Open Collections

UBC Theses and Dissertations

UBC Theses Logo

UBC Theses and Dissertations

The effect of breath-holding during intense intermittent exercise on arterial blood gases, acid-base… Matheson, Gordon Omar 1986

Your browser doesn't seem to have a PDF viewer, please download the PDF to view this item.

Item Metadata

Download

Media
831-UBC_1986_A7_5 M37.pdf [ 5.01MB ]
Metadata
JSON: 831-1.0077288.json
JSON-LD: 831-1.0077288-ld.json
RDF/XML (Pretty): 831-1.0077288-rdf.xml
RDF/JSON: 831-1.0077288-rdf.json
Turtle: 831-1.0077288-turtle.txt
N-Triples: 831-1.0077288-rdf-ntriples.txt
Original Record: 831-1.0077288-source.json
Full Text
831-1.0077288-fulltext.txt
Citation
831-1.0077288.ris

Full Text

The Effect of Breath-Holding During Intense Intermittent Exercise on Arterial Blood Gases, Acid-Base Balance, and Lactate by GORDON OMAR MATHESON M.D. The University of Calgary, 1975 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF PHYSICAL EDUCATION in THE FACULTY OF GRADUATE STUDIES Department of Sport Science School of Physical Education We accept this thesis as conforming to the required standard: THE UNIVERSITY OF BRITISH COLUMBIA June 1986 © Gordon Omar Matheson, 1986 In presenting t h i s thes i s i n p a r t i a l fu l f i lment of the requirements for an advanced degree at the Univer s i ty of B r i t i s h Columbia, I agree that the L ibra ry s h a l l make i t f r ee ly ava i l ab le for reference and study. I further agree that permission for extensive copying of t h i s thes i s for s cho la r ly purposes may be granted by the head of my department or by h i s or her representat ives . I t i s understood that copying or p u b l i c a t i o n of t h i s thes i s for f i n a n c i a l gain s h a l l not be allowed without my wr i t ten permiss ion. Department of The Univer s i ty of B r i t i s h Columbia 1956 Main Mall Vancouver, Canada V6T 1Y3 Date ABSTRACT Eight healthy female volunteers (mean age 24.4 ± 3.4) served as subjects in an experiment measuring acid-base and lactate changes while breath-holding during intense, intermittent exercise. The subjects were endurance trained ( V 0 2 m a x = 56.8 ± 3.9 ml'kg-min"1) with normal resting pulmonary function. Utilizing a counterbalance design, each subject repeated 5 intervals of a 15 second treadmill run at 125 % V 0 2 m a x , once while breath-holding (BH), and once while breathing freely (NBH). Blood samples at rest, at the end of each work and rest interval, and throughout recovery were taken from a teflon catheter inserted in the radial artery. Samples were analyzed for pH, Pa0 2 , PaC0 2 , Sa0 2 , bicarbonate, and lactate. The results were analyzed using repeated measures ANOVA to compare BH with NBH. Significant (p .^01), reductions were found in pH associated with significant elevations in PaC0 2 and HC0 3" at the end of each 15 sec exercise interval in the BH condition. These changes did not persist throughout the rest intervals (p>.05). In addition, significant (p .^01), drops in Pa0 2 and Sa0 2 were found at the end of each exercise interval in the BH condition that were not found at the end of each rest interval. Significantly increased rates of lactate appearance in the arterial blood were found during recovery in the BH conditon. ii It was concluded that breath-holding during intense, intermittent exercise produced acid-base changes greater than those seen at similar exercise intensities while breathing. In addition, breath-holding during intense, intermittent exercise produces significant hypoxia. The significantly increased rates of lactate appearance during recovery in the BH condition are most likely due to increased tissue anaerobiosis. iii TABLE OF CONTENTS Page Abstract ii List of Symbols vi List of Tables vii List of Figures viii Acknowledgements ix Introduction 1 Methods 4 Results 13 Discussion 25 References 33 Appendix A Review of Literature 45 1 Ventilatory and Blood Gas Changes During Exercise 45 1.1 Light to Moderate Exercise 45 1.2 The Lung as a Limiting Factor in Exercise 47 1.3 Maximal Exercise 49 1.4 Ventilatory Costs at Maximal Exercise 51 2 Physiologic Effects of Breath-Holding 54 2.1 BH at Rest 55 2.2 BH During Exercise 60 2.3 The Control of Breath-Holding 62 2.4 Trainability of BH 67 iv 3 Acid-Base Balance During Intense Exercise 67 3.1 Metabolic Acidosis During Exercise 67 3.2 Deleterious Effects of Acidosis 68 3.3 Induced Acidosis and Alkalosis 69 3.4 Extracellular Buffering 71 3.5 Intracellular Buffering 71 4 The Training Stimulus in Intense Exercise 72 4.1 Interval Training 73 4.2 Enhanced Performance During Anaerobic Exercise 74 4.3 Hypoxia and Acidosis as Training Stimuli 75 4.4 BH as an Adjunct in Anaerobic Training 77 B. Treadmill speeds and counterbalance data (Table A1) 78 C. Baseline physiologic data (Table A2) 79 D. Exercise heart rate data (Table A3) 80 E. Individual results (Table A4) 81 F. Lactate values during recovery, n=8 (Table A5) 85 Lactate values during recovery, n=7 (Table A6) 85 v LIST OF SYMBOLS a arterial A alveolar (a-A) arterial-alveolar gradient (A-a) alveolar-arterial gradient ATP adenosine triphosphate 3 tissue buffer capacity BH breath-holding D diffusion capacity ECF extracellular fluid F E V l forced expiratory volume in one second FVC forced vital capacity H+ hydrogen ion HCO3- bicarbonate ion HLa lactic acid NBH non breath-holding PCO 2 partial pressure of carbon dioxide PH negative logarithm of the hydrogen ion concentration PO 2 partial pressure of oxygen RBC red blood cell so2 oxygen saturation TLC total lung capacity V mixed venous V minute ventilation ™2max maximal oxygen consumption vi LIST OF TABLES Page Table 1. Summary of baseline characteristics 13 Table 2. pH, PaC0 2 , Pa0 2 , Sa0 2 , HC0 3" means BH vs NBH after exercise intervals 15 Table 3. ANOVA Results - Exercise Intervals 16 Table 4. pH, PaC0 2 , PaO z, Sa0 2 , HCCy means BH vs NBH after rest intervals 18 Table 5. ANOVA Results - Rest Intervals 19 Table 6. Test for outlier (subject #3) 22 Table 7. ANOVA Results - Recovery Lactate 23 vii LIST OF FIGURES Page Figure 1. Interval exercise protocol 7 Figure 2. Frequency of arterial sampling 10 Figure 3. Rate of lactate appearance from start of exercise to end of recovery BH vs NBH 20 Figure 4. Lactate recovery curve BH vs NBH (n=7) 24 viii ACKNOWLEDGEMENTS This thesis represents the combined efforts of many individuals to whom I am grateful. I sincerely thank the subjects who gave of their time and considerable effort to make this investigation possible and the many enthusiastic volunteers who assisted in the data collection. I extend my sincere appreciation to my committee members: Drs. Doug Clement, Don McKenzie, Bob Schutz, and Howie Wenger for their guidance during all phases of the project. Special thanks is given to Dr. Don McKenzie for his support during the planning phase and to Dr. Bob Schutz for his support and expertise during the data analysis. For their support and encouragement, I dedicate this work to my wife Brenda, and my daughters Kim and Lisa. Finally, I gratefully acknowledge the generous financial assistance of the Alberta Heritage Foundation for Medical Research for making this study possible. ix 1 INTRODUCTION Breath-holding (BH) at rest induces significant changes in acid-base status and blood gas tensions (Hong et al., 1971). BH during exercise appears to accentuate these changes (Astrand, 1960). BH has been the topic of investigations for over 50 years with early research directed towards practical problems such as surviving poisonous gas during World War II (Rodbard, 1947), and oyster and commercial diving safety (Craig and Medd, 1968; Scholander et al., 1962). The voluntary control of BH has been found to be a function of C 0 2 mediated chemical stimuli and non-chemical input related to an elevated central excitatory state (Godfrey and Campbell, 1968). Lin et al. (1974) have further shown that these two stimuli contribute to separate break-points, a 'physiologic break-point' and a 'conventional break-point". Lin et al. (1974), attributed the onset of involuntary ventilation against a closed glottis (physiologic break-point), to chemically mediated stimuli, and the conventional (actual) break-point, to a combination of chemical and central nervous system stimuli. The physiologic effects of BH have been studied at rest (Hong et al., 1971) and during light to moderate exercise (Astrand, 1960) but not during heavy or maximal work. Recently, coaches interested in training their athletes for events which require a large power component to be delivered anaerobically, have been using BH as a possible technique to increase the training stimulus. An 2 increased training stimulus is thought to be achieved by inducing hypoxemia and greater acidosis. However, the usefulness of this training method in improving performance remains to be determined. Hill (1970), used BH during 8 weeks of interval training and found improved anaerobic capacity but the significance of this study is limited since blood parameters were not measured and workloads and BH times were not controlled. Although the specific stimulus which leads to increased power outputs as a result of intense intermittent exercise (interval training) is not known, athletes who train anaerobically demonstrate several adaptations in their ability to buffer H + in the blood and muscle (Parkhouse and McKenzie, 1984). Increased hydrogen ion concentration in the blood and muscle as a result of interval training could be accomplished by increasing the duration or intensity of the work bouts, and/or decreasing the rest interval. Increased C 0 2 resulting from both aerobic and anaerobic metabolism during intense exercise is normally removed in the lungs. BH during exercise, by reducing alveolar C 0 2 ventilation, may reverse the normal C 0 2 / H + equilibrium described by the Henderson-Hasselbach