwhich reduces VO2max in proportion to the narrowing of avDO2. Individuals with paraplegia havefull innervation to both primary and a number of accessory muscles of inspiration since injury isbelow the cervical level (Sheel et al. 2008) and consequently their respiratory function iscomparable to that in the able bodied population (Haisma et at. 2006). In addition the maximalQ7elicited by arm ergometry is significantly lower than that attainable by leg ergometry (Sawka 1986;Myers et al. 2007). Therefore it is unlikely that respiratory limitations would become a factor in thisinvestigation.The main arguments for Q as a limit to VO2max are: 1) VO2max is achieved when anindividual intensely activates approximately % of total muscle mass. The addition of more activemuscle at VO2max causes no further increase in Q or oxygen uptake; the heart can not provideenough blood flow for all the muscles. 2) The addition of muscles at VO2max results invasoconstriction in the active muscle to maintain arterial pressure (Gonzalez-Alonso and Calbet2003). 3) The capacity of muscles to consume oxygen exceeds that which the heart can deliver(Richardson et al. 1999). Another potential central limitation lies with the pericardium thatsurrounds the heart as, since it limits myocardial distention, it can constrain diastolic filling (Esch etal. 2007). Pericardectomy in foxhounds removed a mechanical constraint on SV and enabled theheart to respond to the high filling pressure at maximal exercise. This resulted in a significantlyhigher SV, Q and VO2max (Stray-Gundersen et al. 1986). This decrease in mechanical constraintallows for an increased left ventricular end diastolic volume and consequently increased SV.Pericardectomy in pigs has yielded the same results (Hammond et al. 1992). ft appears thatchronic aerobic exercise can induce pericardial remodelling since endurance trained athletesexhibit end diastolic pressure-volume curves similar to those observed in animal hearts followingpericardiectomy (Esch et al. 2007). The observation that endurance-trained athletes have anenhanced filling capacity and ability to increase SV to a greater degree than untrained persons(Gledhill et al. 1994; Warburton et al. 2002) supports the contention that endurance-trainedathletes posses an altered pericardium.The avDO2 component of the Fick equation can be divided into Ca02 and Cv02, the arterialand venous content of oxygen, respectively. An increase in avDO2 can be the result of elevated8Ca02 or a decrease in Cv02.Haemoglobin concentration does not change with training and thearterial pressure of oxygen is usually sufficient to maintain arterial saturation of haemoglobin whichmeans that ordinarily Ca02 does not change (Rowell 1986). However, research which increasesCa02 by increasing inspiredoxygen tension (Hopman et al. 2004) or by raising haemoglobinconcentration (Spriet et al. 1986) raises VO2max, which indicates that muscle metabolism is notlimiting.The decrease in CV02 with exercise is a result of increased oxygen extraction by activemuscles. With training this ability of active muscle to extract oxygen is increased. Adjustmentswithin the muscle that may explain the greater extraction is a decrease in the distance for diffusionof 02 between capillaries and cells which is afforded by increased capillarization (Daussin et at.2007). There is evidence to show that a diffusion limitation between the capillaries and themitochondria could occur in normoxia (Roca et al. 1989). However, peak V02 is increased if thisdiffusion limitation is overcome with more oxygen made available to the mitochondria (Richardsonet al. 1999; Saltin and Calbet 2006).A reduction in HR at rest and during standard submaximal workloads, with an inherentreduction in myocardial aerobic requirements, is a significant adaptation to chronic aerobicexercise of a sufficient intensity in able-bodied persons. This response reflects both central andperipheral adaptations (Clausen et al. 1970; Rowell 1986; Daussin et al. 2007). Central adaptationsinvolve improved ability of the heart to deliver blood to working tissues manifested as an enhancedQ with a compensatory decrease in sympathetic stimulation (Frick et al. 1967; Clausen 1977;Mclean and Skinner 1995). The higher blood volume that results from chronic endurance training isa major contributor to enhanced ventricular function (Hopper et aT. 1988). These higher bloodvolumes result in an increased end diastolic volume which increases SV through the Frank-Starlingmechanism (Rowell 1986; Phillips et al. 1998; Warburton et al. 2002). In addition, since trained9individuals have lower blood pressure,ventricular emptying is facilitated by a decrease in afterload,also increasing SV (Gledhill et al. 1994).An improvement in ventricular filling time is responsible forthe finding that in trained athletes SV doesnot plateau as it does in sedentary counterparts(Gledhill et al. 1994; Warburton et al. 2002).Decreased afterload is attributed to adecrease in sympathetic nervous system activity inthe working muscle which is also responsiblefor the increased blood flow, a peripheral adaptation.Other peripheral adaptations, as mentioned,involve increased metabolic capacity in skeletalmuscles resulting from increased capillarizationand mitochondrial density. These peripheralchanges manifest as an increase in avDO2(Clausen 1977; Rowell 1986; Mclean and Skinner 1995;Daussin et al. 2007).Central improvements after training will result fromincreased volume loading by maximallystressing the capacity of the heart and circulation to deliverblood and oxygen to the workingmuscles. Central circulatory adaptations are more likely tooccur when training uses large musclegroups to create high levels of oxygen uptake and Q, asseen in running and cycling (Clausen1977; Reading et al. 1993; Daussin et al. 2007).Peripheral adaptations in skeletal muscle thatoccur after training large muscle groups can also be obtained through exerciseusing smallermuscle groups such as during arm ergometry,although central adaptations are minimized(Clausen 1977). It is believed that central adaptations totraining are more beneficial thanperipheral adaptations in decreasing cardiovascular diseaserisk (Mclean and Skinner 1995).5.2. Physiology of arm exerciseAt any given submaximal power output, HR, systolic and diastolic pressure,minuteventilation, and oxygen uptake are higher during arm exercisecompared to leg exercise, while SV10is lower in arm exercise than in leg exercise (Stenberg et al. 1967; Franklin 1985; Jacobs and Nash2004). Cardiac output remains the same, though it is achieved by differences in HR and SVcontributions (Sawka 1986). Several factors may account for the difference in cardiorespiratoryresponses to the two modes of exercise at equal workloads. Diastolic filling rate and end diastolicvolume is lower in arm exercise than in leg exercise which results in a lower SV (Goodman et al.2007). Mechanical efficiency (workNO2) is lower during arm exercise (Stenberget aL 1967; Phillipset al. 1998). This may result from the use of smaller muscle mass and the static effort of the torsomuscles and hands required of arm work, which increases V02 without increasing workoutput(Franklin 1985; Phillips et al. 1998). The higher rate pressure product(a product of HR and systolicblood pressure) at a given workload for arm exercise compared to leg exerciseis thought to reflectincreased sympathetic tone during arm exercise, potentially mediatedby any combination of:reduced SV with consequent tachycardia, isometric contraction of torso muscles,and sympatheticvasoconstriction in the non-working leg musculature (Franklin 1985; Phillipset al. 1998) whichelicits a greater total peripheral resistance and arterial blood pressureduring arm exercise, whichcan increase afterload, limit left ventricular ejection and decrease SV(Goodman et al. 2007).With maximal exercise, VO2max is lower during arm ergometry, averaging70% comparedto cycling (Sawka 1986; Phillips et al. 1998; Secher and Volianitis 2006).A lower VO2max isattributed to a smaller skeletal muscle mass which results in a decreasedoxidative capacity and areduced ability to create tension (Sawka 1986; Phillips et al. 1998). MaximalQ is also significantlylower (approximately 30%) for arm exercise which correspondsto the lower VO2max (Sawka 1986;Myers et al. 2007).115.3, Acute limitations in SCIFor individuals with SCI who are confined to arm exercise, the ability to generate higherlevels of V02 is further reduced due to metabolic, hormonal, and hemodynamic disturbancesrelated to their injury. Consequently, voluntary exercise capacity in individuals with SCI is lower(Jacobs and Nash 2004) as is the level of aerobic fitness that may be achieved through training(Glaser 1989).Although individuals with paraplegia may show pronounced hypertrophy of the arms due totheir use in ambulation, they are not able to make use of trunk and leg muscles for stabilization andas a fulcrum with which to push during arm exercise (Hopman et al. 2004). They are not able torecruit their muscles as effectively and consequently they attain lower VO2peak values than ablebodied individuals (Hopman et al. 2004).There is also a significant elevation of resting and exercising HR in partial compensationfor a decreased SV in individuals with SCI to maintain Q (Jacobs and Nash 2004). Decreased SVis due to a decreased venous return, resulting in reduced filling pressure and end-diastolic volumes(Jacobs and Nash 2004) caused by impaired blood redistribution during exercise resulting fromabsence of the muscle pump in paralyzed legs and centrally mediated sympathetic control(Hopman et aT. 1992; Hopman et al. 2004).Additionally, aerobic capacity in SCI individuals can be limited by diminished sympatheticoutflow since the normal cardiovascular response involves intact sympathetic reflexes. Normalsympathetic reflexes increase blood flow to metabolically active skeletal muscles to increaseoxygen and fuel substrate provision and metabolite removal (Glaser 1985; Myers et al. 2007). Thisprocess involves vasoconstriction of relatively inactive tissues (e.g. viscera, skin, and nonexercising muscle), venoconstriction, vasodilation of arterioles in exercising muscle, increased HRand contractility and Q. The loss of active muscle and sympathetic contributions in exercise can12result in high fatigabilityof exercising muscle dueto smaller mass, inadequateblood flow, moreanaerobic contributionand increased accumulationof metabolites in muscles(Glaser 1989).Thus, the stimulusof arm exercise may notbe sufficient to increaseSV appreciably(Clausen 1977).Spinal cord injurydisturbs venous return (Jacobsand Nash 2004) andsympathetic reflexes(Glaser 1989). These factorscan lead to reduced stressin the form of volumeloading placed onthe heart during exercise,therefore reducing potentialfor central adaptations.The ability to stresscentral haemodynamicmechanisms is furthercompromised when exercisinginthe traditionalupright seated position(Phillips et al. 1998). Allthese factors, in accordancewith theFrank-Starling mechanism,combine to produce alower SV compared with able-bodiedpersonsunder similar exerciseconditions (Phillips et al. 1998),limiting the potential to improvecardiovascular fitness.However, research has yieldedconflicting results. In astudy by Hopman et al. (1998)investigating maximal exercisein SCI, there was no changein VO2peak despite variousinterventions to increaseSV. These findings suggestthat a peripheral limitation(oxygen utilization)is the limiting factorin VO2peak during arm exercisein SCI individuals. Another studyby the samegroup (Hopman et al. 2004)showed differing resultswith V02 during peak exerciseincreasing withhyperoxia in paraplegicsindicating that VO2peak duringarm exercise is limited byoxygen supplyrather than by small musclemass and related biochemicallimitations. Another study showsthat inparaplegics, central mechanismscan be stressed duringarm ergometry since aftera trainingstimulus there was a significantincrease of 31% in V02related to a SV increase of 16%(Davis etal. 1987). The apparentlyconflicting results of differentstudies maybe explained bythe differentstimuli they apply to investigatecentral versus peripheral limitationsto exercise. It is possible thatthere is no one singlelimitation to VO2max but thatthere are several areasof limitation andtherefore several areasin which aerobic powercan be manipulated.135.4. Chronic exercise responses in SCINumerous reviews have reported that exercise rehabilitationis an effective means ofreducing disease susceptibility in persons with SCI (Glaser1985; Hoffman 1986a; Glaser 1989;Figoni 1990; Jacobs and Nash 2004; Warburton et al. 2006b).Research has shown thatendurance, arm strength, peak power output and VO2peakcan improve through arm training(Figoni 1990). However, the nature of the cardiovascular trainingresponse to arm exercise is notwell understood (Figoni 1990) and studies investigatingthe potential for central adaptations havebeen controversial (Hoffman I 986a). Thusit is unclear whether changes inVO2peak result fromcentral (HR, SV,Q) adaptations or increases in peripheral oxygen extraction(avDO2) or whichchanges are more important (ACSM 2002; Jacobsand Nash 2004). Due to the relatively smallmuscle mass involved in activities suchas wheelchair propulsion or arm ergometry,there ispotentially a decreased abilityto perform aerobic exercise that will create sufficientstimulus formyocardial adaptations (Figoni 1990);thus training is often expected toresult in pepheraIadaptations (Hoffman 1986a). Forexample, a study investigating the effectof functional electricalstimulation leg cycle ergometry (FES-LCE)which may promote greater centralhaemodynamicresponses than arm ergometry concludedthat because of a lack of increase inpost-training V02 orQ with the untrained upper extremities that peripheral adaptations wereresponsible for trainingchanges (Hooker et al. 1992). However,most studies have not directly measuredQ duringexercise in those with SCI (Warburtonet al. 2006b), a consequence of the difficulty inherentinmeasuring Q during maximal exercise (Warburtonet a!. 1999).145.5. Measurement of Central and PeripheralResponses5.5.1. Central limitations: Acetylene RebreathingThe measurement of Q is an important tool in quantifyingthe central limitations andadaptations to exercise. There are numerous methods ofmeasuring Q, both invasive and non-invasive (Warburton et at. 1999). The use of foreign gastechniques, specifically acetylenerebreathing to measure Q has been in use since the 1920s (Grollman1929). Acetylene rebreathinghas become one of the most commonly used non-invasive methods ofmeasuring cardiac output,as it is highly reproducible (Warburton et al. 1998). Theaccuracy of acetylene rebreathing rivals“gold standard” invasive procedures of measuring Q andit has been validated at rest and duringsubmaximal and maximal exercise (Warburton et al. 1999).Rebreathing techniques involve the inhalation of a mixture of soluble (acetylene) andinsoluble (helium) inert gases (Cabrera et al. 1991). The transport of a gas in blood is determinedby its diffusivity and solubility (Warburton et al. 1998). Because acetylene is solubleand does notbind with haemoglobin, it rapidly diffuses across the lung blood-gas barrier and its removal from thelungs is determined by blood flow through the pulmonary capillaries(Warburton et al. 1998;Warburton et aT. 1999). Pulmonary blood flow is taken as Q. Helium, the insoluble gas, is used todetermine the gas volume in the system (Cabrera et al. 1991) and to confirm that adequate mixingof the rebreathing system has occurred (Warburton et al. 1999). Itis important, in the SCIpopulation, to obtain direct measures of Q and aerobic power as submaximalprediction can becomplicated by impairment of sympathetic innervation to the heart (Warburton et al. 2006b).5.5.2. Peripheral limitations: Near Infrared Spectroscopy andArteriovenous Oxygen DifferenceNear infrared spectroscopy (N IRS) is a validated non-invasivetechnique that measuresrelative changes in skeletal muscle oxygenation during exercise(Mancini et al. 1994; Bhambhani15et al. 1998). Near infrared light readily penetrates biological tissue