equation and theoretically could increase acidosis at a given workload or produce equivalent acidosis at a lower workload. Mainwood and Cechetto (1980) have demonstrated that the transport of H + and HC0 3" across the muscle cell membrane occurs at a much 3 slower rate than the diffusion of C 0 2 . Therefore, if the equilibrium constant of the equation: C O 2 + H 2 0 ^ * H 2 C O 3 ^ H C O 3 _ + H + favors C 0 2 , intracellular acid-base balance would be maintained. The elimination of C 0 2 from the cell is dependent upon the tissue C 0 2 dissociation curve (Jones, 1980) and the diffusion gradient between the cell and the extracellular fluid (ECF). In turn, the partial pressure of C 0 2 in the ECF is determined by PaC0 2 and PAC0 2 . Thus, changes in the carbon dioxide tension have a direct effect on arterial pH and are controlled by alveolar ventilation. Additionally, BH during intense exercise may produce hypoxemia if oxygen consumption during the period of breath-holding significantly reduces stored oxygen levels. This would indirectly affect acid-base balance (Adams and Welch, 1980). The present study was undertaken in an attempt to quantify the effects of intense, intermittent exercise while BH on arterial gas tensions, acid-base balance, and lactate appearance during recovery. It was hypothesized that BH during exercise would lead to greater increases in PaC0 2 and greater drops in Pa0 2 , Sa0 2 , pH, and bicarbonate. In addition, it was hypothesized that an increased metabolic demand on the muscle cell as a result of BH may be reflected by an increased rate of lactate appearance during recovery. 4 METHODS This study examined arterial blood gases and lactates during and after two treadmill running tests, one performed while breathing freely (NBH) and one while breath-holding (BH). The exercise consisted of five 15 sec intervals at a treadmill velocity calculated to elicit 125% V 0 2 m a x with an additional 5% grade. Eight healthy females served as subjects for both the NBH and BH treatments to allow repeated measures during exercise and recovery. All subjects received informed consent and the experiment received approval from the University of British Columbia, Committee on Experimentation in Humans. Baseline and experimental data were collected between February 24 and March 12,1986. Experimental Design A non-probability sample of 8 subjects was selected from a total of 11 criteria eligible volunteers who had expressed willingness to participate in the study. Criteria for participation included healthy endurance trained females under age 35 with normal pulmonary function. All 11 volunteers met the subject criteria but in two cases injury prevented participation and in one case insertion of the arterial line was unsuccessful. The subjects were healthy, female runners whose weekly training volume did not fluctuate during the period of data collection and for the two months proceeding the 5 study. Although all of the subjects were endurance trained ( V 0 2 m a x > 50 ml-kg"1-min"1), they each participated in varying amounts of interval training. None of the subjects had previous experience with breath-holding during running. Subjects were randomly assigned to one of two order conditions and a counterbalance design was used so that one-half received the BH treatment first and the other half received the NBH first (Table A1). Baseline Data Descriptive physical characteristics and V 0 2 m a x were measured for each subject one week prior to testing. Age, body height (Holtain Ltd.), and weight (Detecto Scales Inc.) were recorded. Pulmonary function at rest was measured using an autospirometer (Minato Medical Science Co. Ltd., model AS-700) and included FVC, % predicted FVC, FEV 1 and % predicted F E V r Immediately following a 5 minute warm-up at 5.0 mph, the subjects performed a continuous horizontal treadmill test (Quintan 24-72 treadmill). The initial treadmill speed was 5.0 m.p.h. and increased by 0.5 m.p.h every minute until fatigue. The test was used to determine maximal oxygen uptake by continuous sampling and analysis of expired gases (Beckman Metabolic Measurement Cart). Respiratory gas exchange variables were tabulated and determined every 15 seconds by a Hewlett Packard 3052 A data acquisition 6 system. V 0 2 m a x was determined by averaging the four highest consecutive 15 second oxygen uptake values. Heart rate was continuously monitored by direct chest lead EKG (Burdick EK/5A electrocardiograph). Exercise Protocol Approximately one hour after completion of the baseline tests, each subject was given an opportunity to practice several BH intervals of the same duration and intensity as the testing protocol. None of the subjects were able to consistently hold their breath for longer than 15 sec while running at the prescribed exercise intensity and therefore, the work intervals were set at 15 sec. In order to place a heavy metabolic load on the exercising muscle, rest intervals were kept short (30 sec), and an additional 5% grade was added to the treadmill. Each subject reported to the laboratory 1 week after baseline testing and approximately 5 hours after their last meal. Following a 4 minute warm-up of treadmill running at a velocity corresponding to 50 % V 0 2 m a x , the treadmill was set at a 5% incline and the speed was adjusted to represent 125% of the subject's V 0 2 m a x (Table A1). The subjects performed 5 repetitions of a 15 sec run in which the workload and work : rest ratio remained constant at 1:2. One-half of the subjects performed the exercise protocol BH first while the other half performed the protocol NBH first. After a one hour rest during which arterial pH and lactate returned to resting values, the subjects repeated the exercise reversing the BH condition. The exercise protocol is outlined in Figure 1. Figure 1 • Interval exercise protocol 125 100 V7, % vo 2max 50 -1 work 4& interval I 1 i i i i i i r i ~~r .5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 time (min) At the start of exercise and during the rest intervals in both BH and NBH, subjects were advised to breathe normally and avoid voluntary hyperventilation. Subjects were allowed to breathe freely during the NBH exercise. Prior to the start of the BH test, subjects were advised to breathe normally, taking one large breath just before starting the treadmill run. Although the subjects were requested not to breathe during 8 the BH protocol and were observed to ensure compliance, no apparatus was used to mechanically prevent or record ventilation. Before the start of exercise and during rest intervals, subjects straddled the moving treadmill. During exercise they entered the treadmill by holding the support bars for 1 to 2 seconds at the start of the interval. On several occasions, subjects experienced some difficulty stepping on the treadmill since the experimental design did not allow for a gradual increase in running speed and the calculated treadmill speeds were high (Table A1). However, with minimal assistance from the experimenters in the first few seconds of the exercise interval, subjects were able to continue without interruption. Although all of the subjects found it extremely difficult to hold their breath for the full 15 seconds, only one subject stepped off the treadmill early in order to breathe. This subject's first treatment condition was BH and her exercise times for intervals one to five were 10 sec, 13 sec, 13 sec, 15 sec, and 10 sec respectively. During her second test (NBH), the same treadmill times were used so that the actual time on the treadmill was equal for both conditions. Another subject was unable to maintain her calculated treadmill speed of 13.75 mph and the treadmill was slowed to 13.5 mph after the 2nd interval in both conditions. 9 Recovery lasted one hour during which subjects were either seated or walking around the laboratory. Data Collection After patency of the ulnar artery at the wrist was ensured in each subject (Allen's test), a teflon coated plastic catheter (22 ga x 2.5 cm Critikon Jelco™ or 20 ga x 4.45 cm Arrow™ with a flexible guidewire) was inserted percutaneously in the right radial artery. A 1% xylocaine hydrochloride solution was used for local anesthesia and sterile technique was followed. The catheters were secured by adhesive tape and the hub was covered by a heparin lock (Argyle Intermittent Infusion Plug). Patency of the catheter was maintained by frequent slow irrigation with a dilute heparin solution (1 cc of 1/100 heparin in 500 cc of 0.9% N Saline). The catheters were inserted prior to the warm-up exercise and were removed immediately following the final blood sample. The average length of time the catheters were in the radial artery was 2 hours. Arterial blood samples were collected anaerobically in 3 cc heparinized plastic syringes by 21 ga needle aspiration directly from the heparin lock of the indwelling catheter. The catheter dead space was not cleared between collections less than 1 min apart since heparin was not injected between these samples and the measured volume of the 10 indwelling catheter and plug was found to be less than 0.05 ml. A total of 19 samples and 45-50 ml of blood were obtained in each test. Blood samples during exercise and recovery were obtained according to the times shown in Figure 2. Figure 2 • Arterial sampling frequency in relation to exercise intervals sample number R1 23 45 67 89 10 11 12 13 14 15 16 17 18 11 y y y y work! interval 1 1 1*—' 1 1 // I 1 // i 1 1 1 1— 0 1 2 3 4 5 7 9 1 4 1 9 24 29 34 time (min) Each sample of 2.5 cc of whole blood was divided equally and 1.25 cc was mixed with sodium fluoride in a test tube (Vacutainer™). This sample was placed in a refrigerated centrifuge (Damon/IEC Division model 2370)) and spun at 800xG for 10 minutes. The supernatant plasma was pipetted off and the sample frozen for later lactate analysis. The remaining 1.25 cc of whole blood was left in the heparinized collection syringe and after ensuring there 11 were no air bubbles in the syringe barrel, the needle of the syringe was stabbed into a solid rubber cork to prevent air leakage. The sample was then buried in ice and analyzed within one-half hour of collection. Laboratory assistants numbered seven: two were stationed on the treadmill as a safety precaution (one also acted as a timer), one collected the arterial samples, two divided the blood samples and centrifuged them, one acted as a courier for blood gas analysis, and the final assistant continuously recorded heart rate. Blood Analysis Pa0 2 , PaC0 2 , and pH were measured using standard silver/silver chloride electrodes with a semi-permeable membrane and a 4 M KCI salt bridge (Corning 175 Automatic pH/Blood Gas System). All blood was analyzed at 37 °C with reference Hb=15 g/dl. Arterial oxygen saturation was calculated from Pa0 2 and pH using a normal standard 0 2 dissociation curve. Bicarbonate concentration was calculated from the Henderson-Hasselbach equation. After thawing the lactate samples, 200 u.l of plasma was vortexed with an equal solution of 0.6N perchloric acid (PCA) and the samples were re-centrifuged for 5 min at room temperature at 11,000xG (Eppendorf centrifuge). 200 jxl of the deproteinized PCA extract was pipetted and diluted with 300 u,l HOH for resting samples and 600 u.l HOH for all other samples. 12 The lactate analysis was performed in duplicate using the technique of enzymatic conversion of lactate to pyruvate in the presence of LDH and NAD, the reliability of this technique being r > .95 (Bergmeyer, 1974). Statistical Analysis The data was treated as a two-factor design with repeated measures on both independent variables; time (18 levels) and breath-holding status (2 levels). Computer analysis of data using analysis of variance (ANOVA) was performed using BMDP statistical software (UCLA, 1981). Respiratory variables (Pa0 2, PaC0 2 , HC0 3", Sa0 2 , and pH) between the two conditions were compared after exercise intervals (R, T1, T3, T5, T7, T9) and after rest intervals (R.T2, T4, T6, T8, T10). Lactate was compared during recovery from T9 to T18. Missing data occurred in only one sample as the result of failed collection. The theoretical value of the missing data point was calculated by comparing the trend in the values before and after the missing point with the mean trend in the remaining 7 subjects. The significance level was not set a priori. 13 RESULTS Baseline Measures Mean values for the measured physiological characteristics are shown in Table 1. Ages ranged from 19 to 29 years. Pulmonary function results were within the range of normal resting values in all subjects. Table 1 • Summary of Physiologic Characteristics (n=8) Mean ± S.D. Age (yrs) 24.4 ± 3.4 Height (cm) 165.3 ± 4.3 Weight (kg) 58.4 ± 4.6 FVC(I) 3.74 ± 0.32 FVC (% predicted) 98.0 ± 8.6 FEV^I) 3.13 ± 0.20 FEV 1 (%predicted) 85.3 ± 6.5 v ° 2 m a x ( m l " k 9 " m i n " 1 ) 56.8 ± 3.9 In all subjects, V 0 2 m a x , which ranged from 50 to 64 ml-kg-min"1, exceeded the usual values observed in untrained, healthy adult females of comparable ages. Four of the subjects were competetive runners with varying amounts of interval training. pH, Pa0 2 , Sa0 2 , PaC0 2 , and Bicarbonate after Work Intervals The arterial blood gases, acid-base status, and lactate levels were within the range of normal resting values in all subjects. Pre-exercise resting values for all variables tested were the same in both conditions at the start of exercise regardless of the order in which the BH condition was administered (Table A4). Subjects reported progressive difficulty holding their breath during the middle 5 sec of the BH exercise interval and experienced the well reported phenomenon of involuntary ventilatory efforts against a closed glottis during the last 5 sec (Agostoni; 1963, Fowler; 1954, Lin et al; 1974). The first respiratory effort after the 15 sec exercise bout (BH) was expiratory in all cases. All subjects reported the workload very demanding, particularly in the BH condition and heart rates after the last exercise bout were near maximal in both conditions (NBH=89.3±3.7% HR m a x , BH=92.1±2.3% HR m a x ) . In addition, significant drop in pH was found in all subjects immediately after completion of the last work bout in both conditions (BH=7.23±.07, NBH=7.29±.06). Since examination of the data revealed apparent differences between BH and NBH in arterial gas tension, bicarbonate and pH at the end of each exercise interval which were not apparent at the end of each rest interval (Table A4), separate analyses were undertaken for work and rest intervals. Points of comparison for repeated measures analyses of variance at the end of each exercise interval included rest (R) and T1, T3, T5, T7, T9 (Figure 2). Table 2 15 Table 2 • Arterial pH, bicarbonate, and blood gas means ± S.D. after exercise intervals. R T1 T3 T5 T7 T9 X T 1 - T 9 NBH 7.43±.03 7.44±.04 7.39±.05 7.36±.05 7.33±.06 7.29±.06 7.36 a. BH 7.44±.02 7.42±.03 7.33±.05 7.29±.06 7.25±.07 7.23±.07 7.30 CM o NBH 36.9±2.2 33.4±2.3 33.5±2.7 31.9±1.6 30.9±2.0 31.1 ±2.4 32.2 u a BH 36.9±3.5 36.8±2.3 42.8±6.8 40.4±7.2 41.3±8.5 37.8±6.4 39.8 •10 o NBH 24.3±1.8 23.0±1.4 20.3±1.6 17.9±1.6 16.3±2.2 15.1 ±2.2 18.5 u X BH 24.6±1.7 24.1 ± 1.2 22.0±2.7 19.4±2.3 18.0±2.4 15.9±2.9 19.9 Q NBH 101 ±6.4 103±14.2 102±7.3 104±9.2 101±8.7 99.4±8.0 102 a BH 99±4.8 84±17.6 75±15.4 78±13 80±14 84.9±13.6 80.4 cs O NBH 97.9±.35 97.8±.71 97.6±.52 97.6±.52 97.4±.74 96.8±.71 97.4 CO CO BH 97.8±.46 95.6±3.3 92.5±4.0 93.1+4.4 92.3±5.5 93.8±4.3 93.5 PC02, P02,mm Hg, HC03~ mequiv-l" Sa02,percent saturation of arterial hemoglobin with O2. BH=breath-holding, NBH=non breath-holding. 16 contains the mean values for all 5 dependent 'respiratory' variables at rest and at the end of each 15 sec exercise interval. The results of the five 2 X 6 (BH status by time) repeated measures ANOVAs are given in Table 3. Table 3 • ANOVA Results - Exercise Intervals ('Respiratory Variables') EXERCISE (R, T1, T3, T5, T7, T9) Variable BH Status Time BHxTime (F,p) (F, P) (F, p) PH 12.7 (<.01) 69.8 (<.001) 6.6 (<.001) PaC0 2 21.0 (<.01) 1.8 (.14) 7.2 (<.001) HC0 3 - 12.1 (.01) 90.6 (<.001) 1.6 (.18) Pa0 2 18.7 (<.01) 4.0 (<.01) 4.8 (.01) S a 0 2 10.9 (.01) 5.0 (<.01) 3.7 (<.01) df 1,7 5,35 5,35 Mean values for arterial pH, Pa0 2 , and Sa0 2 were significantly lower in the BH condition in samples taken immediately after each of the five exercise 17 bouts. Arterial PaC0 2 , and bicarbonate means were significantly elevated immediately after exercise in the BH condition. All five variables displayed marked changes over time. Although the time main effect for PaC0 2 was not significant (p=.14), the highly significant BH X time interaction reflected the the decrease in PaC0 2 for the NBH condition was equivalent to the increased exhibited by the BH condition. Thus, the overall time effect averaged over these two conditions was nonsignificant. pH, Pa0 2 , Sa0 2 , PaC0 2 , and Bicarbonate after Rest Intervals A similar comparison between BH and NBH at the end of each rest interval (immediately before the start of the next work interval) was tested again using repeated measures ANOVAs. Points of comparison included rest (R) and T2, T4, T6, T8, T10 (Figure 2). The mean values for pH, Pa0 2 , Sa0 2 > PaC0 2 and HC0 3 ' (Table 4) were not significantly different between the two conditions when averaged over the end of each rest interval (Table 5), indicating the changes induced by breath holding were corrected during the 30 sec rest interval. Although significant time effects existed for all variables except Pa0 2 , the nonsignificant BH X time interactions indicated that the changes over time were the same for each group. Consequently, these 18 Table 4 • Arterial pH, bicarbonate, and blood gas means ± S.D. after rest intervals. X R 12 T4 T6 T8 T10 T2-T10 NBH 7.43±.03 7.38+.03 7.34±.04 7.31 ±.04 7.28±.06 7.24±.07 7.31 Q. BH 7.44±.02 7.40±.02 7.35+.03 7.31 ±.04 7.27±.05 7.23±.08 7.33 o NBH 36.9±2.2 34.8±3.5 34.5±2.7 33.8±2.6 32.6±2.8 33.8±2.9 33.9 U a BH 36.9±3.5 35.5+2.5 34.4±3.9 34.4±3.3 34.3±3.0 34.0±3.9 34.5 o NBH 24.3±1.8 20.4±2.1 18.5±2.1 17.0±1.8 15.5±2.3 14.4±2.1 17.2 u BH 24.6±1.7 21.6+1.6 18.8±2.2 17.3±2.5 15.9±2.7 14.1 ±3.1 17.5 Q NBH 1 0 U 6 . 4 105+1 1.7 104±1 1.1 101±9.5 99±8.8 105±6.3 103 Q. BH 99±4.8 102±1 1.7 107± 14.1 104±9.8 104±12.5 108±1 1.2 104 O NBH 97.9±.35 97.5±.76 97.4±.74 97.1 ±.83 96.6±.92 96.9±.64 97.1 CO CO BH 97.8±.46 97.6+.52 97.5±.76 97.4±.74 96.9±.83 96.9±.99 97.3 PCO2, P02,mm Hg, HCO3" mequiv-l"' Sa02,percent saturation of arterial hemoglobin with O2. BH=breath holding, NBH=non breath-holding. 19 findings reflect that the changes induced by exercise were the same for both conditions. Table 5 • ANOVA Results - Rest Intervals ('Respiratory Variables') REST (R, T2, T4, T6, T8, T10) Variable BH Status Time BHxTime (F, P) (F, p) (F,p) pH 0.3 (.59) 74.7 (<.001) 1.4 (.25) PaC0 2 0.7 (.43) 5.5 (<.001) 0.5 (.79) HCO3- 0.7 (.42) 106.6 (<.001) 0.8 (.55) Pa0 2 0.7 (.45) 1.5 (.23) 1.3 (.29) S a 0 2 0.7 (.42) 9.3 (<.001) .4 (.87) ~~df Tj 5^ 3! 