and, with the use of the modifiedBeer-Lambert Law which states that change in light attenuation is proportional to the changes inthe concentrations of tissue chromophores (Kocsis et al. 2006), NIRS allows for detection ofchanges in specific chromophores in humans (Boushel et al. 2001).Three molecules are known to affect near infrared light absorption during changes inoxygen tension, haemoglobin, myoglobin, and cytochrome c oxidase (Boushel and Piantadosi2000). In skeletal muscle, the NIRS signal is mainly derived from the absorption of light byhaemoglobin in small arterioles, capillaries, and venules (Boushel et al. 2001). Since theabsorption spectra of myoglobin and haemoglobin overlap, NIRS does not differentiate betweenthese signals in vivo (Boushel et al. 2001). However, myoglobin occupies approximately 10% of theNIRS light absorption signal (Mancini et al. 1994; Boushel et al. 2001) and cytochrome c oxidasecontributes approximately 2-3% (Boushel et al. 2001), thus the NIRS signal is primarily derivedfrom haemoglobin. At 760nM deoxygenated haemoglobin has a higher light absorbency andoxygenated haemoglogin has a higher absorbency at 850nM (Mancini et al. 1994; McCully andHamaoka 2000). Monitoring concentration changes in these two wavelengths provides an index ofrelative tissue deoxygenation.For every pulse of near infrared light emitted into the tissue there are billions of photons.On average, for every 100 million photons emitted, one will arrive at the detection probe. Theremainder are either absorbed or scattered (Gagnon et al. 2001). The most widely used andversatile NIRS devices are continuous wave spectrometers (Boushel et al. 2001) which usereflected light to study skeletal muscle (McCully and Hamaoka 2000). However, because the pathlength of the light from emitter to detector is unknown (McCully and Hamaoka 2000) and becausethere is no distinction between absorbed or scattered light, quantifying the absolute concentrationof any chromophores in the tissue being illuminated remains challenging (Gagnon et al. 2001).16Instead, continuous NIRS provides trends in the responses of the chromophores to changes inoxygen availability and utilization from a baseline value (Boushel and Piantadosi 2000; Boushel etal. 2001). Using NIRS to measure blood flow requires the use of a light-absorbing tracer (Bousheland Piantadosi 2000). Thus, while total haemoglobin is referred to as a surrogate for blood flow inthis study, without the use of a tracer, changes in this variable can be caused by increased bloodflow, venous obstruction or increased haemoglobin concentration. Increased oxygenatedhaemoglobin can indicate increased arterial inflow, increased oxygen saturation or an increasedconcentration of oxygenated haemoglobin (Raisis 2005). Despite these limitations, NIRS doesprovide important information regarding trends in muscle oxygenation during exercise and recoveryand is a valuable tool in helping to understand the physiology of exercise (Bhambhani et aT. 1998).During exercise in humans, NIRS has been extensively used to measure blood flow in thequadriceps of able-bodied individuals (Bhambhani et al. 1998; Kawaguchi et al. 2006; Kennedy etal. 2006) and during leg exercise in clinical populations such as persons with heart failure (Wilsonet aT. 1989). However, NIRS has been used to a lesser degree during arm ergometry(Jensenurstad et al. 1995). Near infrared spectroscopy has also been used to investigate muscleoxygenation in the paralyzed legs of individuals with SCI during FES cycling (Bhambhani et al.2000) and passive leg movement (Kawashima et al. 2005). However, the measurement of NIRS inarm ergometry in the SCI population has not been investigated.Discussion of avDO2 and its potential role as a limitation during exercise is addressed insection 5.1. The avDO2 depends mainly on the exchange area between the capillary blood and themuscle cells, as well as on the skeletal muscle maximal oxidative capacity (Daussin et al. 2007).Thus it provides information on the peripheral muscle response to exercise. Since we aremeasuring V02 and Q in this study, this peripheral factor will be obtained by manipulation of theFick equation to solve for avDO2: avDO2 V02/Q.176. Endothelial Function6.1. BackgroundThe vascular endothelium is a monolayer of interlinked cells that compose the innermostlayer of blood vessels (Volker 2005). The endothelium works to maintain vascular health through avariety of mechanisms (Ross 1993), sensing changes in its environment and responding to thesestimuli through the production of various biologically active substances that modulate the tone andstructure of the underlying smooth muscle (Rubanyi 1993; Maiorana et al. 2003). The endotheliumserves several vital functions. Endothelial cells tightly interlock to form a selective barrier such thatpassage from the blood into the tissue occurs through the endothelial cell (Ross 1993; Rubanyi1993). The endothelium is involved in capillary transport of water and solutes. It produces andreleases factors that promote or inhibit growth of smooth muscle. A number of antithrombotic,anticoagulant, and fibrinolytic factors are released by the endothelium, providing a non-adhesiveluminal wall (Ross 1993; Behrendt and Ganz 2002; Cohn et al. 2004). The endotheliumparticipates in inflammatory and immune responses, regulates plasma lipids and is involved inangiogenesis and tumour metastasis (Rubanyi 1993). The endothelium is integral to themaintenance of cardiovascular homeostasis, producing and secreting vasoactive substances thatmanipulate vascular tone, and adjusting to the variable haemodynamic and hormonal environment(Rubanyi 1993).It is the regulation of vascular tone that has been the most comprehensively studied aspectof the endothelium (Maiorana et al. 2003). Regulation of vascular tone is accomplished byendothelium-derived vasoactive relaxing and contracting factors (Rubanyi 1993). Relaxing factorsinclude prostacyclin, endothelium-derived hyperpolarizing factor and nitric oxide (NO) (Rubanyi1993). Nitric oxide is generated by the conversion of the amino acid L-arginine to NO and L18citrulline by the enzyme nitric oxide synthase Ill which is constitutively active in the endothelium(Palmer et al. 1988; Volker 2005). Nitric oxide elevates cyclic guanosine monophosphate invascular smooth muscle which causes it to relax. While numerous factors with complex interactionscontribute to the extent of vasomotor control, NO is considered the most important relaxing factor(Moyna and Thompson 2004; Walther et al. 2004). Relaxing factors can be released via numerousstimuli including platelet products, thrombin, hormones, neurotransmitters, changes in oxygentension, and shear stress (Vanhoutte et al. 1986). Constricting factors include endothelin-1,platelet-activating factor, and angiotensin II (Volker 2005). Constricting factors can bereleased byacetyicholine, arachidonic acid, norepinephrine, prostaglandin H2, thrombin, frompharmacologicalagents such as nicotine and high potassium, hypoxia, and pressure and stretch (Volker 2005).6.2. Measuring Endothelial FunctionEndothelial dysfunction is manifested in impaired endothelium-dependentvasodilatationcaused by reduced synthesis/release of NO (Rubanyi 1993). One should note thatNO-relatedvasodilatation is but one of the endothelium related effects of NO and that NO is oneof manymediators produced by the endothelium (Maiorana et al. 2003). Nevertheless, testingofendothelium-dependent vasodilatation is a useful tool for assessing the functional integrityofvascular endothelium in vivo, serving as a surrogate for the bloavailabilityof NO (Behrendt andGanz 2002).Inhibitors of nitric oxide synthase Ill, such as NGmonomethylLarginine(L-NMMA) areinfused to examine ambient NO bioactivity in resting muscle (Green et al. 2004).Endotheliumdependent vasodilators, such as acetylcholine, are used to stimulate NO releasefrom endothelialcells (Maiorana et al. 2003). It is thought that acetylcholine exerts its vasodilatory effectby bindingto the muscarine receptor to activate nitric oxide synthase Ill (Higashi and Yoshizumi2003).19Similarly, endothelium-independent NO vasodilator functionis assessed by infusing sodiumnitroprusside or administering sublingual nitroglycerin whichdonates NO directly to vascularsmooth muscle (Cohn et al. 2004; Green et al. 2004).6.2.1. Doppler UltrasonographyThe infusion of acetylcholine, while the gold standard in themeasurement of endothelialfunction, is invasive. Using high resolution Dopplerultrasonography to measure post-ischaemicflow-mediated dilatation (FMD) of the brachial artery is oneof the most frequently used and wellvalidated non-invasive techniques to assessendothelial function in peripheral arteries (Deanfieldetal. 2005). Flow-mediated dilatation is depressedin those with atherosclerosis and cardiovasculardisease risk factors (Celermajer et al. 1992;Joannides et al. 1995) and correlates well withcoronary vascular endothelial function (Andersonet al. 1995).It is believed that the vasodilatation of reactivehyperaemia that follows a period of limbischaemia comes as a result of increased NO,stimulated by changes in shear stress detectedbyendothelial cells (Kuo et al. 1990; Fathiand Marwick 2001; Green et al. 2004). This processis notfully understood, but likely involvescalcium activated potassium-channel opening,membranehyperpolarization, and calcium-mediated activationof nitric oxide synthase Ill (Deanfieldet al,2005).Depending on the site of occlusion, vasodilatationdung reactive hyperaemia is not solelya result of NO (Doshi et al. 2001) as inhibitionof NO using L-NMMA does not completely inhibittheforearm vascular relaxation caused by reactivehyperaemia induced by upper arm occlusion(Doshiet al. 2001). However, NO does play a major role in limbblood flow response to reactivehyperaemia (Higashi and Yoshizumi 2003) specifically whenocclusion is performed distal to theelbow (Doshi et a!. 2001). Various other factors affect the measurementof flow mediated vascular20reactivity such as food, drugs, exercise and temperature (Corretti et al. 2002). These factors shouldall be addressed or controlled before measurement begins.6.3. Pathophysiology of the endotheliumThe endothelium plays an important role in cardiovascular health and disease owing to itslocation and numerous functions (Rubanyi 1993; Behrendt and Ganz 2002). Endothelialdysfunction has been documented in manifest cardiovascular disease and coronaryatherosclerosis (Sorensen et al. 1997; Walther et al. 2004). It has also been found in the presenceof various coronary risk factors (Celermajer et al. 1994) such as hypertension (Panza et al. 1990),hypercholesterolemia (Chowienczyk et al. 1992), smoking (Celermajeret al. 1993; Adams et al.1997), diabetes, obesity (Walther et al. 2004) and physical inactivity (Thijssen et al. 2008). Thesepathophysiological stimuli provoke vascular injury by upsetting normal regulatory properties of theendothelium via a reduction in the bioavailability of endothelium-derived NO (Rubanyi 1993;Anderson 1999) and by rapid catabolism of available NO by reactive oxygen species toperoxynitrite and hydrogen peroxide that further amplify vascular oxidative stress (Cohn et al.2004). Endothelial dysfunction may involve an imbalance between relaxing and contracting factors,between pro- and anti-thrombotic factors, or between growth-promoting and inhibitory factors(Rubanyi 1993).Endothelial dysfunction is one of the earliest events in the pathogenesis of cardiovasculardisease and is widely regarded as a necessary first step in the development of atherosclerosis(Ross 1993; Rubanyi 1993). Indeed, endothelial function has been shown to be a major prognostictool. For example, Al Suwaidi et al. (2000) measured coronary artery endothelial function in 157patients with coronary artery disease. Only participants showing the lowest tertile of coronaryresponses to acetylcholine experienced cardiovascular events. It has been shown that21atherosclerosis in the peripheral vasculature (brachial artery) is significantly correlated with diseasepresence and severity in the coronary and carotid arteries (Sorensen et al. 1997). Furthermore,studies have also shown that endothelial function in peripheral vasculature shows strongprognostic value in individuals with cardiovascular risk factors (Mancini 2004). Neunteufl et al.(Neunteufl et al. 2000) showed, in five years of follow-up with patients with chest pain whounderwent coronary angiography, that those with impaired brachial artery reactivity were morelikely to undergo surgery than those with normal flow-mediated dilation. To investigate whetherimprovement in endothelial dysfunction predicts improved long-term outlook Modena et al. (2002)studied 400 postmenopausal women with hypertension. Brachial artery FMD was measured beforeand six months following normalization of blood pressure (Modena et al. 2002). Event rates wereseven times higher in women who improved FMD by <10% compared to those who improved FMDby>10%. These studies show that preservation of endothelial function and reversal of dysfunctionis an important therapeutic goal.Most cardiovascular disease events result from atherosclerosis (Grey et al. 2003), adisease process originating in the walls of arteries manifested at an early stage in lesions known as“fatty streaks”, and later as advanced fibrous plaques that may impede blood flow and cause acutecardiac events (Ross 1993). In the intact endothelium, many of the protective functions aremediated by NO (Behrendt and Ganz 2002). Conversely, the dysfunctional endothelium that hasreduced synthesis/release of NO, promotes the process of atherosclerosis (Rubanyi 1993; Alam etal. 2005) and thus has a significant effect on the long-term risk for cardiovascular disease (Leesonetal. 