5^ 3! Lactate During Exercise and Recovery The appearance of lactate in the arterial blood from rest to the end of recovery is shown in Figure 3. Unlike arterial blood gases, pH, and Figure 3 Lactate appearance in arterial blood during exercise and recovery H i I ~ 1  o-( 4—, , , , , , , , r , , , 1 0 6 10 15 20 26 30 36 Time (minutes) 21 bicarbonate, the lactate results did not reveal transient fluctuations attributable to the BH condition and the resultant data points fell along a smooth curve. The rate of appearance of lactate was approximately equal in the two conditions during the exercise protocol (R - T9) however, lactate appeared at a greater rate throughout recovery (T9 - T18) in the BH condition. Evaluating the lactate recovery values for each subject showed consistently greater lactate levels in the BH group with the exception of one subject (#3) who had lactate values during recovery which were markedly increased in the NBH condition (Table A4). The data from this subject also showed variable results in arterial oxygen tension and saturation, but these were not as remarkable. The pH values for subject #3 were lower in the NBH condition during recovery eventhough the PaC0 2 values were elevated after the exercise intervals. However, the PaC0 2 values after the rest interval in the BH condition were also consistently higher indicating less hyperventilation during rest. It was noted that subject #3 required greater manual assistance toward the end of each BH interval and it is conceivable that she may not have worked as hard during the BH condition. Since these results are markedly different from the remaining subjects, and the lactate values from L.H. during recovery were tested to see if they were outlying. To 22 test whether subject #3 was an outlier (lactate values consistently > 2 S.D. from the mean), her lactate values were compared to the mean values of the other 7 subjects during early recovery (Table 6). Subject #3 consistently demonstrated lactate levels which were well below 2 S.D. from the mean in samples taken at T9, T10, T11, T12, and T13. Table 6 • HLa difference (BH-NBH) in Subject #3 H L a B H minus H L a N B H (rnM-l-1) Subject T9 T10 T11 T12 T13 1 +1.9 +4.3 +3.3 +2.4 +2.7 2 +0.8 +0.4 +3.3 +1.7 +3.6 3 -1.3* -5.5* -6.0* -4.5* -4.7* 4 +1.6 -0.3 +1.6 +2.7 +2.8 5 +1.0 +2.5 +3.3 +3.1 +1.5 6 -1.5 +0.2 -0.7 -0.7 -1.2 7 +2.4 +2.3 +1.3 +1.6 +1.3 8 +3.3 +3.6 +2.1 +3.2 +4.9 Mean 1.0 0.9 1.0 1.2 1.4 S.D. ±1.6 ±2.9 ±3.0 ±2.4 ±2.8 -2 S.D. -0.5 -4.9 -4.9 -3.7 -4.3 * Subject #3 is consistently greater than 2 standard deviations beyond the mean values for lactate during early recovery and therefore classified as an outlier. 23 Repeated measures ANOVA comparing lactate means from all 8 subjects (Table A5) during recovery showed they were not significantly different between the two conditions. Both the BH status main effect and the BH X time interaction were nonsignificant, p>.20 (Table 7). Table 7 • ANOVA Results (F, p) - HLa Recovery (T9-T18) n BH Status Time BHxTime (F, P) (F, p) (F, p) 8 2.0 (.20) 238.2 (<.001) 0.6 (.82) df 1,7 9,63 9,63 7* 9.7 (.02) 217.9 (<.001) 2.9 (<.01) df 1,6 9,54 9,54 * reanalysis excluding subject #3 (L.H.) Since subject #3 was classified as an outlier, lactate means during recovery were reanalyzed after dropping her data. The recovery curve (n=7) is plotted in Figure 4. Using this modified analysis of lactate results, significantly elevated levels of lactate were found during recovery in the BH group (Table 7). Figure 4 Lactate appearance in arterial blood during recovery* (n=7) •p-,02 10 16 20 25 30 Time (minutes) DISCUSSION Significant changes were documented in arterial gas tensions, acid-base status, and lactate levels induced by breath-holding during supra-maximal intermittent exercise at sea level in a group of eight fit, endurance trained athletes. These data imply that at similar workloads, breath-holding may produce greater metabolic and respiratory changes than those which occur while breathing normally. The changes which occur in P 0 2 and P C 0 2 tensions during BH are predictable since voluntary apnea with the glottis closed represents a closed system from which 0 2 is continually being removed and C 0 2 added. Changes in PaC0 2 and Pa0 2 parallel changes observed in the alveolus (Hong et al., 1971) and during a single BH, rapid equilibrium is established between mixed venous PC0 2 , alveolar PC0 2 , and arterial P C 0 2 (Clark and Godfrey, 1969). Elevations in the PaC0 2 during BH are thought to result from the combination of several effects (Mithoefer 1964,1959; Lanphier and Rahn, 1963). The large initial inspiration preparatory to breath holding, lowers PAC0 2 and C 0 2 is transferred to the lungs at a rapid rate during the early part of BH thereby rapidly increasing PAC0 2 . As PAC0 2 increases, the transfer of C 0 2 from blood to lungs decreases; the P C 0 2 gradient between the mixed venous and arterial blood falls and disappears within 30 sec of BH. The transfer of 0 2 continues at a much higher rate compared to that of C 0 2 for the duration of BH, resulting in a decreased lung volume. This volume loss concentrates the C 0 2 present in the lung, thereby raising PAC0 2 and PaC0 2 in spite of the fact that the total amount of C 0 2 in the lung increases only slightly. Hong et al. (1971) found that in 4 min of BH at rest, the lung supplied 700 ml of 0 2 to the blood while it gained only 160 ml of C 0 2 back. In addition, uptake of 0 2 by hemoglobin reduces the C 0 2 capacity of the venous blood (Haldane effect) and thus tends to raise PaC0 2 . Both the Haldane effect and the elevation of PAC0 2 by lung volume shrinkage contribute to the fact that the alveolar and arterial P C 0 2 exceed the mixed venous P C 0 2 after 30 sec of BH. Breath-holding during exercise has not previously been reported at workloads above V 0 2 m a x . The majority of investigations have used cycle ergometer exercise at intensities requiring V 0 2 less than 2.0 l-min"1 (Lin et al., 1974; Clark and Godfrey, 1969; Hyde et al., 1968; Lanphier and Rahn, 1963; Craig and Babcock, 1962; Craig etal., 1962; Muxworthy, 1961; Asmussen and Nielsen, 1957). Astrand (1960) used workload increments up to a V 0 2 of 4.2 l-min"1 on a cycle ergometer while breath-holding to study alveolar 0 2 and C 0 2 tensions and Cummings (1962) used moderate intensity treadmill exercise (V0 2 2.6 l-min~1) to study alveolar gases and break-point. BH during exercise produces linear increases in alveolar and arterial PC0 2 and alinear decreases in P 0 2 with the rates of change being proportional to the work intensity (Astrand, 1960; Lanphier and Rahn, 1963; Clark and Godfrey, 1969). Since most of the retained C 0 2 during BH is stored and buffered in the blood and extracellular fluid, changes in pH are inversely proportional to changes in alveolar and arterial P C 0 2 (Hong et al., 1971; Laszlo et al., 1969). At an exercise intensity requiring an oxygen uptake of 2.7 l-min-1 (HR= 140), Astrand (1960) found a PAC0 2 of 65 mm Hg and a PA0 2 of 45 mm Hg at break-point. The BH time at this workload averaged 15 sec. In the present study, 15 sec was chosen for the length of the exercise interval since it was found that most subjects could not BH much longer at intensities above 60 % V 0 2 m a x . In order to produce significant blood gas, pH, and lactate changes in the NBH group during 15 sec of exercise, the rest intervals were kept short and the treadmill speeds were calculated to require 125 % V 0 2 m a x . Significant increases in PaC0 2 are demonstrated during BH (Table 2) with the highest individual value reaching 54 mm Hg. That these changes were induced by BH is shown by the fact they were not present in the NBH condition at the end of the 30 sec work intervals (Table 4). The corresponding elevations in bicarbonate and reductions in pH (Table 2) were transient and reverseable during the rest interval (Table 3), suggesting that they are unlikely to be the result of ion diffusion across the cell membrane (Mainwood and Cechetto, 1980; Robin, 1961). Rather, the observed changes in pH and bicarbonate concentration must result from the relative disequilibrium in the blood bicarbonate buffering system (C0 2 + H 2 0 ^ * H 2 C 0 3 ^ * HC0 3" + H+). Thus breath-holding eliminates the partial ventilatory compensation for the metabolic acidosis seen with exercise intensities above the anaerobic threshold. The significant drops in Pa0 2 and Sa0 2 which were found with BH also appeared to be transient and reverseable during the rest interval. The lowest individual Pa0 2 found during BH was 56 mm Hg while the lowest during NBH was 84 mm Hg. While it has been demonstrated that significant arterial hypoxemia may occur in highly trained athletes exercising at near maximal intensities (Dempsey et al., 1984), inconsistent changes in Pa0 2 tensions were demonstrated in the NBH condition. On the other hand, BH produces marked reductions in Pa0 2 and Sa0 2 in a very short period of time as oxygen 29 stores are depleted. Reductions in Pa0 2 with BH during exercise could result from increased 0 2 uptake, ventilation perfusion uncoupling, or reductions in venous return to the heart. Subject #8 breath-held for only 10 sec in the first exercise interval and yet showed an arterial 0 2 tension of only 60 mm Hg compared to 131 mm Hg while breathing normally. The reductions in Pa0 2 and Sa0 2 during BH may very well be related to reductions in venous return since, although cardiac output at rest during BH at TLC is minimally increased (Lin et al., 1974; Hong et al., 1971), BH accompanied by the valsalva maneuver present in the subjects studied reduces venous return and cardiac output (Paulev, 1969). The subjects in this study reported progressive difficulty maintaining BH toward the end of each 15 sec interval. In the absence of hypoxia, the break-point sensation during BH is thought to occur as a result of the sum or product of C 0 2 mediated (chemical) and non-chemical stimuli (Godfrey and Campbell, 1969; Patrick and Reed, 1969). The non-chemical contribution has been related to the lack of respiratory muscle movement during BH. However the break-point has been demonstrated to be shortened in proportion to exercise intensity (Astrand, 1960) and occurs earlier at a given P C 0 2 during hypoxia (Mithoefer, 1959; Fowler, 1954). Thus, in addition to the elevated PaC0 2 during BH in the present study, the exercise intensity and marked hypoxemia also serve to increase the stimulus to breathe. The subjects did not report increasing difficulty maintaining BH over the five exercise intervals despite significant progressive pH drops since PaC0 2 did not increase over time. The data from subject #3 (L.H.) are inconsistent in several measured variables. In comparison to the other 7 subjects, the pH and Pa0 2 results were reversed in the NBH condition while the bicarbonate and PaC0 2 levels were not. No apparent physiologic explanation can be advanced for this inconsistency and labelling and handling of the sample tubes was done with care. The disparity did not influence significance of the blood gas, pH, and bicarbonate results. When data from this subject showing a reversal in the lactate findings with BH was excluded from the analysis, significant differences in lactate levels were found throughout recovery (Figure 4). Changes in H + and bicarbonate levels in the ECF have been used to study lactate efflux from the muscle cell. Respiratory acidosis (Ehrsam et al., 1982; Graham et al., 1980; Eldridge and Salzer 1967; Engel et al., 1967) and metabolic acidosis (Kowalchuk et al.; 1984, Jones et al., 1977; Steinhagen et al., 1976; Mainwood and Worsley-Brown, 1975) at rest and during exercise are all associated with lower levels of blood lactate. Fujitsuka et al., (1980) 31 found reduced recovery levels of lactate in untrained subjects running to the break-point while BH (21 -26 sec) but peak lactates were only 4-5 mMT 1. In the present study, arterial and hence ECF acidosis was associated with increased lactate levels. Thus, it is unlikely that changes in lactate efflux as a result of pH changes in the ECF could account for the increased lactate levels seen in the BH group. Although the rate of lactate oxidation by heart muscle, skeletal muscle, kidney, and liver was not measured, it is unlikely that it would be different in the two conditions since the induced changes in acid-base balance were transient and not present during rest or recovery. Since pH changes in the muscle are not directly related to changes in the ECF pH (Costill et al., 1984), it is impossible to infer decreases in intracellular pH. However, if intracellular pH did drop as a result of increased C 0 2 diffusion during BH, it may serve to reduce rates of glycolysis and hence lactate levels in the BH group (Sutton et al., 1981). The most likely explanation for the increased lactate levels during recovery phase in the BH condition is increased tissue anaerobiosis (Wasserman, 1984). However, considerable disagreement exists as to the contribution of relative hypoxia to increased energy metabolism via anaerobic glycolysis (Brooks, 1985). Bylund-Fellenius et al., (1984) studied reduced oxygen tensions in the ECF of humans and the hind limbs of rats. They documented increasing lactate levels with decreasing 0 2 tensions during exercise and concluded the relative ECF oxygen tension is important for the intracellular energy and redox state in exercising muscle. Many investigators have reported similar findings (Adams and Welch, 1980; Woodson et al., 1978; Vogel and Gleser, 1972; Hughes.et al., 1968; Piiper et al., 1966). Thus BH, by significantly reducing Pa0 2 , increases the amount of energy produced by anaerobic glycolysis and is reflected in increased lactate levels during recovery. There are interesting implications for these findings. BH during interval training may increase the metabolic energy requirements at a given workload or equal the energy requirements at a reduced workload. Although the, specific training stimulus is not known, greater muscle buffer capacities (Parkhouse et al., 1985) and elevated lactate levels (Poole and Gaesser, 1985) in trained individuals, suggest the hydrogen ion may be the key factor (Adams and Welch, 1980). If this is true, BH during exercise may prove to be an adjunct to training. What remains to be determined is whether the observed changes in arterial blood induced by BH reflect similar changes in muscle pH and lactate. Additionally, a training study is required to establish the presence or absence of benefits associated with BH training. 33 REFERENCES Adams, R.P. and Welch, H.G. Oxygen Uptake, Acid-Base Status, and Performance with Varied Inspired Oxygen Fractions. Journal of Applied Physiology, 49:863-868,1980. Agostoni, E. Diaphragm Activity During Breath Holding: Factors Related to its Onset. Journal of Applied Physiology, 18:30-36,1963. Asmussen, E. and Nielsen, M. Ventilatory Response to C 0 2 During Work at Normal and at Low Oxygen Tensions. Acta Physiologica Scandinavica, 39:27-35,1957. Astrand, P.-O. Breath Holding During and After Muscular Exercise. Journal of Applied Physiology, 15:220-224,1960. Barr, P.-O., Beckman, M., Bjurstedt, H., Brismar, J., Hesser, C M . and Matell, G. Time Courses of Blood Gas Changes Provoked by Light and Moderate Exercise in Man. Acta Physiologica Scandinavica, 60:1-17,1964. Bergmeyer, H.V. Methods of Enzymatic Analysis. Second Edition, Academic Press: New York, 1974. Bjurstedt, H. and Wigertz, O. Dynamics of Arterial Oxygen Tension in Response to Sinusoidal Work Load in Man. Acta Physiologica Scandinavica, 82:236-249,1971. Bradley, M.E. and Leith, D.E. Ventilatory Muscle Training and the Oxygen Cost of Sustained Hyperpnea. Journal of Applied Physiology, 45:885-892,1978. Brooks, G.A. Anaerobic Threshold: Review of the Concept and Directions for Future Research. Medicine and Science in Sports and Exercise, 17:22-31, 1985. Brooks, G.A. and Fahey, T.D. Exercise Physiology. New York: John Wiley and Sons, 1984. Bruce, R.A. Normal Values for V 0 2 and the V0 2 - HR Relationship. American Review of Respiratory Diseases, 129:S41-S43,1984, (supplement). Bryan, A.C., Bentivaglio, L.B., Beerel, F., MacLeish, H., Zidulka, A. and Bates, D.V. Factors Affecting Regional Distribution of Ventilation and Perfusion in the Lung. Journal of Applied Physiology, 19:395-402,1964. Bye, P.T.P., Farkas, G.A. and Roussos, Ch. Respiratory Factors Limiting Exercise. Annual Review of Physiology, 45:439-451,1983. Bylund-Fellenius, A . -C , Idstrom, J.-P., Holm, S. Muscle Respiration during Exercise. American Review of Respiratory Disease, 129:S10-S12,1984, (supplement). Cechetto, D. and Mainwood, G.W. Carbon Dioxide and Acid Base Balance in the Isolated Rat Diaphragm. Pflugers Archiv, 376:251-258,1978. Clark, T.J.H. and Godfrey, S. The Effect of C 0 2 on Ventilation and Breath-Holding During Exercise and While Breathing Through an Added Resistance. Journal of Physiology, 201:551-566,1969. Costill, D.L., Verstappen, F., Kuipers H., Janssen, E. and Fink, W. Acid-Base Balance during Repeated Bouts of Exercise: Influence of HC0 3". International Journal of Sports Medicine, 5:228-231,1984. Craig, A.B. and Babcock, S.A. Alveolar C 0 2 During Breath Holding and Exercise. Journal of Applied Physiology, 17:874-876,1962. Craig, A.B., Halstead, L.S., Schmidt, G.H. and Schnier, B.R. Influences of Exercise and 0 2 on Breath Holding. Journal of Applied Physiology, 17:225-227,1962. Craig, A.B. and Medd, W.L Oxygen Consumption and Carbon Dioxide Production During Breath-Hold Diving. Journal of Applied Physiology, 24:190-202, 1968. Cummings, E.G. Breath Holding at Beginning of Exercise. Journal of Applied Physiology, 17:221-224,1962. Daniels, J. and Scardina, N. Interval Training and Performance. Sports Medicine, 1:327-334,1984. Dannhauer, G. and Ulmer, H.-V. Zur Trainierbarkeit der Atemanhaltezeit -Physiologische und Psychische Aspekte. Leistungssport, 6:29-32,1983. 35 Davis, J.A. Anaerobic Threshold: Review of the Concept and Directions for Future Research. Medicine and Science in Sports and Exercise, 17:6-18, 1985. Dawson, M.J., Gadian, D.C. and Wilkie, D.R. Muscular Fatigue Investigated by Phosphorus Nuclear Magnetic Resonance. Nature, 274:861-866,1978. Dempsey, J.A., Gledhill, N., Reddan, W.G., Forster, H.V., Hanson, P.G. and Claremont, A.D. Pulmonary Adaptation to Exercise: Effects of Exercise Type and Duration, Chronic Hypoxia and Physical Training. Annals of New York Academy of Sciences, 301:243-261,1977. Dempsey, J.A., Vidruk, E.H. and Mastenbrook, S.M. Pulmonary Control Systems in Exercise, Federation Proceedings. 39:1498-1505,1980. Dempsey, J., Hanson, P., Pegelow, D. and Fregosi, R. Mechanical vs. Chemical Determinants of Hyperventilation in Heavy Exercise. Medicine and Science in Sports and Exercise, 14:131,1982a. (abstract). Dempsey, J. , Hanson, P., Pegelow, D., Claremont, A. and Rankin, J. Limitations to Exercise Capacity and Endurance: Pulmonary System. Canadian Journal of Applied Sport Sciences, 7:4-13,1982b. Dempsey, J.A., Hanson, P.G. and Henderson, K.S. Exercise-Induced Arterial Hypoxemia in Healthy Human Subjects at Sea Level. Journal of Physiology, 355:161-175,1984a. Dempsey, J.A., Mitchell, G.S. and Smith, C A . Exercise and Chemorecption. American Review of Respiratory Diseases, 129:S32-S34,1984b, (supplement). Donaldson, S.K.B. and Hermansen, L. Differential, Direct Effects of H +on C a + + - Activated Force of Skinned Fibers From the Soleus, Cardiac and Adductor Magnus Muscles of Rabbits. Pflugers Archiv, 376:55-65,1978. Dudley, G.A., Abraham, W.M. and Terjung, R.J. Influence of Exercise Intensity and Duration on Biochemical Adaptations in Skeletal Muscle. Journal of Applied Physiology, 54:844-850,1982. Edwards, H.Y. Lactic Acid in Rest and Work at High Altitude. American Journal of Physiology, 116:367-375,1936. 36 Ehrsam, R.W., Heigenhauser, G.J.F. and Jones, N.L Effect of Respiratory Acidosis on Metabolism in Exercise. Journal of Applied Physiology, 53:63-69, 1982. Eldridge, F. and Salzer, J. Effect of Respiratory Alkalosis on Blood Lactate and Pyruvate in Humans. Journal of Applied Physiology. 22:461 -468, 1967. Engel, K., Kildeberg, P.A., Fine, B.P. and Winters, R.W. Effects of Acute Respiratory Acidosis on Blood Lactate Concentration. Scandinavian Journal of Clinical and Laboratory Investigation. 