1997).Atherosclerosis results from chronic minor endothelial damage that induces intimalhyperplasia and a chronic inflammatory state creating an atherosclerotic lesion (Munro and Cotran1988). Nitric oxide is a free radical scavenger, and its reduced synthesis/release leads to the22existence of more superoxide anion radicals with greater ability to oxidize low-density lipoproteins(LDL) creating oxidized LDL (Rubanyi 1993). Oxidized LDL is a key component in endothelial injury(Ross 1993). Once formed, oxidized LDL may directly injure the endothelium and play a role in theincreased adherence and migration of monocytes into the intima. Here monocytes may beconverted to macrophages by oxidized LDL and other atherogenic substances (Ross 1993). Themacrophages then incorporate oxidized LDL and turn into foam cells (Munro and Cotran 1988;Ross 1993). Platelets, endothelial cells, and macrophages release growth factors which promotesmooth muscle cell proliferation and migration (Munro and Cotran 1988). Macrophages andproliferating smooth-muscle cells synthesize extracellular matx proteins that, over a peod ofdecades, lead to the development of an atherosclerotic plaque (see figure 1) (Munro and Cotran1988). By losing its protective properties and allowing the unopposed action of atherogenic factorson the vessel wall, endothelial dysfunction is a major promoter of atherogenesis and thrombosisand consequently, cardiovascular events (Behrendt and Ganz 2002).6.4. Exercise and the endotheliumVarious pharmacological interventions such as ACE inhibitors, L-arginine supplementation,and smoking cessation have been shown to improve endothelial function in a variety ofcardiovascular disease states (Moyna and Thompson 2004). Regular exercise represents a nonpharmacological option to maintain or improve endotheliaT dysfunction (Moyna and Thompson2004). The repetitive augmentation of blood flow and shear stress brought about by regularexercise positively affects vascular reactivity. This improvement occurs in the form of up-regulationof NO bioactivity through increased protein expression of eNOS and enhanced phosphorylation ofeNOS, resulting in overall enhanced vasodilation and attenuated vasoconstriction to vasoactivefactors (Maiorana et al. 2003; Walther et al. 2004; Volker 2005). In addition to increasing eNOS23expression and phosphorylation exercise training positively affects NO half life by reducing NOdegradation by reactive oxygen species (Walther et al. 2004).Animal studies suggest that short-term exercise training enhances eNOS and NOproduction and bioactivity, producing a short-term buffer to the increased shear stress of exercise(Green et al. 2004). Following prolonged training, the increased production of NO and possiblyother mediators induces structural changes in the vessels resulting in an increase in lumendiameter (Prior et al. 2003). This adaptation normalizes shear stress and endothelial NO activityreturns towards initial levels (Green et al. 2004). In animal models of pathological states includinghypercholesterolemia (Niebauer et aI. 1999), hypertension (Yen et al. 1995), diabetes (Sakamotoet al. 1998), and heart failure (Lindsay et al. 1992; Wang et al. 1997) there is evidence thatexercise training can improve NO-related endothelial function.In humans, cross-sectional exercise studies have found both enhancement (Kingwell et al.1996) and no difference (Taddei et al. 2000) in endothelial function between active and sedentaryyoung men. Similarly, longitudinal studies have shown that exercise training does (Clarkson et al.1999) and does not (Kingwell et al. 1997b) significantly impact endothelial function when assessedin healthy young men. However, exercise studies using clinical populations (i.e. those withendothelial dysfunction) including individuals with heart failure (Hambrecht et al. 2000a), CAD(Hambrecht et al. 2000c), or in the elderly (Taddei et al. 2000), all show that physical activity clearlyhas a beneficial effect on endothelial function. This evidence suggests that a greater training loadmay be needed to improve endothelial function in healthy, young individuals (Clarkson et aT. 1999)than in conditions associated with endothelial dysfunction or to combat the negative effects ofageing (Green et al. 2004). Also, it appears that individuals with endothelial dysfunction respondmore rapidly to training than healthy individuals, with endothelial function improving after as little asfour weeks (Hambrecht et al. 2000b; Linke et al. 2001).24In terms of whether endothelial adaptations are local or systemic in nature, recent studieshave shown that the vascular shear stress that accompanies whole body exercise training canenhance endothelial NO-related vasodilator capacity not only in the active muscle bed but alsosystemically (Green et al. 2002; Maiorana et al. 2003). Exercise training involving a large musclemass causes HR and pulse pressure to increase, resulting in systemic increases in pulsatile flowand pulse pressure (Maiorana et al. 2003). Endurance exercise using the legs is shown to augmentNO-mediated dilation in the untrained forearm (Kingwell et al. 1996). Additionally, these effects onthe endothelium appear to extend to the coronary circulation (Hambrecht et al. 2000c).6.5. Endothelial dysfunction in SCIResearch regarding endothelial function in SCI is lacking. A number of risk factors forcardiovascular disease and endothelial dysfunction have been demonstrated in individuals withSCI (Bauman et al. 1999a). These include hyperlipidaemia, hypertension, type II diabetes, andhyperinsulinaemia (Bauman et al. 1992; Bauman et al. 1999a) as well as diminished physicalactivity and/or aerobic fitness (Hoffman 1986b; Wecht et al. 2000; Wecht et al. 2003). Additionally,the volume and velocity of lower extremity circulation is much lower after SCI (Jacobs and Nash2004). This circulatory hypokinesis (Hjeltnes and Vokac 1979) is a result of loss of autonomiccontrol of blood flow and a decreased regulation of local blood flow by the endothelium (Nash etal.1996; Jacobs and Nash 2004). Low venous compliance (Miranda and Hassouna 2000) as well asdecreased volume and velocity are associated with an increased risk for venous thrombosis(Green et al. 1992; Jacobs and Nash 2004). It also appears that there are pathologicalhaematological factors, such as abnormal platelet function (aggregability and release ofatherogenic mitogens) in which the endothelium plays a main role, directly involved inatherosclerosis in the SCI population (Bauman et al. 1999b).257. Arterial ComplianceWhen the aortic valve closes after ejection of SV, the decay of blood pressure prior to thenext heart beat describes a waveform that depends on the compliance of the arterial system intowhich the blood is being delivered (Cohn 1998). The ratio of change in volume to change inpressure defines arterial compliance (Syeda et al. 2003). It signifies the ability of a vessel to storeblood volume temporarily as it is ejected with each cardiac contraction (Cohn 1998; Glasser 2000).Higher values indicate a less stiff/more compliant vasculature.7.1. Measuring arterial complianceMeasures of arterial compliance can be assessed with applanation tonometry, used tonon-invasively obtain the arterial pressure waveforms for pulse wave analysis (Cohn et al. 1995;Hayward et al. 2002; Matthys and Verdonck 2002; Syeda et al. 2003). The arterial pressurewaveform is created by the overlapping of two waves, a forward pressure wave of ventricularcontraction and a reflected wave from the vascular periphery (McVeigh et al. 1999; Mackenzie etal. 2002). Applanation tonometry involves placing a tonometer over a superficial artery to minimallyflatten (applanate) the arterial wall (Matthys and Verdonck 2002). In normalizing the circumferentialstresses, the electrical resistance of a small piezoelectric crystal within the tip of the tonometervaries directly with intra-arterial pressure (Hayward et al. 2002). This allows for recording of thepressure waveform. Analysis of the pulse wave is accomplished through use of a modifiedWindkessel model of circulation, a well established electrical analog model that treats the arterialvasculature as a hydraulic filter converting pulsatile flow from the heart to steady flow in thecapillaries during diastole (Cohn et al. 1995; Cohn 1998; McVeigh et al. 1999).267.2. Arterial compliance physiologyThe arterial system is composed of large elastic arteries and smaller muscular peripheralarteries. The wall of arteries consists of the adventitia, media, and intima, with a single layer ofendothelial cells (see section 6) separating blood from the vessel (Volker 2005). Large arterieshave much elastin and collagen and smaller arteries are rich in smooth muscle. Elastin fibres playan important part in determining vessel behaviour at lower pressures and collagen fibres play alarger role at higher pressures (Bank et al. 1996).Large elastic arteries such as the aorta buffer the flow and pressure vaation created bythe left ventricle as it contracts and, as the Windkessel model descbes, converts pulsatile flow tosteady flow at the peripheries (McVeigh et al. 1999). This maintains continuous tissue oxygenationand decreases cardiac work. Elastic recoil of the central arteries in diastole is important forcoronary perfusion and a loss of this elasticity impairs coronary flow and may contribute tocoronary artery disease (Jani and Rajkumar 2006).The determinants of change in compliance also differ between large, small, and resistancearteries. In large arteries, collagen and elastin are the determinants of function (Cohnet al. 2004).In smaller arteries (such as the radial artery) vascular smooth muscle function, mediatedby theendothelium, plays a role in determining compliance and calibre. In resistancearteries, NOreleased from the endothelium penetrates the thin-walled arteries and is essentialin determiningcalibre and compliance via its actions on smooth muscle (Vaughn et al. 1998; Cohn etal. 2004).The velocity at which the pressure waveform travels through the vasculature is positivelycorrelated with the stiffness of the vessel walls (Mackenzie et al. 2002). In elastic vessels, thereflected wave tends to arrive back at the aortic root during diastole; this increases diastolicpressure and therefore improves coronary artery perfusion (Mackenzie et al. 2002). In stiff arteries,the reflected wave travels faster and arrives back at the aortic root during systole. This causes an27increased systolic and decreased diastolic pressure (Mackenzie et al. 2002; Syeda et al. 2003).High central systolic pressures increase the workload of the heart, promoting ventricularhypertrophy, and low diastolic pressures reduce coronary artery perfusion (van Popele et al. 2001;Mackenzie et al. 2002).Stiffening occurring in different parts of the vasculature (large conduit arteries, smallarteries, and arterioles) will have a different effect on the appearance of the pressure waveform.Stiffening of the aorta and large conduit arteries accelerates pulse wave velocity and increasespulse pressure via increased systolic and decreased diastolic pressure (Beltran et al. 2001).Stiffening of small arteries will alter the timing and decay rate of reflections that change the contourof the pressure wave. Stiffening of arterioles results in an increase in mean arterial pressure (Cohnet al. 2004).7.3. Arterial compliance pathophysiologyEndothelial dysfunction and the accompanying structural and functionalchanges in thearterial wall are the earliest markers of atherosclerosis and coronary artery disease(Hayoz et al.1992; Cohn 1998). Inasmuch as this reduced function influences the tone of the arterioles,theincreasing blood pressure and decreasing arterial compliance may be manifestationsof theatherosclerotic process (Ross 1993; Cohn et al. 2004). Endothelial dysfunction occursin the entirearterial system but is most easily identified in very small arteries and arterioles (Vaughn et al. 1998;Hypertension Diagnostics 2002). Changes in small artery elasticity may be due to structural orfunctional changes closely tied to endothelial dysfunction (Grey et al. 2003).In recent years, researchers have used pulse wave analysis to show that arterial stiffnessis associated with atherosclerosis (van Popele et al. 2001) and atherosclerotic burden, that is,compliance decreases as the amount and severity of atherosclerosis increases (Syeda et al.282003). Importantly, changes in the compliance of small and large arteries do precede (by years)the presence of plaques characteristic of atherosclerosis (Grey et al. 2003). These changes areimportant early predictors of the risk of cardiovascular disease events (Grey et al. 2003; Cohn et al.2004).Factors such as hypertension (Cohn et al. 1995; Grey et al. 2003), coronary artery disease(Grey et al. 2003), and diabetes (Grey et al. 2003), in addition to being endothelial dysfunction riskfactors, are associated with a decrease in small artery compliance. Preliminary analyses alsosupport the use of the modified Windkessel model in identifying individuals at risk foratherosclerotic events such as heart attack and stroke (Grey et al. 2003). Large arterycompliancehas also been shown to have a strong association with cardiovascular risk factors such ashypertension (Arnett et al. 2001; Waring et al. 2004). In many of the above mentionedrisk factors,a dose response pattern has been observed, with the intensity of exposure to risk factors beingpredictive of vascular dysfunction (Waring et al. 2004). The evaluation of arterialcompliance thusplays an important role in helping to identify those who are at increased risk for cardiovasculardisease.7.4. Arterial compliance in exerciseCross-sectional studies have shown that endurance trained individuals have greaterarterial compliance than matched controls (Cameron and Dart 1994; Kingwell et al.1997a).Endurance-trained individuals also show an absent or attenuated decrease in arterial compliancewith age (Tanaka et al. 1998; Tanaka et al. 2000).Aerobic exercise has proven to be effective in increasing arterial compliance (Cameronand Dart 1994; Tanaka et al. 2000; Parnell et al. 2002). Exercise training studies have shown thatthe arterial compliance of otherwise-healthy sedentary individuals improves within a brief period of29aerobic exercise training (Tanaka et al. 2000) and even following an acute bout of moderateexercise (Cameron and Dart 1994). In the clinical setting, increases in arterial compliance (35%) inindividuals with congestive heart failure have been documented following an eight week exerciseprogram (Pamell et al. 2002).There are several mechanisms through which improvements in arterial compliance arethought to occur. Since biochemical changes in the actual composition of the arterial wall arebelieved to occur over a period of years (Tanaka et al. 2000), changes in arterial compliance seenin short-term aerobic exercise studies must occur through other means. Onepossibility is that theincreased pulse pressure and mechanical distention during exercise sessionsstretch collagenfibres and modify their cross-linking, resulting in increased arterial compliance(Bruel et al. 1998;Tanaka et al. 2000). Arterial compliance can also be altered via modulationof sympatheticadrenergic tone of smooth muscle cells in the arterial wall (Boutouyrieet al. 1994). Thus, it ispossible that regular exercise improves arterial compliance by reducing thechronic suppressiveinfluence of the sympathetic-adrenergic tone either directly or by improving the sympathoinhibitoryeffect of NO.7.5. Arterial compliance in SCIIndividuals with SCI show an increased prevalence for a number ofcardiovascular riskfactors (ACSM 2002; Wecht et al. 2004) associated with decreased arterialcompliance (Wecht etal. 2004). A recent finding suggests that normotensive individuals with paraplegiaexhibitdecreased arterial compliance compared to able-bodied controls (Wecht et a?. 2004). Thesefindings were confirmed in a recent study by our research group in females with SC? (Zbogar et a?.2008). Functional electrical stimulation leg cycle ergometry exercise has been shown to have abeneficial effect on small artery compliance in persons with SC? (Zbogar et a?.2008). Further30research is warranted, since the detection of early vascular disease is essential for preventing,determining, and treating cardiovascular disease.8. Quality of LifeThere is consistent evidence that regular exercise improves fitness in individuals with SCI(Glaser 1985; Hoffman 1986a; Figoni 1990; Davis et al. 1991; Anderson 2004; Jacobs and Nash2004). The importance of physical activity in SCI rehabilitation is continually gaining morerecognition for its ability to promote functional independence (Hicks et al. 2003; Ginis and Hicks2005) and decrease the risk of chronic disease (Noreau and Shephard 1995). Indeed, the vastmajority of individuals with SCI believe that exercise is an essential part of rehabilitation (Anderson2004). However, people with SCI remain among the most inactive segment of society (Ginis andHicks 2005). Few individuals with SCI have the requisite fitness required to carry out activities ofdaily living and this negatively affects quality of life (QOL) (Noreau and Shephard 1995; Ginis andHicks 2005). Quality of life has been defined by the World Health Organization as:“individuals’ perceptions of their position in life in the context of the cultureand value systems in which they live and in relation to their goals,expectations, standards and concerns.” (1998)Health-related quality of life (HRQOL) is an individual’s satisfaction or happiness withdomains of life insofar as they affect or are affected by health. HRQOL can be distinguished fromquality of life as defined above in that it concerns itself primarily with those factors that fall underthe purview of health care providers and health care systems (Wilson and Cleary 1995).Generally speaking, then, assessment of HRQOL represents an attempt to determine howvariables within the dimension of health (e.g., a disease or its treatment) relate to particular31dimensions of life that have been determined to be important to people in general (genericHRQOL) or to people who have a specific disease (condition-specific HRQOL). Mostconceptualizations of HRQOL emphasize the effects of disease on physical, social/role,psychological/emotional, and cognitive functioning. Symptoms, health perceptions, and overallquality of life are often included in the concept domain of HRQOL (Ware 1995).Most HRQOL instruments are considered objective approaches to QOL measurement. Inthe objective approach QOL is measured as a one’s score on an index