20:179-182,1967. Farhi, L.E. Summary: Physiology. American Review of Respiratory Diseases, 129:S3,1984, (supplement). Fowler, W.S. Breaking Point of Breath-Holding, Journal of Applied Physiology. 6:539-545,1954. Fox, E.L., Bartels, R.L., Klinzing, J . and Ragg, K. Metabolic Responses to Interval Training Programs of High and Low Power Output. Medicine and Science in Sports, 9:191-196,1977. Fujitsuka, N., Ohkuwa, T. and Miyamura, M. Blood Lactate After Strenuous Exercise With and Without Breath-holding. Japanese Journal of Physiology, 30:309-312,1980. Gilbert, R. and Auchincloss, J.H. Mechanics of Breathing in Normal Subjects During Brief, Severe Exercise. Journal of Laboratory and Clinical Medicine, 73:439-450,1969. Gledhill, N., Spriet, L.L., Froese, A.B., Wilkes, D.L. and Meyers, E.C. Acid-Base Status with Induced Erythrocythemia and its Influence on Arterial Oxygenation During Heavy Exercise. Medicine and Science in Sports and Exercise, 12:122 (Abstract), 1980. Godfrey, S. and Campbell, E.J.M. The Control of Breath Holding. Respiration Physiology, 5:385-400,1968. Graham, T., Wilson, B.A., Sample, M., Van Dijk, J. and Bonen, A. The Effects of Hypercapnia on the Metabolic Responses to Progressive Exhaustive Work. Medicine and Science in Sports and Exercise, 12:278-284,1980. 37 Grimby, G., Saltin, B. and Wilhelmsen, L. Pulmonary Flow-Volume and Pressure-Volume Relationship During Submaximal and Maximal Exercise in Young Well-Trained Men. Bulletin de Physio-Pathologie Respiratoire, 7:157-168,1971. Halperin, M.L, Karnovsky, M.L and Relman, A.S. On the Mechanism by Which Glycolysis Responds to pH: Implications for Acid-Base Homeostasis. Clinical Research, 15:359,1967. Hanson, J. The Effects of Repetitive Stimulation on the Action Potential and the Twitch of Rat Muscle. Acta Physiologica Scandinavica, 90:387-400, 1973. Harken, A.H. Hydrogen Ion Concentration and Oxygen Uptake in an Isolated Canine Hindlimb. Journal of Applied Physiology, 40:1-5,1976. Harms, S J . and Hickson, R.C. Skeletal Muscle Mitochondria and Myoglobin, Endurance, and Intensity of Training. Journal of Applied Physiology, 54:798-802,1983. Henriksson, J. and Reitman, J.S. Quantitative Measures of Enzyme Activities in Type I and Type II Muscle Fibers of Man After Training. Acta . Physiologica Scandinavica, 97:392-397,1976. Hentsch, U. and Ulmer, H.-V. Trainability of Underwater Breath-Holding Time. International Journal of Sports Medicine, 5:343-347,1984. Hermansen, L. Lactate Production During Exercise. In: Muscle Metabolism During Exercise, editors B. Pernow, B. Saltin, Plenum Press, New York, 1971, pp 401-407. Hermansen, L. and Osnes, J.B. Blood and Muscle pH After Maximal Exercise in Man. Journal of Applied Physiology, 32:304-308,1972. Hill, A.V. The Influence of the External Medium on the Internal pH of Muscle. Proceedings of the Royal Society (London) Serial B, 144:1-22,1955-56. Hill, R.A. An Evaluation of Breath-Holding Technique for Increasing Anaerobic Capacity. (Dissertation for Ph. D., Education), State University of New York, Buffalo, New York, 1970. 38 Hirche, H., Hornbach, V., Langohr, H.D., Wacher, U. and Busse, J. Lactic Acid Permeation Rate in Working Gastrocnemii of Dogs During Metabolic Alkalosis and Acidosis. Pflugers Archiv, 356:209-222,1975. Holmgren, A. and Linderholm, H. Oxygen and Carbon Dioxide Tensions of Arterial Blood During Heavy and Exhaustive Exercise. Acta Physiologica Scandinavica, 44:203-215,1958. Hong, S.K., Moore, T.O., Sato, G., Park, H.K., Hiatt, W.R. and Bernauer, E.M. Lung Volumes and Apneic Bradycardia in Divers. Journal of Applied Physiology, 29:172-176,1970. Hong, S.K., Lin, D.A., Lally, B., Yim, B.J.B., Kominami, N., Hong, P.W. and Moore, T.O. Alveolar Gas Exchanges and Cardiovascular Functions During Breath Holding with Air. Journal of Applied Physiology, 30:540-547,1971. Hughes, R.L., Clode, M., Edwards, R.H.T., Goodwin, T.J. and Jones, N.L. Effect of Inspired 0 2 on Cardiopulmonary and Metabolic Responses to Exercise in Man. Journal of Applied Physiology, 24:336-347,1968. Hultman, E. and Sahlin, K. Acid-Base Balance During Exercise. Exercise and Sport Science Reviews, 8:41 -128,1980. Hyde, R.W., Ricardo, J.M.P., Raub, W.F. and Forster, R.E. Rate of Disappearance of Labeled Carbon Dioxide from the Lungs of Humans During Breath Holding: a Method for Studying the Dynamics of Pulmonary C 0 2 Exchange. Journal of Clinical Investigation, 47:1535-1552,1968. Johnson, R.L., Spicer, W.S., Bishop, J.M. and Forster, R.E. Pulmonary Capillary Blood Volume, Flow and Diffusing Capacity During Exercise. Journal of Applied Physiology, 15:893-902,1960. Jones, N.L. Normal Values for Pulmonary Gas Exchange during Exercise. American Review of Respiratory Diseases, 129:S44-S46,1984, (supplement). Jones, N.L. Hydrogen Ion Balance During Exercise. Clinical Science, 59:85-91, 1980. Jones, N.L., Sutton, J.R., Taylor, R. and Toews, C.J. Effect of pH on Cardiorespiratory and Metabolic Response to Exercise. Journal of Applied 39 Physiology, 43:959-964,1977. Jones, N.L. Exercise Testing in Pulmonary Evaluation: Rationale, Methods, and the Normal Respiratory Response to Exercise. New England Journal of Medicine, 293:541,1975. Karlsson, J., Bonde-Petersen, F., Henriksson, J. and Knuttgen, H.G. Effects of Previous Exercise with Arms or Legs on Metabolism and Performance in Exhaustive Exercise. Journal ofApplied Physiology, 38:763-767,1975. Kita, S., Nagai, I. and Murukami, S. Studies on Fatigue in Frog Sartorius Muscle. Sapporo Medical Journal, 39:144-155,1971. Klausen, K., Knuttgen, H.G. and Forster, H.V. Effect of Pre-existing High Blood Lactate Concentration on Maximal Exercise Performance. Scandinavian Journal of Clinical and Laboratory Investigation, 30:415-419,1972. Knuttgen, H.G., Nordesjo, L-O., Ollander, B. and Saltin, B. Physical Conditioning Through Interval Training with Young Male Adults. Medicine and Science in Sports, 5:220-226,1973. Kowalchuk, J.M., Heigenhauser, G.J.F. and Jones, N.L Effect of pH on Metabolic and Cardiorespiratory Responses During Progressive Exercise. Journal of Applied Physiology, 57:1558-1563,1984. Lanphier, E.H. and Rahn, H. Alveolar Gas Exchange During Breath Holding with Air. Journal ofApplied Physiology, 18:478-482,1963. Laszlo, G., Clark, T.J.H. and Campbell, E.J.M. The Immediate Buffering of Retained Carbon Dioxide in Man. Clinical Science, 37:299-309,1969. Lin, Y.C., Lally, D.A., Moore, T.O. and Hong, S.K. Physiological and Conventional Breath-Hold Breaking Points. Journal of Applied Physiology, 37:291-296, 1974. Linnarsson, D. Dynamics of Pulmonary Gas Exchange and Heart Rate Changes at Start and End of Exercise. Acta Physiologica Scandinavica, 415:1-68, 1974, (supplement). Loke, J. , Mahler, D.A. and Virgulto, J.A. Respiratory Muscle Fatigue After Marathon Running. Journal ofApplied Physiology, 52:821-824,1982. 40 McCartney, N., Heigenhauser, G.J.F. and Jones, N.L. Effects of pH on Maximal Power Output and Fatigue During Short-Term Dynamic Exercise. Journal ofApplied Physiology, 55:225-229,1983. MacDougall, D. and Sale, D. Continuous vs. Interval Training: A review for the Athlete and the Coach. Canadian Journal of Applied Sport Sciences, 6:93-97,1981. Mahler, D.A. and Loke, J. Lung Function After Marathon Running at Warm and Cold Ambient Temperatures. American Review of Respiratory Diseases, 124:154-157, 1981. Mainwood, G.W. and Cechetto, D. The Affect of Bicarbonate Concentration on Fatigue and Recovery in Isolated Rat Diaphragm Muscle. Canadian Journal of Physiology and Pharmacology, 58:624-632,1980. Mainwood, G.W. and Worsley-Brown, P. The Effects of Extracellular pH and Buffer Concentration on the Efflux of Lactate from Frog Sartorius Muscle. Journal of Physiology, 250:1-22,1975. Martin, B., Heintzelman, M. and Chen, H. Exercise Performance After Ventilatory Work. Journal of Applied Physiology, 52:1581-1585,1982. Mithoefer, J.C. Mechanism of Pulmonary Gas Exchange and C 0 2 Transport During Breath Holding. Journal of Applied Physiology, 14:706-710,1959. Mithoefer, J.C. Breath Holding. In: Handbook of Physiology. Respiration. Washington, D.C.: American Physiological Society, 1964, section 3, volume II, chapter 38, pp 1011-1025. Montoye, H.J. An Investigation of Breath-Holding as a Measure of Cardiovascular Fitness. (Ph.D. dissertation Physical Education), University of Illinois, 1949. Moore, R.L. and Gollnick, P.D. Response of Ventilatory Muscles of the Rat to Endurance Training. Pflugers Archiv, 392:268-271,1982. Muxworthy, J.F. Breath Holding Studies: Relationship to Lung Volume. In: Studies in Respiratory Physiology: Chemistry and Mechanics of Pulmonary Ventilation. (A.F. Technical Report No. 6528) Wright-Patterson Air Force Base, Dayton, Ohio, pp 452-473,1961. 41 Olafsson, S. and Hyatt, R.E. Ventilatory Mechanics and Expiratory Flow Limitation During Exercise in Normal Subjects. Journal of Clinical Investigation, 48:564-573,1969. Olsen, C.R., Fanestil, D.D. and Scholander, P.F. Some Effects of Apneic Underwater Diving on Blood Gases, Lactate, and Pressure in Man. Journal of Applied Physiology, 17:938-942,1962. Pannier, J .L , Weyne, J. and Leusen, I. Effects of PC0 2 , Bicarbonate and Lactate on the Isometric Contractions of Isolated Soleus Muscle of the Rat. Pflugers Archiv, 320:120-132,1970. Parkhouse, W.S. and McKenzie, D.C. Possible Contribution of Skeletal Muscle Buffers to Enhanced Anaerobic Performance: a Brief Review. Medicine and Science in Sports and Exercise, 16:328-338,1984. Parkhouse, W.S., McKenzie, D.C, Hochachka, P.W. and Ovalle, W.K. Buffering Capacity of Deproteinized Human Vastus Lateralis Muscle. Journal of Applied Physiology, 58:14-17,1985. Patrick, J.M. and Reed, J.W. The Interaction of Stimuli to Breathing During Breath-Holding. Journal of Physiology, 203:76P-77P, 1969. Paulev, P.