composed indicators of “thegood things in life”. The index is composed of underlying values that are generally those of societyor the investigators only and are not made explicit. The index assumes that (1) the same domainsof life are important to all people; (2) in each area, all people have the same needs and goals; and(3) happiness and satisfaction are directly proportional to the degree that these standard needs aresatisfied and the goals met.In contrast to the objective approach is the view that the quality of one’s life can only bedetermined by the person living it. This subjective approach focuses on the individual’s subjectiveview of QOL. Here QOL is defined as the reaction, either more cognitive or evaluative (lifesatisfaction) or affective (happiness, morale), to the congruence or discrepancy between aperson’s standards, goals, values, and his/her actual situation and accomplishments. This studyincluded questionnaires from both approaches; some objective and others subjective in nature.While many studies have investigated cardiovascular function in SCI , few have includedmeasures of QOL (Hicks et aT. 2003) despite the fact that research consistently shows that chronicexercise has beneficial effects on numerous subjective outcomes such as depression, selfconcept, and QOL (Noreau and Shephard 1995; Hicks et al. 2003). This is an important issue toaddress. Although individuals with SCI are living longer (Glaser 1985; DeVivo et al. 1999), theirQOL may remain low.32Studies comparing QOL inindividuals with SCI compared toable-bodied individuals showthat the average scoresof SCI groups are significantlylower although the differences arenot aslarge as might be expected(Dijkers 2005). Studies employingthe Medical Outcomes Study 36-item Short Form (SF-36)(see Methods 8.22.3) expectedlyshow lower scores on PhysicalFunctioning and Role LimitationsDue to Physical Problems inthe SCI population compared toable-bodied persons (Leducand Lepage 2002; Post andNoreau 2005). Using other measuresofQOL assessment, scoresof mental health, vitality, androle limitations due to emotional problemsand the mental dimensionscore are not lower in SCI than in thegeneral population (Leduc andLepage 2002; Post and Noreau2005). Nevertheless, in general moststudies show significantlylower QOL scores across domainsin persons with SCI compared to thegeneral populationalthough these differencesare not as large as expected (Post andNoreau 2005). Further researchis warranted, since QOL isaffected by Sd.9. Research Methods9.1. ParticipantsEight asymptomatic paraplegics with SCIlesions of traumatic origin were recruited. Eightage-, gender-, and activity-matchedable-bodied controls were recruited. Activity matchingwasfacilitated via a physical activity assessmentquestionnaire which asks participants aboutphysicalactivity frequency, intensity, duration, andmode (see Appendix B). Participant characteristicsarepresented in Table la-b. All participants werebetween the ages of 18-46 and were asymptomatic,non-smokers, not currently using medicationsthat would affect their autonomic, cardiovascular,respiratory, or metabolic responsiveness toexercise. We attempted to restrict the participantpopulation to individuals with a lesion betweenthe sixth and twelfth thoracic neurological level (T6-33T12) and with at least one year elapsed since time of injury. Above the T6 level, lesions may affectsympathetic stimulation to the heart; including these individuals would causea large variation inexercise response. Participants with SCI were assessed via the American Spinal Injury Association(ASIA) classification of spinal cord injury (see Appendix E). We attempted to recruit individualswithgrade A or B on the ASIA impairment scale. Improvement or recovery from SCI largely occurs inthe first 6 months after injury and is complete by 2 years (McDonald et al. 2002).The literatureshows that those individuals with an ASIA Grade A SCI do not recover by morethan one grade 2years after injury. In individuals with incomplete SCI small improvements mayoccur after 2 years(McDonald et al. 2002). Thus, if study participants had been recently assessed(within 1 year) withthe ASIA classification that grading was used. These selection criteria wereapplied to decreasethe variable exercise responses of including participants having differentaetiologies, types andlevels of spinal injury (Lassau-Wray and Ward 2000; Jacobsand Nash 2004).Autonomic dysreflexia is a serious condition occurring in those withan SCI lesion at orabove T6. Autonomic dysreflexia is rarely seen in individuals with lesions belowT6 and when itoccurs the reaction is often milder (Blackmer 2003). It results from noxious stimulito intact sensorynerves below the level of injury which leads to relatively unopposed sympatheticoutflow and acutehypertension. Parasympathetic outflow from the vagus nervecauses reflexive bradycardia, but thisis insufficient to offset the widespread vasoconstriction (Blackmer 2003).Individuals with SCI wereasked if they experience autonomic dysreflexia. These individuals were excludedfrom the study asexercise is a known cause for autonomic dysreflexia (Jacobs and Nash2004). All participants wereinstructed to perform their bowel and bladder emptying routines priorto all tests. Bladder andbowel distention are the first and second most common causes of autonomicdysreflexia,respectively. Blood pressure was monitored at the conclusion of every exercisestage. Additional34exclusion criteria included ischaemic heart disease, unstable angina, dysrhythmia, recentosteoporotic fracture and tracheostomy (Hicks et al. 2003).Common medications used by individuals with SCI in the non-acute period of injury dealwith pain and spasticity as well as bowel and bladder dysfunction. Pharmacological agentsused totreat neuropathic pain include anti-epileptic drugs such as Gabapentin (Neurontin) andCarbamazepine (Tegretol) and tricyclic antidepressants such as amitriptyline (Elavil), doxepin(Sinequan), and mortriptyline (Pamelor). For the treatment of musculoskeletal pain musclerelaxants and nonsteroidal anti-inflammatory drugs are used. Medications used to treat spasticityinclude GABAb agonists (Baclofen), GABAa agonists such as diazepam (Valium),alpha 2-adrenergic agonists such as clonidine (Catapress) and tizanidine (Zanaflex), datrolene sodium(Dantrium), nerve blocks with injections of phenol or absolute alcohol,and botulinum toxin.Medications dealing with bowel management include stool softeners suchas docusate sodium(Colace), bulkforming agents, stimulants (Senna), and contact irritantssuch as bisacodyl (Dulcolax,Magic Bullet, Therevac, Fleets) and glycerin suppositories. Many of these canbe started initiallyafter the injury and gradually be discontinued. Others may be used occasionally whenproblemsdevelop. Bladder medications fall in the classes of anticholinergics (oxybytynin, tolteridine,andpropanthelene) and alpha adrenergic blockers (tamsulosin, terazosin, doxazosin,prazosin) (Sceizaand Shatzer 2003). Medications being taken by participants and their potentialcardiovascular sideeffects were recorded (see Table 2).Control participants were recruited via advertisements on the Universityof British Columbiacampus. Individuals with SC? were recruited primarily through the G.F. StrongRehabilitation CentreSpinal Cord Program.359.2. Testing ProcedureEach group participated in twotesting days at the Cardiovascular Physiology andResearch Laboratory at the Universityof British Columbia. On the exercise testingday eachparticipant signed an informedconsent form outlining the experimental proceduresand a PAR-Qform. Measurements obtained onthe exercise testing day consisted of the assessmentof oxygenconsumption, cardiac output, andperipheral muscle function during incrementalexercise. Thevascular assessment day consisted of the assessmentof endothelial function, arterial compliance,the participants’ health status, and QOL.9.2.1. Exercise Measures9.2.1 .1. Arm Crank Ergometry ProtocolParticipants were seated at the electronicallybraked arm ergometer (Ergometricser800SH, Ergoline, Germany). The participantand ergometer were positioned such that theaxis ofthe crank arm was set to shoulder height andthe elbows slightly flexed at the point of furthestreach. Data collection began with 8mm of baseline measurements of blood pressure, oxygenconsumption (via mass spectroscopy), cardiacfunction (via ECG and acetylene rebreathing), andperipheral muscle oxygenation and utilization (NIRSand acetylene rebreathing). lndMduals withSCI had their height measured in the supineposition resting on a plinth. Able bodied individualshad their standing height measured. Body weightwas obtained using a scale capable ofaccommodating a wheelchair (Seca 684, CA, USA).Following the 10 minutes of baseline measures,arm crank ergometry commenced. Thisexercise test consisted of 3-minute stages of exercise beginningat a power output of 10-15 wattsand increasing 10-15 Watts per stage until theparticipant reached volitional fatigue. Each 3 minutestage was concluded with a 60 second recoveryperiod, the purpose being to provide a time36interval in which to collect haemodynamicmeasurements without motion artefact (Franklin 1985).This protocol is valid as studies examining thephysiological responses to continuous versusintermittent arm exercise protocols show that significantdifferences do not exist between theVO2max attained viathese protocols (Sawka 1986). While changes in central haemodynamicsoccur immediately upon cessationof arm exercise (Miles et al. 1984), in this study all measureswere obtained during exercise except for blood pressurewhich can not be obtained during armergometry and was obtained during the rest period betweenstages. Exercise tests were to beterminated immediately if one or more of thefollowing symptoms occurred: 1) chest pain, 2) STsegment depression or elevationof> 1mm, 3) a significant decrease in systolic blood pressureduring exercise(>10 mmHg), and/or 4) other abnormal ECG responses. Once participantscompleted their test they entered a 2 minuteactive rest period where they continued to exercise atapproximately 30-40% of their maximal wattage. Followingactive recovery a passive recoveryperiod of 4 minutes began. Measures of HR and bloodpressure were taken as the participantsrecovered.9.2.1.2. Exercise MeasurementsExpired gas and ventilatory parameters were acquired throughout the incremental armergometer test using a mass spectrometer(Amis 2000, Innovision, Odense, Denmark) allowing forthe determination of submaximal and maximal oxygenconsumption. Continuous measurements ofHR (3-electrode ECG) and oxyhaemoglobinsaturation (Sa02) were obtained. Oxygen saturationwas measured by a pulse oximeter (OhmedaBiox 3740, Louisville, CO) at the pinna of the ear.Values were averaged and recorded every second.Peripheral muscle (biceps brachii and vastus lateralis) oxygenation was assessed noninvasively using a fast spatially resolved NIRS (NIRO-300,Hammamatsu, Phototonics, Japan).37One set of optodes was positioned over the motor point of the medial aspect of the biceps brachii,approximately 6-8 cm from the elbow crease of the right arm. Another set of optodes was placedon the distal portion of the right vastus lateralis. The optodes were affixed in a probe holder thatensures maintenance of distance between the emission and detection probes. The limb waswrapped with black lycra followed by tensor bandages to stabilize the probes and prevent ambientlight from contaminating the NIRS signal. Changes in oxygenated and deoxygenated haemoglobinwere calculated by measuring light attenuation at 775, 810, 850, and 9lOnm wavelengths andanalyzed with an algorithm using the modified Lambert-Beer law. The combination of oxygenatedand deoxygenated haemoglobin, total haemoglobin, is presented as the degree of muscle bloodflow (Boushel et al. 2001). Changes in haemoglobin were calculated relative to resting levels. TheNIRO 300 was calibrated prior to each test. A running average integrated over 10 seconds wasused.A data acquisition system (Powerlab 16/30, ADlnstruments, Colorado Springs, CD) andpersonal computer was used to record continuous ECG, HR, Sa02, and NIRS data.At every third minute of the resting period and during the third minute of each three- minuteexercise stage, measures of Q were assessed non-invasively using inert gas rebreathing (Amis2000, Innovision, Odense, Denmark). During the 1 minute rest interval between exercise stagesparticipants had their blood pressure measured on the arm and indicated their rating of perceivedexertion using the modified Borg scale (see Appendix D).9.2.2. Resting MeasuresAs with other physiological tests, arterial compliance and endothelial function may beaffected by several factors. As vascular function appears to follow the same diurnal pattern asblood pressure (Hypertension Diagnostics 2002) measurements were taken in the morning38between 8:00 and 11:00 AM for all participants. To help control for dietary effects, participants wereasked to fast overnight (8 hours). Participants were also be asked to empty their bladder, to refrainfrom vigorous exercise, smoking, drinking alcoholic or caffeinated beverages, and taking vitaminsupplements at least 8 hours prior to testing. A certified ultrasonographer performed all brachialartery diameter and flow measurements.9.2.2.1. Arterial ComplianceThe non-invasive assessment of large and small arterial compliance was performed usingthe HDI/Pulse Wave CR-3000 Cardiovascular Profilor (Hypertension Diagnostics/Pulse WaveTMCR-3000). This technique, involves 30-second recordings of signal-averaged arterial pulse wavesby applanation tonometry using a surface-residing transducer over the radial pulse of supinesubjects (Resnick et al. 2000). The transducer flattens (applanates) the vessel and produces ameasurable pressure waveform (Hayward et al. 2002; Matthys and Verdonck 2002). The waveformis calibrated by the oscillometric method with a cuff on the opposite arm and a calibration systeminternal to the HDI/Pulse Wave CR3000 CV Profilor (Schillinger et al. 2002). The accuracy of thismethod of obtaining waveforms has been validated in animal and human studies (Hayward et al.2002). A computer-based assessment of the diastolic pressure decay using a modified Windkesselmodel of the circulation separates diastole into two components: large artery compliance(capacitance), measured as the exponential decay of the waveform and small artery compliance(oscillatory) measured as the fluctuations in the waveform that occur on the basic shape of thewaveform (McVeigh et a!. 1999; Arnett et al. 2001). The CVProfilor® (MD-3000 cardiovascularprofiling system, Eagan, MN) used in this study provides a global compliance measure (Pannier etal. 2002). It uses the modified Windkessel model to provide an independent assessment ofcapacitive compliance (Cl), reflecting large conduit arteries, and oscillatory (or reflective)39compliance (C2), reflecting smaller, more peripherally located arteries and arterioles (Finkelsteinand Cohn 1992). The CVProfilor® has proven to be a useful tool in identifying individuals at risk foratherosclerotic events (Grey et al. 2003). The C2 index identifies the presence of endothelialdysfunction in the mircovascular circulation (McVeigh et al. 2001; Hypertension Diagnostics 2002).The Cl index identifies stiffness and atherosclerosis of the aorta and large arteries. In general, theC2 index is more sensitive and shows a decrease in arterial elasticity before the Cl index(Hypertension Diagnostics 2002; Cohn et al. 2004).Measurement of arterial compliance commenced following 5 minutes of supine rest.Measures were taken in triplicate and the closest two values were averaged. The mean coefficientof variation for large and small artery compliance was 0.05 and 0.10, respectively.9.2.2.2. Endothelial FunctionEndothelial function was assessed non-invasively via FMD. Subjects lay supine in a quiet,temperature-controlled room for 10 minutes to allow for blood pressure stabilization.Threemonitoring ECG electrodes were attached to the chest. A 7.5MHz linear arraytransducer attachedto an ultrasound machine (Logic i, GE Medical Systems, Wauwatosa, WI, USA) was used to imagethe brachial artery in a longitudinal section approximately 5 cm proximal to a blood pressurecuffwhich was attached on the forearm just below the antecubital fossa. Upon obtaining a baselinevalue for brachial artery diameter and blood velocity, the cuff on the forearm wasinflated to300mmHg for 5 minutes. Following cuff deflation hyperaemic flow velocity in the brachial arterywas recorded for 25 seconds followed by continuous measurement of brachialartery diameter for 3minutes. After a resting period of 15 minutes, baseline measures of brachial artery diameter wereagain recorded. Then a systemic dose of nitroglycerin (0.3 mg tablet) was administeredsublingually to measure endothelium-independent vasodilation (Higashi et al. 2001; Komai et al.402002) or nitroglycerin mediateddilatation (N MD). Continuous measurements ofbrachial arterydiameter were taken for 6 minutes followingnitroglycen administration. Data collectedduringthese measurements was saved toDVD for analysis offline.Offline vessel diameters of thebrachial artery were measured at baseline and from 45-180seconds after cuff release and for 6 minutesfollowing NTG administration. All measures weretaken at the end-diastolic phase of thecardiac cycle for each heart beat. Five measures of vesseldiameter were taken and averaged for everycardiac cycle. FMD was reported as the greatestincrease in end-diastolic diameter from baselineaveraged from the 3 highest consecutiverecordings. FMD and NMDwere expressed as the maximal absolute value, percentchange frombaseline, and as a FMD/NMD ratio (Chanet al. 2003).9.2.2.3. Quality of Life IndicatorsTo provide insight into psychological well-beingfive questionnaires were employed (seeAppendix A):The Rosenberg Self Esteem Scale (SES) is asubjective self-report measure of global self-esteem. It consists of 10 statements related tooverall feelings of self-worth or self-acceptance.Cronbach’s alpha for this scale is reported at 0.86(Vermillion and Dodder 2007).The Satisfaction with Life Scale (SWLS) allowsindividuals to assess their well-being basedon their own unique criteria without reference to aspecific domain. Among the well-being scales,the SWLS has been used most often with the SCIpopulation (Richards et al. 1999). The SWLS isa subjective questionnairecomprised of 5 items rated on a 7-point Likert scale and hasbeenshown to have desirable psychometric propertieswith a coefficient alpha of 0.87 and correlationcoefficient of 0.82 (Diener et al. 1985).41The Centre for Epidemiological Studies Depression Scale(CES-D) measures thefrequency of 20 depressive symptoms over the past week.Responses are made on a 4-point Likenscale ranging from 0 (rarely or none of the time)to 3 (most or all of the time). Aftainable scoresonthe scale range from 0-60. Scores of 16 or greater indicateincreased risk for clinical depression.With respect to reliability, in the SCI populationthe CES-D has been shown to have aCronbach’salpha of 0.91 and retest reliability of lCC0.87(95% confidence interval (Cl) 0.79—0.93)(Miller etal. 2008).The Medical Outcomes Study 36-item Short Form(SF-36) is the most validatedhealthrelated QOL questionnaire. The SF-36 has beenshown to have a good internalconsistency(Cronbach’s alpha coefficient 0.72—0.98)and intrainterviewer reliability (ICC=0.71-0.99) (Lin et al.2007). The SF-36 is an objective questionnairethat consists of 36 items in 8 scales (GeneralHealth, Physical Functioning, Pain, SocialFunctioning, Role Limitations dueto Physical Problems,and Role Limitations due to EmotionalProblems, Mental Health, and Vitality)that can be clusteredin 2 summary scores for physical andmental health. Designed for use in variousdiagnostic groups,the SF-36 has been used in personswith SCI (Post and Noreau 2005). Thoughits use inindividuals with SCI has been rated asmoderately positive (Andresen et al. 1999)the physicalfunctioning scale has been found to beoffensive to individuals with mobility impairmentsas half theitems make reference to walking or climbing(Andresen et al. 1999).The World Health Organization Qualityof Life assessment (WHOQOL-BREF)is asubjective short form assessment designedto provide information on 4 domains includingphysicalhealth, psychological health, socialrelationships, and environment (WHO1996). The WHOQOLBREF has proven to be an appropriategeneric health-related quality of life measurefor personswith traumatic spinal cord injuries. In this populationthe WHOQOL-BREF has been shownto have42a Cronbach’s alpha coefficientof 0.75-0.87 and with respect tointrainterviewer reliability an ICCof0.84-0.98 (Lin et al. 2007).10. StatisticalAnalysisFor both exercise and measurementof vascular function, datawas analyzed off line foreach participant. Resultswere considered significant atan alpha of p 0.05. Tukey post-hoccomparisons were conductedwhen significant differenceswere observed. Statistical analyseswere performed using SPSS16.Comparisons for exercisemeasures were made betweenindividuals with SCI and ablebodied individuals via 2-way (2x6)mixed model ANOVA.The independent variables includeonebetween-subjects variablewith 2 levels (individuals withSCI, able-bodied individuals) andonewithin-subjects variable with 6 levels(0, 20, 40, 60, 80, and100% watts).Measurement of largeartery compliance, smallartery compliance, flow mediateddilatationand nitroglycerin mediateddilatation were analyzed via 1-waybetween-groups ANOVAs. Theindependent variable for eachANOVA is a between-subjectsvariable with 2 levels (individualswithSCI and able-bodied individuals).All questionnaires wereanalyzed via independent-samples t-test.11. Results11.1. ParticipantsEight able-boded individualsand 8 individuals with SCIparticipated in the study. Therewere no adverse events inresponse to the exercise test orthe measurement of endothelialfunction. We attempted toinclude only those participants with alesion level between T6-T1 2.43However, we were able to includeone participant with a T5 lesion as shenever experiencedautonomic dysreflexia and hada normal HR response to exercise.Another participant with anincomplete T12 lesion whodid not use a wheelchair but instead ambulatedwith the assistance of acane participated in the study.This participant was excluded from analysesbecause of their abilityto walk, which was not representativeof the SCI group and would confuse theinvestigation ofdifferences between groupsin this study. Moreover, the age andgender matched control was aninadequate match for the veryhigh activity level of this individual andwas excluded from analysis.Therefore fourteen participants were leftfor inclusion in the analyses. There wereno significantdifferences between individualswith SCI and able-bodied individualsfor sex, age, BMI, or activitylevel (see Table Ia, b). However individualswith SCI (M=123, SD=8.35) hada significantly higherresting systolic blood pressure thanable bodied individuals (M110, SD9.09;t(12)2.82, p=O.0l6,eta squared= 0.40). The sameholds for diastolic blood pressure with individualswith SCI (M=71,SD=5.96) significantly higherthan able-bodied individuals (M=63, SD5.14; t(12)=2.72,p=0.Ol9,eta squared= 0.38).11.2. Exercise MeasuresMaximal power output was notsignificantly different between individualswith SCI(M=69.29, SD=18.36) and able-bodiedindividuals [M=80.00, SD=26.93,F(1,12)=0.757, p=O.40l;eta squared= 0.059]. A mixedmodel ANOVA was used to examinedifferences in relative andabsolute V02, HR, SV, Q, avDO2,and NIRS measures of blood flow andoxygenation in the armand leg between individualswith SCI and able-bodied participantsat stages of 0, 20, 40, 60, 80,and 100% of maximal exercise.There was no statistically significantgroup by stage interaction forrelative and absoluteV02, HR, SV, Q, and avDO2.Also there was no significant maineffect for group for any of the44same vaables. However effect sizes for all these variables,save avDO2 were moderate to large.Differences between groups grew with able-bodied individualsincreasing to a greater degree at 80and 100% watt stages for V02 and Q (see Figure 2a, b, e).Individuals with SCI had a higher HRthan able-bodied individuals at every stage, but resultswere non significant (see Figure 2c). Theopposite holds for SV, with able-bodied individuals beinghigher at every stage. However the largeamount of variability precluded statistically significant results(see Figure 2d).There was a statistically significant main effect for exercise stagefor all variables (refer toFigure 2a-e; see Table 3 for means and standard deviations).Specifically, for V02, HR, and Q,each stage was significantly higher than the preceding stage (see Figure2a, b, c, e). For SV the100% watts stage was significantly higher than values at 60% watts (see Figure 2d).For avDO2 allexercise stages were significantly higher than 0% watts (see Figure 2f).There was no statistically significant group by stage interaction for NIRS measuresof totalhaemoglobin and oxygenation in the arm and leg between individuals with SCI and able-bodiedparticipants. There was a significant main effect for group in leg oxygenation (see Figure 3c)withable bodied individuals having statistically significant lower oxygenationvalues at 40, 60 80, and100% watt exercise stages compared to individuals with SCI.Though non-significant, able bodiedindividuals had consistently lower arm oxygenation values than individuals with SCI atall stages.Able-bodied individuals experienced higher values of change intotal haemoglobin at all stages,and while statistical significance was notachieved (see Figure 3b) there was a large effect size(eta squared= 0.16).There were statistically significant main effects for exercisestage for total haemoglobinand oxygenation in both the arm and leg. Specifically, for leg oxygenation (see Figure3c), the 80and 100% watt exercise stages were significantly lower from rest,all other exercise stages, and the100% watt stage was significantly lower than the preceding 80% watt stage. Armoxygenation45decreased from baseline until the 60% watt stage before increasing slightly during the 80and100% watt stages (see Figure 3a). Values of arm oxygenationfor all exercise stages weresignificantly different from rest but not each other. For total haemoglobinin the arm there was astatistically significant trend of total haemoglobin increasing with exercise stage (seeFigure 3b).For leg total haemoglobin there was a statistically significant trend of decreasing totalhaemoglobinwith exercise stage (Figure 3d).11.3. Resting Measures11.3.1. Arterial ComplianceA one-way between-groups ANOVA was conducted to explore differences betweenindividuals with SCI and able-bodied controls for large and small artery compliance. Means andstandard deviations are presented in Table 4 and 5. There was no statisticallysignificant differencebetween individuals with SCI (M=19.59, SD=6.74) and able-bodied individuals [M=23.93,SD10.35, F(1 12)=0.865, p=0.37; eta squared 0.07] for larger artery compliance (seefigure 5).There was a statistically significant difference for small artery compliance[F(1 ,12)=5.46,p=O.Oz1;eta squared= 0.31] with able-bodied individuals (M=10.51, SD=1 .69) exhibiting higher values thanindividuals with SCI (M=6.91, SD=3.70) (see Figure 4).11.3.2. Endothelial FunctionA one-way between-groups ANOVA was conducted toexplore differences betweenindividuals with SCI and able-bodied controls for FMD, NMD, and FMD/NMD ratio. There was nostatistically significant difference between groups for FMD [F(1 ,12)=0.00, p=1 .0; etasquared=0.00],NMD [F(112)=0.22, p=O.65; eta squared=0.02], or FMD/NMD ratio[F(112)=0.75, p=0.40; etasquared=0.06]. Refer to Table 5 for means and standard deviations.4611.4. QuestionnairesIndependent samples f-tests were conducted to compare individuals with spinal cord injuryto able-bodied individuals in quality of life via the following questionnaires: the SES, the SWLS, theCES-D Scale, the mental component of the SF-36 and the WHOQOL-BREF.There was no significant difference in self esteem between individuals with SCI (M=25.00,SD=5.48) and able bodied individuals (M=25.57, SD3.60; t(12)=-0.231, p=0.82). The magnitudeof differences in the means was very small (eta squared= 0.004).There was no significant difference in satisfaction with life between individuals with SCI(M=25.00, SD=7.51) and able bodied individuals (M28.14, SD=5.55; t(12)=-0.89, p=0.39). Themagnitude of differences in the means was moderate (eta squared= 0.058).There was no significant difference in depression between individuals with SCI (M=12.57,SD=1204) and able bodied individuals (M=6.71, SD=3.90; t(12)=1.22, p=0.24). The magnitude ofdifferences in the means was large (eta squared=0.10).There was no significant difference in the mental health component of the SF-36 betweenindividuals with SCI (M74.57, SD=22.59) and able bodied individuals (M=83.29, SD=6.26; t(12)=-0.984, p=0,345). The magnitude of differences in the means was moderate (eta squared 0.069).The physical health component of the SF-36 was not scored as individuals with SCI had varyinginterpretations or did not answer questions which required the individual to be able to walk.While able bodied individuals scored higher in all four domains of the WHOQOL-BREF,physical and psychological health, social relationships, and environment, there was no statisticaldifference in physical health [t(12)=-2.01, p=0.07; eta squared=0.25], psychological health [t(12)=-1.08, p=.30; eta squared=0.09], social relationships [t(12)=-1.84, p=0.09; eta squared=0.21], andenvironment [t(1 2)-0.46, p=0.66; eta squared=0.02].47Two individuals with SCI in this investigation were on antidepressant medications at thetime of data collection (see Table 2).12. Discussion12.1. Exercise Measures12.1.1. Cardiorespiratory MeasuresSpinal cord injury can result in two major exercise-related problems: a reduced ability tovoluntarily perform aerobic exercise using large muscle groups and an inability to stimulate theautonomic and cardiovascular systems to support higher levels of aerobic metabolism. Despitethese limitations, in this investigation maximal power output was not significantly different betweengroups. Most exercise studies show that able-bodied individuals have a higher maximal poweroutput than individuals with SCI (Davis 1993) although individuals with low lesion levelscan havemaximal power outputs similar to able bodied persons (Flandrois et al. 1986). In this study, ablebodied individuals had a maximal power output 10 watts higher, a trend which supports the findingfor higher power output in able-bodied persons. The lack of statistical significance is likely theresult of high variability and also due to all SCI participants in the study having lesions below T5,the result being full function of the arms and an intact sympathetic innervation to the heartresultingin a more normal exercise response. Furthermore, some of the decrement inperformance resultingfrom paralyzed trunk and leg muscles could be weighed against local muscle adaptationsindividuals with SCI obtain from using the arms to ambulate and exercise. Also, most of the ablebodied participants if and when they trained aerobically did not do so using the arms.The VO2max for arm ergometry in this study is comparable to values previously reportedfor able bodied individuals and those with SC! (Flandrois et al. 1986; Hopman et al. 1993a; Haisma48et al. 2006). Equality of aerobicpower between individuals with and without SCI who possesssimilar levels of physical activity has rarely been demonstrated(Davis 1993). However thisinvestigation did not reveal differences in aerobic power betweengroups (see Figure 2a, b). Thesmall sample size (n=14) may explain why significantdifferences were not observed. The tendencyfor higher (but non-significant) values in the last 2 exercisestages (see Figure 2a, b) and a largeeffect size (eta squared 0.14) suggestthat differences would be demonstrated with moreparticipants. For example Hooker et al. (1993) found significantdifferences for VO2peak between15 able bodied participants and 13 and 14 high and lowlesion paraplegics, respectively (Hooker etal. 1993). Hopman et al. (1992) found significance difference for VO2peakwith 11 able bodied and11 paraplegic participants (Hopman et al. 1992). A