-E. Respiratory and Cardiovascular Effects of Breath-Holding. Acta Physiologica Scandinavica, 324:1-116,1969, (supplement). Piiper, J. , Cerretelli, F., Cuttica, F. and Mangili, F. Energy Metabolism and Circulation in Dogs Exercising in Hypoxia. Journal of Applied Physiology, 21:1143-1149,1966. Poole, D.C. and Gaesser, G.A. Response of Ventilatory and Lactate Thresholds to Continuous and Interval Training. Journal of Applied Physiology, 58:1115-1121,1985. Raynaud, J., Martineaud, J.P., Bordachar, J., Tillous, M.C and Durand, J. Oxygen Deficit and Debt in Submaximal Exercise at Sea Level and High Altitude. Journal of Applied Physiology, 37:43-48,1974. Robin, E.D. Of Mice and Mitochondria: Intracellular and Sub-cellular Acid-Base Relationships. New England Journal of Medicine, 265:780-785, 1961. 4 2 Rodbard, S. The Effect of Oxygen, Altitude and Exercise on Breath-Holding Time. American Journal of Physiology, 150:142-148,1947. Roussos, C , Fixley, M., Gross, D. and Mackiem. P.T. Fatigue of Inspiratory Muscles and Their Synergic Behaviour. Journal of Applied Physiology, 46:897-904,1979. Rowell, LB. , Taylor, H.L, Wang, Y. and Carlson, W.S. Sautration of Arterial Blood with Oxygen During Maximal Exercise. Journal of Applied Physiology, 19:284-286,1964. Saltin, B. and Karlsson, J. Muscle Glycogen Utilization During Work of Different Intensities. In: Muscle Metabolism During Exercise, editors Pernow, B., Saltin. B., Plenum Press, New York, 1971, pp 289-299. Scholander, P.F., Hammel, H.T., Le Messurier, H., Hemmingsen, E. and Garey, W. Circulatory Adjustment in Pearl Divers. Journal of Applied Physiology, 17:184-190,1962. Shepherd, R.H. Effect of Pulmonary Diffusing Capacity on Exercise Tolerance. Journal of Applied Physiology, 12-13:487-488,1958. Shephard, R.J. The Oxygen Cost of Breathing During Vigorous Exercise. Quarterly Journal of Experimental Physiology, 51:336-350,1966. Shephard, R.J. The Maximum Sustained Voluntary Ventilation in Exercise. Clinical Science, 32:167-176,1967. Siesjo, B.K. and Messeter, K. Factors Determining Intracellular pH. In: Ion Homeostasis of the Brain, editors B.K. Siesjo, S.C. Sorenson, Academic Press, New York,1971, pp 244-262. Steinhagen, C , Hirche, H.J., Nestle, H.W., Borenkamp, U. and Hosselmann, I. The Interstitial pH of the Working Gastrocnemius Muscle of the Dog. Pflugers Archiv, 367:151-156,1976. Stone, H.L and Liang, I.Y.S. Cardiovascular Response and Control during Exercise. American Review of Respiratory Disease, 129:S13-S16,1984, (supplement). 43 Suskind, M., Bruce, R.A., McDowell, M.E., Yu, P.M.G. and Lovejoy, F.W. Normal Variations in End-Tidal Air and Arterial Blood Carbon Dioxide and Oxygen Tensions During Moderate Exercise. Journal of Applied Physiology, 3:282-290,1950. Sutton, J.R., Jones, N.L and Toews, C J . Effect of pH on Muscle Glycolysis During Exercise. Clinical Science, 61:331-338,1981. Vogel, J.A. and Gleser, M.A. Effect of Carbon Monoxide on Oxygen Transport During Exercise. Journal of Applied Physiology, 32:234-239,1972. Wasserman, K., VanKessel, A.L and Burton G.G. Interaction of Physiological Mechanisms During Exercise. Journal of Applied Physiology, 22:71,1967. Wasserman, K., Whipp, S.N., Koyal, S.N. and Beaver, W.L. Anaerobic Threshold and Respiratory Gas Exchange During Exercise. Journal of Applied Physiology. 35:236-243,1973. Wasserman, K., Whipp, B.J. and Davis, J.A. Respiratory Physiology of Exercise: Metabolism, Gas Exchange, and Ventilatory Control. In: Respiratory Physiology III, volume 23, International Review of Physiology, editor J.G. Widdicombe, University Park Press, Baltimore, 1981, pp:149-211. Wasserman, K. The Anaerobic Threshold Measurement to Evaluate Exercise Performance. American Review of Respiratory Disease, 129:S35-S40, 1984, (supplement). Whipp, B.J., Ward, S.A., and Wasserman, K. Ventilatory Responses to Exercise and Their Control in Man. American Review of Respiratory Disease, 129:S1 -S20,1984, (supplement). Whipp, B.J., Ward, S.A., Lamarra, N., Davis, J.A. and Wasserman, K. Parameters of Ventilatory and Gas Exchange Dynamics During Exercise. Journal of Applied Physiology, 52:1506,1982. Whipp, B.J. The Control of Exercise Hyperpnea. In: The Regulation of Breathing. Dekker, New York, 1981, pp 1069. White, P.D. Observations on Some Tests of Physical Fitness. American Journal of Medical Science. 159:866-874,1920. 4 4 Wilkes, D., Gledhill, N. and Smyth, R. Effect of Acute Induced Metabolic Alkalosis on 800-m Racing Time. Medicine and Science in Sports and Exercise, 4:277-280,1983. Woodson, R.D., Wills, R.E. and Lenfant, C. Effect of Acute and Established Anemia on 0 2 Transport at Rest, Submaximal and Maximal Work. Journal of Applied Physiology, 44:36-43,1978. Young, I.H. and Woolcock, A.J. Changes in Arterial Blood Gas Tensions During Unsteady-State Exercise. Journal of Applied Physiology, 44:93-96,1978. Yudkin, J. and Cohen, R.D. The Contribution of the Kidney to the Removal of a Lactic Acid Load Under Normal and Acidotic Conditions in the Conscious Rat. Clinical Science, 48:121-131,1975. Appendix A 1 Ventilatory and Blood Gas Changes During Exercise A prime function of the respiratory system during exercise is to supply oxygen to the working muscles via the circulatory system. In addition, the pulmonary system provides an important buffering function by increasing the ventilation of C 0 2 which results from the accumulation of lactate when energy requirements of the working muscle are greater than those which can be supplied by the oxidation of pyruvate. In the overall scheme of oxygen transport from the atmosphere to tissues, the process of pulmonary ventilation is not generally considered to be a factor limiting exercise performance at sea level (Bruce, 1984). 1.1 Light to Moderate Exercise The large increase in metabolic rate during exercise is accompanied by corresponding increases in ventilatory output to supply the needs for gas exchange of contracting muscles (Wasserman, et al., 1967). Large increases in minute ventilation (VE), increased respiratory frequency, reduced expiratory fraction of the respiratory cycle, increased peak flow rates, increased capillary blood volume and flow rates, improved distribution of alveolar ventilation, and more uniform distribution of pulmonary blood flow, all occur with exercise (Farhi, 1984). During low intensity exercise, 46 ventilation increases in proportion to the metabolic rate as reflected by the C 0 2 output, and V £ changes as a function of V C 0 2 rather than V 0 2 (Wasserman, 1984; Jones, 1975; Linnarsson, 1974). After a transient drop due to anticipatory hyperpnea at the start of exercise, PaC0 2 (and pH) are stable in steady-state exercise below the anaerobic threshold since V £ and V C 0 2 are closely matched (Whipp et al., 1984). Thus blood gases are maintained near their normal resting levels (Jones, 1984). It is presently assumed that during exercise below the anaerobic threshold, the control of ventilation is mediated through carotid body sensitivity to changes in P C 0 2 (Dempsey et al., 1984; Whipp, 1981). At the start of exercise, before the increased mixed venous P C 0 2 has reached the pulmonary capillary bed, increases in V E are closely related to increases in pulmonary blood flow and the increase in V E is abrupt and step-like. This is correlated to the step-like increase in stroke volume at the start of exercise resulting from increased venous return from the muscle and respiratory pumps (Whipp et al., 1984). When mixed venous P C 0 2 increases, V E also increases but the time required to reach steady state V C 0 2 is 20-30 sec longer than for V 0 2 (Whipp et al., 1982; Linnarsson, 1974). Since V E 47 changes with a time course similar to VC0 2 , the rate of increase in V E at the start of exercise may be slower than V 0 2 and arterial hypoxemia may result. The degree of hypoxemia is usually mild and its duration less than one minute. For example, during the first minute at two intensities of cycle ergometer exercise in which the mean HR reached 115 and 138, Barr-Or et al., (1964) recorded drops in Pa0 2 of 2 and 6 mm Hg. Throughout the remainder of exercise, the Pa0 2 equals resting values or is mildly elevated (Jones, 1984; Barr-Or et al., 1965). 1.2 The Lung as a Limiting Factor in Exercise Limitations in the maximal oxidative rate of energy production in exercising muscle have been attributed to limits in mitochondrial oxidative capacity since mixed venous P 0 2 does not show complete desaturation even with maximal exercise (Brooks, 1985). The lung has long been considered to have sufficient ventilatory reserve to meet the demand for both an increased 0 2 requirement by exercising muscle and an increased C 0 2 removal from venous blood (Bye et al., 1983). Traditionally, the healthy pulmonary system has not been thought to limit exercise in normal subjects and is more than adequate to meet the increased metabolic demands imposed by steady-state exercise at sea level (Dempsey et al., 1980; Wasserman et al., 1981). Several arguments have been advanced to support the assumption that the lung could meet the ventilatory requirements of maximal exercise. Ventilation at V 0 2 m a x is well below maximal voluntary ventilation (Bye et al., 1983), and the capacity to increase ventilation during exercise is much greater than the body's capacity to increase cardiac output or oxygen consumption. For example, at maximum exercise, ventilation can increase approximately 35 times over resting levels whereas cardiac output increases by 5-6 times. Since the slope of the increase in cardiac output during exercise is linear from rest to maximum (Stone and Liang, 1984) whereas the slope of the increase in ventilation is nonlinear (Whipp, 1984), pulmonary minute ventilation to cardiac output or the ventilation : perfusion ratio (VE/Q) may increase 4-5 fold at maximal exercise (Bruce, 1984). Additionally, the ratio of oxygen consumption to ventilation at rest (5 I V E : .251V02) nearly doubles with maximum exercise (190 I V E : 5 I V0 2) and alveolar surface are is approximately 50 m 2 (Brooks and Fahey, 1984). Pulmonary capillary blood volume expands to maximum morphologic limits, topographical distribution of ventilation to perfusion ratios is near uniform, and diffusion capacity of the lung is far in excess of that required to maintain full Hb0 2 saturation of end-pulmonary capillary blood at maximal exercise (Dempsey et al., 1977; Bryan et al., 1964; Johnson et al., 1960; Shepherd, 1958). Thus, the ability to expand ventilation is relatively greater than the ability to expand oxidative metabolism. 