powercalculation (alpha=0.05, power=0.80) forthis study indicates that a total of 34 participants would yield statistical significance.In able bodied individuals, exercise of an aerobic nature results in peripheral arteolardilatation and pumping action of the skeletal muscle. This causes a shift in blood volume,with anexpansion of central blood volume and augmented cardiac output and stroke volume(Tschakovskyet al. 1996). In individuals with SCI damage to sympathetic vascularmuscle innervation in the legsand a loss of the muscle pump during activity causes venousdilatation and pooling of blood in theparalyzed legs and splanchnic area (Hopman 1994; Phillips et al. 1998).This causes a reducedcirculating blood volume and preload to the heart resulting in areduced SV (Jacobs and Nash2004; Myers et al. 2007). This reduced SV is most noticeable inindividuals with high lesions.Individuals with lower lesions are better able to maintain venous return due to an intactsympatheticinnervation to the splanchinc area. However, a smaller SV at restand exercise has also been seenin individuals with lesions below T6 relative to able bodiedpersons (Phillips et al. 1998; Schmid etal. 1998; Jacobs and Nash 2004). The results of the presentinvestigation saw able bodiedindividuals with a higher SV at rest and at all exercise stages,which is in accordance with the49findings of others (Phillips et al. 1998; Jacobs and Nash 2004). However the large amount ofvariability precluded statistically significant results (see Figure 2d). A large to moderate effect size(eta squared= 0.10) suggests that statistical significance would be attained with more participants.A power calculation (alpha=0.05, power=0.80) indicates that a total of 28 participants would yieldstatistical significance.Because of the lower SV often observed in SCI, there must be an increase in HR if Q is tobe maintained. Figure 2c shows that HR was lower in able bodied individuals at all stages althoughresults were non-significant. These trend supports the findings of others (Kinzer and Convertino1989; Hopman et al. I 993a), and likely results from a less efficient redistribution of blood from theinactive lower body to the heart in individuals with SCI (Hopman et al. 1992). Figure 2c (and figure2d) also shows that the mode of Q increase was the same in both groups, i.e. due to an increase inHR while the there was a small increase in SV. Importantly, the highest SV was achieved duringmaximal exercise. This would seem to indicate the basically normal regulation of the heart inindividuals with spinal lesions below T5; however we did not measure parameters such as fillingand compliance of the heart.Although Q was not significantly different between groups (Figure 2e) there was a trendevidenced by a moderate effect size (eta squared= 0.08) for Q to increase to a greater level in ablebodied participants during the higher stages of exercise. Moreover, a higher HR compensated for adecreased SV until the final stages. To discuss these findings in the context of previous work in thefield, several studies (Hopman et al. 1992; Hopman et al. 1993a; Hopman 1994; Jacobs and Nash2004) have found that during upper body exercise, individuals with paraplegia with intactsympathetic innervation of the heart demonstrate, at a given submaximal V02,similar Q comparedwith able bodied persons. However, SV and HR at these similar submaximal work levels aremarkedly different, with individuals with SCI having lower stroke volume and higher HR values at50low, moderate and high exercise intensities (Hookeret al. 1993; Hopman 1994). Though nonsignificant, the trends in our data support these findingsof a lower SV and higher HR in Sd. Thefinding of a lower Q in Sd near and at maximal exercise(figure 2e) suggests that individuals withSCI have a central limitation compared to able bodied individuals.While non-significant, this findingsupports those of most studies investigating central and peripheraladaptations in SCI thatindividuals with SCI have difficulty in inducing a volume loadduring arm ergometry (Jacobs andNash 2004). This is likely in part due to impaired sympatheticoutflow and impaired peripheralvasoconstriction and muscle pump of non-exercising tissue, leading to a decreasedvenous returnand cardiac filling pressure (Myers et al. 2007).At rest, oxygen extraction is approximately 23%. As exercise reaches VO2max around 80to 85% of available oxygen is extracted from the blood which results in an increased avDO2(Saltin1985; Daussin et al. 2007). Arteriovenous oxygen differencein this study (Figure 2f) also increasedsignificantly in both groups from rest to exercise as muscle metabolism increased and theneed foroxygen in working muscle increased. However, avDO2 plateaued for both groupsin the earlystages of exercise. Thus the increase in V02 seen above 40% ofmaximal wattage is notattributable to an increase in avDO2. The implication here is that either the maximal ability of themuscle to take up oxygen had been attained early in the exercise testor that after a certain pointadditional oxygen extraction was not required. However, we know thatlimb blood flow is adjustedat a given power output to be above or below thenormal blood flow level in relation to the deviationin Ca02 as a result of varying Pa02. (Welch 1982; Saltin et al. 1998)This suggests that thevariable that is controlled is oxygen delivery and muscle blood flow is then the means bywhich itcan be adjusted (Saltin et al. 1998). Since skeletal muscle is able to accommodate a flowof 200m1lOOg-1 mm-1 or more during whole body exercise, a Qof 50-60L mm-1 or more would be required toapproach that potential flow in a muscle (Ekblom and Hermansen 1968). Normal values for Qin51highly trained endurance athletesare usually around 30L mm-1(Blomqvist and Saltin 1983; RowelI1986; Gledhill et al. 1994).As a result, it is likely that if more oxygenwere required, blood flowcould continue to increasesince the limit of skeletal muscle bloodflow would not be approached byparticipants in this study. In this study,total haemoglobmn (a surrogatemeasure for blood flow) tothe arm as measured by NIRS(figure 3b) did in fact continue to increasewell after the plateau inavDO2 which wouldseem to indicate that blood flow,determined by central factors, is not alimitation.12.1.2. Near Infrared SpectroscopyAt rest skeletal muscle has ahigh vascular resistance. This is a result ofadrenergicsympathetic stimulation which causesarteriole smooth muscle to vasoconstrict(Seals and Victor1991). At the beginning of exercise initialvasodilation is believed to occur due to awithdrawal ofsympathetic outflow to arteriolesin the working muscles. As exercise progresses,vasodilation ismaintained and increased byautoregulation. The high metabolic rate of theexercising musclecauses local changes such as decreasesin oxygen tension and pH, and increasesin CO2 tension,NO, potassium and adenosine concentrations(Pearson and Vanhoutte 1993) whichresult invasodilation if the arterioles of the workingskeletal muscle. Also, more capillariesare openedduring exercise in working muscle, contributingto the increased blood flow inworking muscle. It isthese processes which help to explainthe increase in total haemoglobin withincreasing workloadin the arms of both groups in this studyas seen in figure 3b. These findingsagree with those ofothers investigating blood flow in armergometry (Ahlborg and Jensen-Urstad1991 a; Ahlborg andJensen-Urstad 1991 b).Though non-significant, total haemoglobmnin the arm was higher acrossstages for ablebodied participants. A largeeffect size (eta squared= 0.16) suggeststhat the lack of significance52was due to a lack of power. A powercalculation (alpha=0.05, power=0.80) for this variableindicates that the addition of 6 participants in each group wouldbe needed to have totalhaemoglobin in the arm achieve statistical significance.This trend towards difference may reflectthe fact that the redistribution of blood flow to the activemuscles during exercise that normallyoccurs in ambulatory individuals is largely absent after SCI(Myers et al. 2007). It has been shownthat at maximal exercise arm blood flow and arm oxygenuptake are significantly higher in rowersthan in able bodied controls (Volianitis et al. 2004).This investigation shows the opposite trend withthose who use their arms to train and ambulate (SCI)having a lower arm total haemoglobin thanable bodied controls. Presumably any local muscular adaptationswere countered by a lack ofskeletal muscle pump and absent or insufficientvenoconstriction to minimize peripheral vascularvolume, causing insufficient venous return, and blunting SV (Myers et al. 2007).While vascular resistance in working skeletal muscle decreaseswith exercise, vascularresistance to viscera and non-exercising muscle increases. Thisis a result of an increase inadrenergic sympathetic output to these areas and is necessary for theregulation of blood pressureduring exercise. Several authors (Kinzer and Convertino 1989;Hopman et al. 1993b) have shownthat, due to a loss of sympathetic vasoconstriction in the legs,blood redistribution from the lowerlimbs was impaired in those with Sd. Figure 3d shows that totalhaemoglobin did indeed decreasewith exercise of increasing intensity. However, there was nosignificant difference between groupsin change in leg total haemoglobin during theexercise testing. This seems to contradict the trend ofa lower increase in total haemoglobin in theexercising arms of SCI participants as there was not aconcomitant difference between groups (Figure 3d).However we should note that splanchinc bloodflow was not accounted for, the nature of NIRS measurementprevents knowledge of absolutevalues which could be different between groups (de Groot etal. 2006).53The decrease in oxygenated haemoglobin in the arms (see figure 3a)from rest to the first3 stages of increasing exercise intensity suggests a greaterrelease of oxygen by haemoglobin viathe Bohr effect. There is a levelling off of deoxygenation in theexercising arms observed in bothSCI and able bodied participants from 60 to 100% of maximalwattage despite a continuedincrease in total haemoglobin (see figure 3b). These findingsare similar to that found in otherresearch investigating muscle deoxygenation during armergometry (Muraki et al. 2004) andsuggests that the oxidative ability in the working musclereached a limit, not that oxygen supply tothe working muscle was inadequate. If muscle bloodflow increased beyond the muscle metabolicrequirement, the concentration of O2Hb would be expected to increase due to a lower 02extraction(DeLorey et al. 2003). This suggests a peripheral limitation to exercise.As exercise intensity progressed throughout the exercise test leg oxygenation decreasedfor both individuals with SCI and able bodied controls (Figure 3c). Concentration changesinoxygenation are dependent on the dynamics of the equilibum between tissue 02demand andsupply (Kawashima et al. 2005). Because the leg musculature was notbeing used for the exercisetest, we may assume that 02 demand did not increase in the vastuslateralis. Thus the decrease inleg oxygenation is believed to reflect a decreased supply of 02 to the leg, a result of increasedneed of the exercising arms.Able bodied participants experienced a significantly greater decrease in oxygenatedhaemoglobin in the leg during the exercise test than individuals withSCI (Figure 3c). A possiblereason for this difference may lie with the muscle contractions thatoccur in the leg musculature asexercise intensity reaches higher levels. While all able bodiedparticipants were asked to minimizemovement of the legs during the test they likely did recruit theirlegs as stabilizers to increaseleverage with exercise at higher wattages.5412.2. Resting MeasuresThis study indicates that individuals with SCI have poorer small artery compliance thanable-bodied control participants (figure 4). This trend is in agreement with previous research thatshows decreased arterial compliance in persons with paraplegia (Wecht et al. 2004; Zbogar et al.2008). In individuals with SCI the extreme inactivity resulting from paralysis and the loss ofsupraspinal sympathetic vascular control are both cited as potential factors for poor arterialcompliance in the leg (De Groot et al. 2005). Arterial compliance in this study was measured at theradial artery and not in the leg. However, the applanation tonometer used in this study provides aglobal assessment of arterial compliance, and not strictly the compliance of the local (radial artery)vasculature. This is because the tonometer employs a Windkessel model of the circulation wherethe diastolic pressure contour is a function of resistance, compliance, and inertance of an isolatedarterial system. The site of measurement therefore is theoretically unimportant, because thesystem is closed and the pressure is transmitted within the system (Cohn et al. 2004). If this wasnot the case we might expect to see individuals with SCI have higher arterial compliance due to themuch higher use of the arms on a daily basis relative to able-bodied individuals.The determinants of arterial compliance differ between large and small arteries. This helpsexplain why differences in the study participants were not seen in large artery compliance (seefigure 5) while there was a significant difference in small artery compliance between groups. Apower calculation with alpha at 0.05 and power at 0.80 suggests that a sample size of 61 would berequired to find significance for large artery compliance between groups. However, it was notexpected that large artery compliance would be significantly different between groups based onprevious research (Grey et al. 2003) and due to the fact that generally, small artery compliance isconsidered a better predictor of early cardiovascular disease as it often shows a decrease before,and to a greater degree than large artery compliance (Hypertension Diagnostics 2002). In large55arteries, collagen and elastin are the major determinantsof function (Cohn et al. 2004). In smallerarteries and arterioles, NO released from the endotheliumplays a significant role in determiningcalibre and compliance via its actions on smooth muscle (Cohn etal. 2004). Therefore, it followsthat a reduced compliance of the small arteries and arteriolesis (in part) the result of endothelialdysfunction. However, recent evidence shows that arterial complianceis not necessarily correlatedwith endothelial function (Westhoff et al. 2007) despitethe fact that both arterial compliance (Greyet al. 2003) and endothelial function (De Groot et al. 2005)decrease with cardiovascular diseaseprogression. Results from this study seem to reflect the findings of Westhoff et al. (2007)since nostatistically significant differences were found in endothelial function (avery small effect size forFMD (eta squared= 0.00) suggests that the lack of significance was not due to alack of power)between groups while a difference in small artery compliance was found between groups.Otherresearch (Nair et al. 2005) has shown that vascular compliance as assessed by pulsewaveformanalysis correlates better with cardiovascular risk factors than does FMD as assessed byhighresolution ultrasound. The findings of this study suggest that pulse wave analysis maybe apreferred method of cardiovascular health assessment; in addition to supporting the significantdifference in small artery compliance seen in other studies,pulse wave analysis is less operatordependent and simpler to use.12.3. Quality of LifeStudies comparing QOL in individuals with SOt and able-bodied individuals showthat SOtgroups score significantly lower (Dijkers 2005). However inthis investigation, although able-bodiedindividuals tended to score higher on all questionnaires, nosignificant differences were foundbetween individuals. Other studies have shown that whilethose with 501 score significantly lower,differences are not as large as might be expected (Dijkers 2005;Post and Noreau 2005). Indeed,56some literature (Eisenberg and Saltz 1991; Chapin etal. 2004) shows that QOL following SCIcovers a wide range of scores from well below to scores that approach or surpasshealthypopulation averages.It is possible that the subjective nature of most of the questionnaires in this studycontributes to the lack of significance and moderate effect sizes for some questionnaires. Indeed,some domains of subjective QOL are found to be equal to or even higher than the generalpopulation (Eisenberg and Saltz 1991; Post and Noreau 2005). Subjective QOL questionnairesmeasure outcomes through the individual’s point of view and results can vary greatly betweenindividuals. In the SCI population there are many potential predictors of subjective QOL including,but not limited to, environmental issues, community reintegration/participation factors such asemployment, interpersonal relationships, and social functioning, phychological factors such asloneliness and perceived control on life, health-related factors, injury-related factors, pain anddemographics (Boschen et al. 2008). These factors may have had an impact on increasing thevariability that was seen in the answers of individuals with SCI in this study.The large effect size and trend towards significance for physical health and socialrelationships in the WHOQOL suggests that a larger sample size would show individuals with SCIto be significantly lower in these domains. The trend for lower scores in the social relationshipdomain of the WHOQOL is owing to two factors: 1) several individuals expressed dissatisfactionwith their sex life; indeed the literature shows sexual function is very often impaired due to spinalcord injury (Anderson et al. 2007), and 2) one individual had recently lost their circle of friends asthose friendships were centered on a sport in which he can no longer participate. Power analysisusing an alpha at 0.05 and a power of 0.80 indicates that we would begin to find statisticalsignificance with an additional 5 participants in each group.57Quality of life has been shown to be enhanced by meaningful relationships; theassumption of responsibility for, and opportunity to exert control over, one’s own life; and the abilityto engage in personally meaningful occupations (Hammell 2004a). Individuals with lower spinallesions are more independent than their tetraplegic counterparts. Also, most participants in thisstudy were engaged in personally meaningful occupations and their interest in volunteering for thisresearch study lends itself as evidence of their taking initiative and having control over their ownlife. Studies of tetraplegics (Bach and McDaniel 1993; Hammell 2004b) have been able to showsignificant differences in QOL, however participants with spinal injury in theses studies numberaround 15. Our study included half that number of individuals and participants were paraplegic nottetraplegic. Because of this low number and due to the higher function of paraplegics, the nonsignificant results for questionnaires used in this study are not surprising.The effect of antidepressant medication on QOL assessments shows that followingtreatment with medication there is an improvement in social function as measured by tests such asthe SF-36 (Kennedy et al. 2001). This further complicates the assessment of psychologicalmeasures of quality of life in this study such as the CES-D, SES, and psychological domains withinthe SF-36 and WHOQOL-BREF. Two individuals with SCI in this study were taking antidepressantswhen questionnaires were administered. Any improvement which resulted from this medicationwould presumably decrease the likelihood of finding a significant difference between groups or alarger effect size for questionnaires such as the CES-D.13. ConclusionWith respect to assessment of QOL, this investigation lends support to other findings.Studies investigating physical function and limitations which result from physical problems show58that the SCI population scores lower compared to able-bodied persons(Leduc and Lepage 2002;Post and Noreau 2005) and in our study the trend for a difference inthe physical domain of theWHOQOL supports this well established finding. This study alsoinvestigated other measures ofemotional QOL assessment such as depression, satisfaction with life, and psychological health asassessed by the WHOQOL and found no trends towards statistical significance. This findingagrees with those of others that show scores of mental health, vitality, and rolelimitations due toemotional problems and mental health are not lower in SCI than in the general population (Leducand Lepage 2002; Post and Noreau 2005).In the assessment of vascular compliance, this study confirms our previous findings(Zbogar et al. 2008), showing that small artery compliance is lower in individuals with SCI. Thesefindings indicate that the assessment of arterial compliance appears to be an important method forthe noninvasive, early detection of cardiovascular disease following Sd. This studyalso supportsthe finding of Westhoff et al. (2007) who showed that arterial compliance was not correlated withendothelial function and also that perhaps arterial compliance assessment correlates better withcardiovascular risk than does FMD as assessed by ultrasound (Nair et aT. 2005).Investigation of the cardiovascular response to exercise of increasing intensity reflectstrends found in other research (RoweIl 1986; Gledhill et al. 1994) showing increases in V02,HR,SV, and Q with increasing exercise intensity. Although statistically significant between groupdifferences were not found in this study, our results yielded trends whichhave been documentedby others (Hopman 1994; Nash et aT. 1996; Phillips et al. 1998;Myers et aI. 2007) showing that SVis lower in SCI and that HR compensates for this and that ablebodied individuals have a higherVO2peak, and Q.The significant finding yielded by NIRS shows that able bodied and SCIindividuals differedin oxygenation of the lower leg. This may be a result of muscle contractions thatoccur in the leg59musculature as exercise intensity reaches higher levels. Despite being asked to minimizemovement of the legs during the test able bodied participants likely did recruit their legs asstabilizers to increase leverage with exercise at higher wattages.Our finding that total haemoglobin in the working muscle continued to increase throughoutthe exercise test suggest that blood flow was not a limiting factor in graded exercise using armergometry for both able bodied and SCI individuals. These findings which reflect those of Muraki etal. (2004) suggest that because the decrease in oxygenated haemoglobin leveled off duringexercise while blood flow increased throughout all stages a limitation to exercise in both ablebodied and SCI groups lies in the muscle. However this study also suggests that individuals with501 may, relative to able bodied persons, have a central limitation which is evidenced by a trendtowards lower Q as exercise reached maximal levels, As per the Fick equation, V02 is affected byQ and the lower Q in individuals with SCI results in a lower VO2max for individuals with SCI.14. LimitationsA small sample in this investigation limits the strength of statistical findings in the presentstudy. Nevertheless, several studies examining exercise response in individuals with SCI havefound statistically and clinically relevant results with sample sizes of 5 to 9 individuals (Hjeltnes1977; Flandrois et af. 1986; Bhambhani et al. 2000).The large amount of variability found in cardiovascular responses to exercise could resultfrom several factors. Most able-bodied participants in this study did not aerobically train using theirupper limbs and many had never used an arm ergometer. Habituation for all participants to thismethod of exercise was limited to the 0.5 hours preceding the actual exercise test. While muchhabituation is not required for arm cycle ergometry relative to wheelchair ergometry, able bodied60persons still varied greatlyin the capability of the arms to reach higherwattages. This variabilitylikely translated into very differentvalues for factors such as SV which exhibited alarger amount ofvariability than in individuals withSCI across all stages (see table 3).Measures obtained in this study were determinedindirectly. For example resting andexercise SV was indirectly determined viaacetylene rebreathing. Moreover, avDO2 wasindirectlymeasured as V02divided by Q.However, we anticipate that recruitment wouldhave been moredifficult and fewer individualswould have agreed to enroll in the study if measures weredirect andtherefore invasive.With respect to potential central and peripherallimitations to exercise, only a handful offactors could be measured in this study:SV, HR, avDO2, total haemoglobin and muscleoxygenation. We are unable to comment on otherpotential sources of limitation as discussed insection 5.1 or offer, for example, further insight intohow factors contributing to SV (e.g.investigation of systolic or diastolic function of theheart which would be afforded by cardiacultrasonography) respond to exercise andhow they differ between individuals with SCI and ablebodied controls.The use of NIRS is restricted to a few cubic centimetresof muscle. We can only speculateon the nature of change in total haemoglobin andoxygenation in other areas of both the workingand non-working limb measured in thisstudy. It has been shown that NIRS values candiffersignificantly within the same muscle (Kennedy et al.2006) and data from studies on other speciesindicates that muscle perfusion is farfrom homogeneous (Piiper and Haab 1991). Theabsorptionspectra of myoglobin and haemoglobin overlap,with myoglobin composing approximately 10%ofthe signal, and therefore NIRS does notdifferentiate between these signals in vivo (Boushel,Langberg et al. 2001). Also, quantifying the absoluteconcentration of any chromophores in thetissue is not possible as the path-lengthof the light from emitter to detector is unknownand there is61no distinction between absorbed orscattered light. It must be recognized thatthe measure of totalhaemoglobin which we tookas a measure of blood flow can be influenced notonly by increasedblood flow, but also by venous obstruction orincreased haemoglobin concentration. Also anincrease in oxygenated haemoglobincan indicate increased arterial inflow,increased oxygensaturation or an increased concentrationof oxygenated haemoglobin (Raisis 2005).Despite these limitations, NIRS doesprovide important information regarding trendsinmuscle oxygenation during exercise andrecovery.Finally, we can only speculate that isometric contractionand leg movement in able bodiedindividuals contributed to the difference indecline of oxygenated haemoglobin between groupsduring arm ergometry. The use of EMG wouldhave allowed us to comment more definitivelyonthis issue.TableIa.Particloantcharacteristics(soinalcordiniuredAerobicLesionASIAParticipantGenderAge(y)BMISBPDBPActivityTILevelgrade(dayslweek)1-SdM1922.61206830.67T11/12A3-SdM4528.412172615T718A4-SdM3124.211767111T6A5-SdF3718.611869212T12A6-SdM3924.711766217T6A7-SdF3320.113883029T5A8-SdM2623.71327611T7AMean32.923.2123.171.22.112.2SD8.63.28.46.02.09.8Tablelb.Participantcharacteristics(ablebodied)AerobicParticipantGenderAge(y)BMISBPDBPActivity(dayslweek)I-ABM1824.01125843-ABM4522.11086844-ABM3124.61116215-ABF4223.81166336-ABM3925.01026617-ABF3220.8975648-ABM2925.4125701Mean33.723.7109.963.12.6SD9.21.69.15.11.5BMI=bodymassindex,TI=timesinceinjury,SBP=systolicbloodpressure,DBP=diastolicbloodpressure,SD=standarddeviation62Table2.ParticiDantmedicationsParticipantMedicationsDosageUsagePossibleCVSideEffectPrevalenceofCVEffect1-SCIWarfarin5mgix/dayanticoagulantsystemicatheroemboli;cholesterolmicroemboli3-SCInone----4-Sdnone----5-Sdnone----6-SCICodeinepmanalgesichypotensionrareVenlafaxine37.5mglxldayantidepressanttbloodpressure3%7-Sdnone----8-SCIGabapentin400mg3xldayneuropathicanalgesicvasodilation;hypertension1%hypotension,hypertension,tachycardia,palpitation,Nortriptyline20mgix/dayantidepressantmyocardialinfarction,arrhythmias,heartblock,strokeBaclofen20mg4xldayanti-spasticityhypotension0to9%Sennosides12mglxldaybowelstimulantnone-CV=cardiovascular;pm=accordingtoneed6364Table 3. Descriptive Statisticsfor aerobic power, HR, SVcardiac output, and avDO2duringthegraded exercise test.V02 (Llmin)StageAB(/o watts)0 0.3 ±0.1 0.3 ± 0.120 0.7 ± 0.20.8 ± 0.140 1.0 ± 0.31.1 ± 0.260 1.2 ± 0.31.3 ± 0.380 1.5 ±0.4 1.8 ± 0.5100 1.7 ±0.4 2.1 ± 0.6HRStageAB(/o watts)0 76.9 ± 15.5 71.6± 11.720 97.0 ± 18.190.7 ± 21.540 116.9 ± 14.1110.4 ± 23.060 148.3 ± 12.3134.4 ± 19.980 165.4 ± 12.6162.0 ± 17.2100 178.0 ± 10.0 171.3± 11.4QStageSCI AS(/o watts)0 6.0 ± 1.46.4 ± 1.320 7.7 ± 2.17.8 ± 1.840 9.3 ± 2.310.2 ± 2.360 11.2 ± 2.312.5 ± 2.480 13.0 ± 3.016.3 ± 5.5100 15.8 ± 3.418.0 ± 5.7V02 (mllkg!min)StageSd AB(/o watts)0 4.1 ± 0.44.4 ± 0.620 10.3 ± 1.310.4 ± 1.040 14.2 ± 2.2 14.5± 2.860 17.3 ± 2.418.4 ± 2.980 20.9 ± 3.125.1 ± 6.0100 23.7 ± 2.728.6 ± 5.7svStageAB(% watts)0 79.9 ± 22.593.6 ± 29.120 81.3 ± 23.0 92.0± 36.640 80.9 ± 23.6 96.4± 32.660 76.8 ± 20.094.4 ± 24.280 80.0 ± 22.7100.5 ± 30.4100 89.1 ± 20.5105.2 ± 32.0a-vDO2(milL)StageSCI AS(/o watts)0 51.1 ± 11.4 50.0± 4.920 101.9 ± 33.1 99.8 ±17.840 113.6 ± 26.8 104.3 ±13.860 112.1 ± 22.0107.8 ± 6.080 116.7 ± 19.5 113.8± 15.7100 108.4 ± 14.1 117.5± 11.3V02= aerobic power, HR= heartrate, SV= stroke volume, Q= cardiacoutput, a-vDO2=arteriovenous oxygendifference, SCI= individualwith spinal cord injury, AB= able-bodiedindividual. Values are means±SD.65Table 4. Descriptive statisticsfor arterial compliance in individualswith SCI and able-bodiedindividualsGroup Mean SDF Sig. eta’Small Artery ComplianceSCI 6.91 3.705.46 0.04 0.31AB 10.51 1.69Large Artery ComplianceSCI 19.59 6.74 0.860.37 0.07AB 23.93 10.35Table 5. Descriptive statistics forendothelial function in individualswith SCI and able-bodiedindividualsGroup Mean SDF Sig. eta’FMD%SCI 6.84 4.31 0.00 0.990.00AB 6.82 3.54NMD%SCI 22.74 9.65 0.220.65 0.02AB 24.66 4.92FMD/NMD ratioSCI 0.91 0.08 0.750.40 0.06AB 0.88 0.06FMD flow mediateddilatation, NMD= nitroglycerine mediateddilatation66Figure 1. Atherosclerosis timelineTaken from Pepine CJ. Am J Cardiol. 1998;82(suppl 104)67Figure 2a-f. Cardiovascular and aerobicresponses to incremental exercisetest2a2bAerobic PowerAerobic Power403.5___________352.5 —— Sd30 _.—sctl-0--0)______252.0201.5S. 0o 15Is 20100.5 S______________________________00.0O 20 40 60 00 1000 20 40 60 80 100Watts (%)Watts (%)2c2dHeart RateStroke Volume200160150 —.— so140160‘5ISOK1400)C 105a 125t1008080606040________________________________________________________________400 20 40 60 80 1000 20 40 60 80100Watts 1%)Watts (%)2e2fCardiac OutputArteriovenous Oxygen Difference25 16014020120-J15C0losa0c’.1 6010gCa60C)540a200 20 40 60 80 iso0 20 40 60 80 100Watts (%)Watts(%lmean±SD;*significantly different from previousstage (p < 0.05)Figure3a-d.Muscletotalhaemoglobinandoxygenationresponsetoincrementalexercisetest.3a05ArmO2Hb3b—.—sd—0—AB0.050.4 0.2 0.0C)-0.4 -0.6 -0.8.-1.0 -1.2 -14ArmTotalHb02040Watts(%)LegO2Hb6080100t02040Watts(%)LegTotalHb60801003c1.03d0.5 0.0E[05-2.0 -2.5020406080100020Watts(%)mean±SD;*significantlydifferentfrom0%watts(p<0.05);tsignificantlydifferentfromable-bodiedindividuals(p<0.05)40Watts(%)6080100680‘OsooU!IdwoDiiwsoICDaCD0I.m0Cl)C)CDxBI:1eousdwoo,cjei.iee6iejgeinI5ijC,)30>CDmCD0C)F0303zCDx-CCt7969eousdwoo,cjeijehewsvejn6ijeoue!IdwoD,c.ie.ive6ei0ItI7015. 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A conceptual model ofpatient outcomes.” Jama 273(1): 59-65.Wilson, J. R., D. M. Mancini, et al. (1989). “Noninvasive Detection of Skeletal-MuscleUnderperfusion with near-Infrared Spectroscopy in Patients with Heart-Failure.” Circulation 80(6): 1668-1674.Yen, M. H., J. H. Yang, et al. (1995). “Chronic Exercise Enhances Endothelium-MediatedDilation in SpontaneouslyHypertensive Rats.” Life Sciences 57(24): 2205-2213.Zbogar, D., J. J. Eng, et al. (2008). ‘The effects of functional electrical stimulation leg cycle ergometry trainingonarterial compliance in individuals with spinal cord injury.” Spinal Cord 46(11): 722-6.7916. AppendicesAppendix Al:Satisfaction with Life Scale(SWLS)The following five statementsare very broad and require you tothink about your life in generalwithout reference to anyparticular area of your life. The questionspertain to how you feel aboutyour life right now. You many agreeor disagree with each of the five statementsby placing anumber between I and 7on the line beside each statement.Please be open and honest in yourresponding and use the followingscale to guide your responses.1 2 34 5 67Strongly Disagree SlightlySlightly Agree StronglyDisagree DisagreeAgreeAgree1. In most ways my lifeis close to my ideal._____2. The conditions of mylife are excellent.3. I am satisfied with mylife.4. So far I have gotten the importantthings I want in life.5. If I could live mylife over, I would change almostnothing.80Appendix A2.Rosenberg Self-EsteemScaleThe scale is a tenitem Likert scale withitems answeredon a four point scale- from strongly agreeto strongly disagree.The original samplefor which the scalewas developed consistedof 5,024High School Juniorsand Seniors from 10randomly selectedschools in New York State.Instructions: Belowis a list of statementsdealing with yourgeneral feelings aboutyourself. If youstrongly agree,circle SA. If you agreewith the statement,circle A. If you disagree,circle D. If youstrongly disagree,circle SD.1. On the whole,I am satisfied withmyself. SAA DSD2.*At times, I thinkI am no good at all.SA ADSD3. I feel that Ihave a number of goodSA ADSDqualities.4. I am able to dothings as well as mostSA AD SDother people.5,*I feel I do nothave much to be proud of.SA ADSD6.*I certainly feeluseless at times.SA ADSD7. I feel thatI’m a person ofworth, at least on SAA DSDan equal planewith others.8.*I wish I couldhave more respectfor SAA DSDmyself.9*All in all, I am inclined tofeel that I am aSA AD SDfailure.10 I take a positiveattitude toward myself.SA AD SD81Appendix A3:CES-D ScaleBelow is a list of the ways youmight have felt or behaved. Please tell mehow often you have feltthis way during the past week.During the pastweek:1. I was bothered by things1 2 34that usually don’t bother me.Rarely or None of Some or Little of the Occasionallyor a Most or All of thethe Time Time Moderate Amountof Time Time(Less than 1 day) (1-2 days) (3-4 days)(5-7 days)2. I did not feel like eating; my1 2 34appetite was poor.Rarely or None of Some or Little of the Occasionallyor a Most or All of thethe Time Time ModerateAmount of Time Time(Less than 1 day) (1-2 days) (3-4 days)(5-7 days)3. lfeltthatlcouldnotshake1 2 34off the blues even with helpRarelyorNoneot SomeorLittleofthe OccasionallyoraMostorAllofthe. .the Time Time ModerateAmount of Time Timefrom my family or friends. (Less than 1 day) (1-2 days) (3-4 days)(5-7 days)4. lfeltthatlwasjustasgood1 2 34as other people.Rarely or None of Some or Little of the Occasionallyor a Most or All of thethe Time Time ModerateAmount of Time Time(Less than 1 day) (1-2 days) (3-4days) (5-7 days)5. I had trouble keeping my1 23 4mind on what I was doing.RarelyorNoneof SomeorLittleoftheOccasionallyora MostorAllofthethe Time Time ModerateAmount of Time Time(Less than 1 day) (1-2 days) (3-4days) (5-7 days)6. I felt depressed1 23 4Rarely or None of Some or Little of theOccasionally or a Most or All of thethe Time TimeModerate Amount of Time Time(Less than 1 day) (1-2 days)(3-4 days) (5-7 days)7. lfeltthateverythingldid1 23 4was an effortRarely or None of Some or Little of theOccasionally or a Most or All of the. theTime Time ModerateAmount of Time Time(Less than 1 day) (1-2 days)(3-4 days) (5-7 days)8. I felt hopeful aboutthe 12 34futureRarely or None of Some or Little of theOccasionally or a Most or All of thethe Time TimeModerate Amount of Time Time(Less than 1 day) (1-2 days)(3-4 days) (5-7 days)9. I thought my life hadbeen a 1 23 4failureRarely or None of Some or Little of theOccasionally or a Most or All of thethe lime TimeModerate Amount of Time Time(Less than 1 day) (1-2 days)(3-4 days) (5-7 days)10. lfeltfearful.1 23 4Rarely or None of Some or Littleof the Occasionally or a Most or All ofthethe Time TimeModerate Amount of Time Time(Less than 1 day) (1-2 days)(3-4 days) (5-7 days)11. My sleep was restless.1 23 4Rarely or None of Some or Littleof the Occasionally or a Most orAll of thethe Time TimeModerate Amount of Time Time(Less than 1 day) (1-2 days)(3-4 days) (5-7 days)(sAepz-9)(sAp-)(sAep-[)(Aep[ueqjss91)9W!±eWJjoUflOWyjJpOvJO1ILJjJOJJOISOINEJOiciuoiseoo8IJJOflflJOGWOJOUOJOIJEj7£1.a15oupincoi(sApL-c)(sXep-)(sXep-)(Aepueqssøl)9w!!8U!J.JOJUflOW’eejapo8W!±9W!!1II94JJO‘‘JOJSOJOAJ9UOiSeOO914JJOeflfl100W09JO9UONJOAieJej.owo)ffls!peldoodeqI61.(scepL-9)(sXep-)(sacep-)(Aepuesso-)9W!!9W!!JJUflOW9eJ9POSW!!9W!!8419114JOJJOjSO9JOA,I9UO!Se0009111JO91W]JO8WOSJO9UOJoAI9JeT7£1.pBSjO•91.(stepL-c)(sIep(sAep-jj(Aep[ueqss9])OWIj9W!!JO4UflOW9J9J3OJ8W!J.8114944JO4JO4SOJ8JOXIieuoiSeO3Q944JO9144!]108W05JO9UONJOXiate17£1.sheds6U!/cJoPILI.(sAepL-g)(sAep-)(sAep-)(Aepueqsso])8W!!9W!!JO1UflOWO48J8POJOW!!OW!!844944JOflJO1SOJ8JOXIIeuO!S800 09144JOIfl!]JOOWOSJOOUONioAieJej7£I.epeAo[ueI91.(sXepL-s)(sAepi-E)(scep(AepueqJssi)9W!!OW!!JO4UflOW8J8O44OW!!8W!!81448144JOIVJOJSO4AJ9JOAIIeuO!seoDO8144JO9144!]JO8WOSJO8UONJOAi9Je£i.AipuepjunOJMeldoed91.(sAepL-c)(sXep-)(sAep-Li(Aepu941ssojOW!!OW!jJOJUflOWV849J8PO4j9W!j.OW!!81149141JOflVJO4SO8JOAIIeUo!SEO8144JO9144!]JO8W09JO8UO4’JJOAi9ie17£I.ieuoi1191I171.(sAepL-9)(sxep-)(sAep-)(Aepueqsse])8W!!OW!!JOIhiflOWy9j8J9O8W!!9W!!91148144JOflyJOISO4AJ910XIIOUO!Se00 0844JO8j44!]JO9WOSJO9UONJOXIOJEd17£i.IBnsnueqssePeiiI(sAepL-c)(sAep,-E)(sAep-j,)(,cepueqsse])OUJ!!OWJJOIUnOWYO48J8POOW!!OW!!81418144JOflJO1SOVJ810II8UO!S8OoO841JO0444!]JO9WOSJO8UONJOXIOJBdv£1.AddeqSBMI1.83Appendix A4:Quality of Life Questionnaire (SF-36)1. In general, would you say your health is:[IIExcellentIVery Good3 4 5Good Fair Poor2. Compared to one year ago, how would you rate your health in general now?1 2 3 4 5Much better than a Somewhat better About the same as Somewhat worse Much worse than ayear ago than a year ago a year ago than a year ago year ago3. The following items are about activities you might do dung a typical day. Does your healthnow limit you in these activities? If so, how much?1 2 3yes, limited a lot yes, limited a little No, not limited at alla. vigorous activities (e.g., running, lifting heavy objects, participating in strenuous sports)_______________b. moderate activities (e.g., moving a table, pushing a vacuum cleaner, bowling, playing golf)___________c. lifting or carrying groceriesd. climbing several flights of stairs_______________e. climbing one flight of stairs___________________f. bending, kneeling, or stooping________________g. walking more than a mile_____________________h. walking several blocks_______________i. walking one block__________________j. bathing or dressing yourself__________________844. Duringthe past 4weeks, haveyou had anyof the followingproblems withyour work orotherdaily activitiesas a resultof your physicalhealth?a. cut downthe amountof time youspent on workor other activitiesYes Nob. accomplishedless than youwould likeYes Noc. were limitedin the kind ofwork or otheractivitiesYes Nod. had difficultyperforming thework or other activities(e.g., it took extraeffort)Yes No5. During thepast 4 weeks,have you had anyof the followingproblems with yourwork or otherregular dailyactivities as aresult of anyemotional problems(such as feelingdepressed oranxious)?a. cut downthe amount of timeyou spent on workor other acvitiesYes Nob. accomplishedless than youwould likeYes Noc. didn’t dowork or other activitiesas carefully asusualYes No6. During thepast 4 weeks,to what extenthas your physicalhealth or emotionalproblemsinterfered withyour normalsocial activities withfriends, family, neighbors,or groups?12345Not at allSlightlyModeratelyQuite a BitExtremely7. How muchbodily pain haveyou had duringthe past 4 weeks?123456NoneVery MildMildModerateSevere VerySevere8. During thepast 4 weeks,how much did paininterfere withyour normal work(including bothwork outsidethe home andhousework)?12345Not at allSlightlyModeratelyQuite a BitExtremely859. These questions are about howyou feel and how things have been with youduring the past 4weeks. For each question, please give theone answer that comes closest to the way you havebeen feeling. How much of the time duringthe past 4 weeks...1 2 34 5 6All of the time Most of the A goodbit of Some of the A little of the Noneof thetime the time timetime timea. Did you feel full of pep?______________b. Have you been a very nervous person?________c. Have you felt so down in the dumpsthat nothing could cheer you up?______________d. Have you felt calm and peaceful?______________e. Did you have a lot of energy?_________f. Have you felt downhearted and blue?__________g. Did you feel worn out?______________h. Have you been a happy person?i. Did you feel tired?___________10. During the past 4 weeks, how muchof the time has your physical health or emotionalproblemsinterfered with your social activities?1 2 34 5All of the time Most of the Some of theA little of the None of thetime time timetime11. How True or False is each of the followingstatements for you?1 2 34 5Definitely True Mostly TrueDo Not Know Mostly False Definitely Falsea. I seem to get sick a little easier thanother people________b. I am as healthy as anybodyI know____________c. I expect my health to get worse________d. My health is excellent________86Appendix A5:The World Health Organization Quality of Life (WHOQOL)— BREFThe following questions ask how you feel about your qualityof life, health, or other areas of yourlife. I will read out each question to you, along with the response options. Pleasechoose theanswer that appears most appropriate. If you are unsure about whichresponse to give to aquestion, the first response you think of is often the best one.Please keep in mind your standards, hopes, pleasures and concerns. We askthat you think aboutyour life in the last four weeks.NeitherVery poor Poor poor nor Good Very goodgoodHow would you rate your quality1 2 3 4 5of life?Neithersatisfied VeryVeryDissatisfied Satisfieddissatisfied nor SatisfieddissatisfiedHow satisfied are you with your1 2 3 4 5health?The following questions ask about how much you have experienced certain things in the last fourweeksA AnNot at all A little moderate Very much extremeamount amountTo what extent do you feel that5 4 3 2 1physical pain prevents you fromdoing what you need to do?How much do you need any5 4 3 21medical treatment to function inyour daily life?5 How much do you enjoy life? 1 2 34 5To what extent do you feel youri 2 3 4 5life to be meaningful?87ANot at all A little moderate Very muchExtremelyamount—7- How well are you able to1 2 3 45concentrate?How safe do you feel in youri 2 3 45daily life?How healthy is your physicali 2 3 45environment?The following quesons ask about how completely youexpeence or were able to do certain things inthe last four weeks.Not at all A little Moderately MostlyCompletelyZ!Do you have enough energy for1 2 3 45everyday life?.Zii Are you able to accept youri 2 3 45bodily appearance?Z Haveyouenoughmoneytomeet1 2 3 45your needs?‘ How available to you is theinformation that you ineed in1 2 34 5your day-to-day life?z14 To what extent do you have the1 2 34 5opportunity for leisure activities?NeitherVery poor Poor poor norGood Very goodgoodZ How well are you able to get1 2 34 5around?88NeitherVeryDis atisfiedsatisfiedSati fedVerydissatisfiedSnor ‘SatisfieddissatisfiedHow satisfied are you with your1 23 4 5sleep?How satisfied are youwith yourability to perform your dailyliving1 23 45activities?How satisfied are you withyour1 23 45ability for work?i How satisfied are you with1 23 45yourself?How satisfied are you withyouri 23 45personal relationships?How satisfied are you withyouri 23 45sex life?How satisfied are youwith the1 23 45support you get fromyourfriends?_ How satisfiedare you with the1 23 4 5conditions of your livingplace?4. How satisfied are you with youri 23 45access to health services?. How satisfiedare you with your1 23 45transport?The following questionrefers to how often you havefelt or experienced certainthings in the last fourweeks.Never Seldom Quiteoften Very often AlwaysHow often do youhave negative4 32 1feelings such as blue mood,despair, anxiety, depression?Do you have anycomments about the assessment?89Appendix B:Physical Activity QuestionnaireName:___________________The following questions ask you about yourinvolvement in physical activity and how you feel aboutyour physical fitness.Please choose the answer that appearsmost appropriate for you.1. Frequencya. Over a typical week howmany times do you engage in aerobic activitythat is sufficientlyprolonged and intense to cause sweatingand a rapid heart beat?o i 2 3 4 56 7b. Over a typical weekhow many times do you engage in strength trainingactivities?o 1 2 34 5 6 72. IntensityWhen you engage in physical activity, whateffort do you think that you make?very light lightmoderate intense very intense1 2 34 53. Perceived FitnessIn a general sense, how would you rate yourcurrent physical fitness?very poor pooraverage good very good1 2 34 5MOTORA LêrDD EJ12TAT12T1$$ L44*.L5 Lc*p øSItit.*at4c—,L_JS47WCN 1XX________AL ALC,040.1 - -C? — — — —Cs-—-—*1 —— L__JDDVII A.1CI SCOI4UGNI TGUH 3COIAIUSCLE GRADINGL tutu pykI pulpable ur kiNu cuAittun2 uuthu mcuum uS. full tunpnojtuvl1y thuhutd3 uutiv amunt. full ruuu of4 uuLhu I toutS. full Ito ofmoth,n. utd t3r.1’ityuttd pr.utduu100ut rufrtono3 thu 11 0I1)iQIS. full toupu ofnutlott. uinut tolty und prcMdotnunnul btot)c3*J-udpurnurtt. RVh$Oft1 to tSnto to 1uucidurud n’tttd ilidujiliuMutnhlblLinll SutMt l0.1NT not tuntablu. Putiont uiutblu kruIi*yuoutt offort or iullubl fur ictt1n IILIOIO lltut.xn noub ut nblUtd,pain ott OflXtSTEPS ZN CLASSIFICATIONTh, tofluud ottki in duuutain thu ubnnthcatiuu.S indiTt&OIO with C.I.emdnt nut luwb. fuu *1 inSt ukttn,uu.nrtob cot riltttnd suRwgiuo. n-l.u.u Sw u tu,. uk oooruS. t.u uk uu.u uo k.I 11l41)Th)00 tItO 011)510 w4oat luwl,fbi in oint ,s&n otO? it fiacc.nt inn..’un. toth d.kn .mdin thu Sw uuuuou00tO intuit I 2I Itmitnu u.buêutr thu tttjuuy in Cutup4ut or tutif nod - 24. ALl) nLi 344 tonu. ‘c’nuno. non? snosaint. o Au. .4.o siu.y .s OSLO! PLtThOthn.’.tu. iqtss) S.ASIA !muSnnottt SotkSSxoiu.To in5tyi tpl&? 4fTSO.PIS..4 ltouuud ZWNO IISbtt..th nntoo.osto01,000 InI054S ifNO, 41344(lIttono tIos .1ltt )ot.btIto notOt10.14 usi t.o, b4t,Appendix C:90Examlnr Name,STA[.IDARD NEUROLOGICAL CLASSIFICAI1ON ISCSOFSPINAL CORD INJURYCuCO07Cs11OWlfootSENSORY001$ W4L2101$A S.va3SWlWcO*10u..tTEONWCtI01PO.Lr0?L_J2OtO 041114).0.PRtSEW1ATIONAItT.1CAUfJjjtou.0.w*.ASIA IMPAIRMENT SCALED 0 CtltLIptOOtu. No tuc4ør or ounootyfunulino 10 pOotrVOd 0011103001011ot5noest{ 2.4.S3.U 10 mploto. fditwny but notfunutinxt to pruntr.od bukow thunuorolcçinal turd s’td toultOtuu LIsaOOII ouniun1o 544$.0 lttu*o3plsou Motor ItinotbO losurntd bukuv Ittu wutóluujuulIuvul. ond nt0.OrOtt03tU lutif of 10evfltfliSl.s bolui dwnouru*4colluvul into u muotkr $1050 bootttun .0.U It InOolpintot Motor ttnstbon to proutrood bokor thonutwobokulluoub, usol us luuot 10015 oSky rntuclot buluorthu nottru.k.51otl krlh&rto ttmu4u.f3or moto.U IL.’ Nnrrn1tMotor and oono000t Auto.tbl ore nomoll.CLINICAL SYNDROMES(OPTIONAL.)U Control CordU Itrown.&uquordU AOLorbrCurslU Cuotuo:4dt5lIutjuU CIOUdO r..nlnttAt’*Ljtl 11*11 of thu1to. ouwelsu. ttskw the.inttli I1))tso40OI Stod rsded 3 or bettor?41500 AlS..l).tM notsrltuettlan Is nurtu4 tin dl tpuututu.4150EA’.o A1$Ehus,.itnfWk...piot.io that no 1 I4uni sinO,,tit4SCIhus J?ino.’tat, tdrid.tb, .4.(i50. are the in ,04n.S 1. o tinuS, ion.’ th..4321 Sno...3.d. us01 on.n -ASIA: Standard neurological classification of spinal cord injuryhttp://www.asia-spinalinjury.org/publications/index.html (accessed 16 Jan 2007).91Appendix D:Modified Borg ScaleSCALE SEVERITYo NoEffortAtAll0.5 Very Very Slight (Just Noticeable)1 Very Slight2 Slight3 Moderate4 Some What Severe5 Severe67 Very Severe89 Very Very Severe (AlmostMaximum)10 Maximum(From: Borg G. A category scale with ratio propertiesfor intermodal and interindividual comparisons.In: GeisslerHG, Petzold P, eds. Psychophysicaljudgement andthe process of perception. Berlin: VEBDeutscher VerlagderWissenschaften, 1982,PP.25—34,)

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Canada 1 0
India 1 0
Germany 1 0
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Ashburn 4 0
Beijing 3 0
Putian 3 0
Plano 2 0
Fuzhou 2 0
Washington 1 0
Phoenix 1 0
Redmond 1 0
Vancouver 1 0

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