1.3 Maximal Exercise At exercise intensities above the anaerobic threshold, the close relationship between V E and V C 0 2 disappears if the duration of work increments is sufficient to allow respiratory buffering of the metabolic acidosis. With increments spaced 4 min apart, V E increases at a faster rate than V C 0 2 whereas with exercise increments of 1 min duration, V E increases at the same rate as V C 0 2 and there is no respiratory compensation for the metabolic acidosis (Wasserman et al., 1967). For exercise bouts longer than one minute, PaC0 2 is driven down to constrain the fall in pH, and V £ rises out of proportion to V 0 2 and V C 0 2 (Wasserman et al., 1984). Although the control of ventilation at exercise intensities associated with significant acidosis is affected by several factors including metabolic acidosis, catecholamines, and body temperature; carotid body [H+] sensitivity appears to be essential in regulating ventilation (Wasserman et al., 1984). Available data has documented the completeness of pulmonary oxygen transport during steady-state exercise up to oxygen consumptions of approximately 3.5 l-min"1. Arterial P 0 2 stays within 5 mm Hg of resting levels (Jones, 1984). Mild hyperthermia and metabolic acidosis cause a rightward shift in the Hb0 2 dissociation curve resulting in a 3 to 5% reduction in Sa0 2 which is usually offset by mild hemoconcentration, resulting in a constant or slightly increased arterial P 0 2 (Dempsey et al., 1982b). However, recent work by Dempsey et al., (1984a, 1984b) documenting significant arterial hypoxemia in short maximal exercise in highly trained male athletes, has questioned the theory that the pulmonary system is capable of meeting ventilatory requirements at maximal exercise. Dempsey, et al., (1984a) found drops in Pa0 2 of 10-40 mm Hg occurring after the first 30 sec of heavy or maximal exercise. These 0 2 tensions remained depressed or fell even lower in samples taken up to 4 min after the onset of exercise. Other investigators have also shown significant drops in arterial P 0 2 during maximal exercise (Gledhill etal., 1980; Rowell et al., 1964; Holmgren and Linderholm, 1958). Young and Woolcock (1978) showed mean drops in Pa0 2 of 33 mm Hg in the first minute of stair climbing in healthy men while PaC0 2 values showed only small variations around resting levels. Significant transient falls in Pa0 2 at the start of exercise or a change in workload have been reported by other investigators (Linnarsson, 1974; Bjurstedt and Wigertz, 1971; Suskind et al., 1950). 51 Theoretical limitations to ventilation during maximal exercise have been proposed to explain the observed arterial hypoxemia. These have included respiratory muscle fatigue, excessive work of breathing, or actual pulmonary failure manifest by an increased (A-a) D0 2 gradient as a result of a ventilation-perfusion inequality, anatomical shunt, or diffusion abnormality (Bye et al., 1983). Dempsey et al., (1984a) observed that the athletes with the worst hypoxemia had the least compensatory hyperventilation during exercise with PaC0 2 values only 1-4 mm Hg below resting levels. He suspected that reduced pulmonary compliance (as a result of increased pulmonary blood volume) prevented the increase in ventilation from rising sufficiently to maintain oxygen tension in the arterial blood and attributed the resultant hypoxemia to a shortened oxygen exchange time as a result of reduced capillary transit time at maximal cardiac output. Interestingly, when Dempsey et al., (1984a) repeated the exercise using a lower density gas instead of air (helium oxygen mixture) alveolar ventilation improved and Pa0 2 increased. Thus it appears that the respiratory system could have corrected the hypoxemia observed with breathing air if ventilation had increased. 1.4 Ventilatory Costs at Maximal Exercise Significant changes in pulmonary mechanics during brief maximal exercise have been reported (Gilbert and Auchincloss, 1969). As opposed to moderate exercise, heavy exercise has tidal flow-volume loops which approach or attain maximum during expiration (Grimby et al., 1971; Olafsson and Hyatt, 1969). Thus, for athletes working at near maximum, a potential mechanical limitation to further increases in expiratory flow (and consequently ventilation) exists. The alternative, an increase in tidal volume, leads to relative hyperinflation, shortening the inspiratory muscles and placing them at a disadvantage. As the elastic work of breathing increases, the efficiency drops and the vulnerability to fatigue increases (Roussos et al.,1979). That the flow-volume curves were near maximal in the study by Dempsey et al. (1984), is shown by the increased ventilation obtained after breathing helium. Inspiratory flow rates at high intensity exercise are also close to the maximum normal values achievable (Grimby et al., 1971; Olafsson and Hyatt, 1969). These flow rates occur at relatively low ventilation, and breathing at higher lung volumes (disadvantageous for inspiratory muscles), does not significantly raise flow rates (Bye et al., 1983). Another reason the subjects in Dempsey's et al. study (1984) may not have increased their ventilation in response to hypoxia may be the increased work of breathing at heavy and maximal exercise. At levels of ventilation above 100 l-min"1, oxygen consumption by the respiratory muscles (V0 2 ), approaches 8 ml 02-l"1 of minute ventilation (Bradley and Leith, 1978; and Shephard, 1966); thus V 0 2 r e s p could exceed 1.0 l-min"1. Bye et al. (1983) calculated that the respiratory muscles during heavy exercise could account for at least 25% of the V 0 2 m a x . Since Bradley and Leith (1978) did not observe any plateau in V 0 2 r e s p during voluntary normocarbic hyperpnea to 200 l-min"1, it is conceivable that at high work loads, oxygen utilization by the ventilatory muscles may be so great that oxygen supply to other tissues is compromised (Bye et al., 1983). Further increases in ventilation then, may be counter-productive. Dempsey et al. (1984) suggested a balance was struck between powerful chemical stimuli at maximal exercise and mechanical 'constraint1 which may limit the usefulness of increased ventilation. The subjects in Dempsey's et al. study (1984) may have failed to increase ventilation to avoid the extra flow-resistive work, and thereby minimize Additionally, ventilation may be limited by fatigue of the respiratory muscles. Shephard (1967) showed that maximum voluntary ventilation is reduced after exercise at 80% of the V 0 2 m a x and this reduction could be prevented with training. In addition, respiratory muscle strength is reduced after exercise (Loke et al., 1982; Mahler and Loke, 1981) and voluntary hyperpnea prior to exercise limits short-term maximal running performance time (Martin et al., 1982). Experiments with rats have shown marked reductions in glycogen content of the respiratory muscles after treadmill running to exhaustion (Moore and Gollnick, 1982). In summary, the balance of information indicates that during mild to moderate exercise in highly trained individuals, or during mild to maximal exercise in untrained individuals, ventilation is sufficient to maintain arterial oxygen saturation and buffer excess C 0 2 . Limitations of ventilation leading to reductions in arterial P 0 2 have been postulated and measured at very heavy and maximal work rates in highly trained athletes. 2 Physiologic Effects of Breath-Holding Breath-holding (BH) is an interesting physiological phenomenon which produces a variety of measureable pulmonary and acid-base changes. Interest in the physiologic effects of BH two to three decades ago led to several investigations but few have appeared since. BH has been used as a measure of physical stamina (Montoye, 1949; Rodbard, 1947) and in one study, it was used to augment anaerobic capacity in interval training (Hill, 1970). Recently, coaches interested in training their athletes for events which require a large power component to be delivered anaerobically, have been 55 using BH as a possible technique to increase the training stimulus. The usefulness of this training method remains to be determined eventhough several BH studies during exercise have been reported. 2.1 BH at Rest The changes which occur in P C 0 2 and P 0 2 in the alveolus and blood with BH at rest are predictable since voluntary apnea results in a closed system. When pulmonary ventilation ceases with the glottis closed, the body becomes a closed system from which 0 2 is continually being removed and to which C 0 2 is continually being added. The main components of this system are the tissues, blood and lungs. When ventilation is blocked, the C 0 2 tension in all tissues must rise proportional to the rate of rise of C 0 2 , the buffering capacity of the blood and tissues, and the rate and distribution of blood flow (Lanphier and Rahn, 1963). Hong et al. (1971) have shown that changes in PaC0 2 and Pa0 2 parallel the observed gas tensions in the alveolus. During a single BH, rapid equilibrium is established between mixed venous PC0 2 , alveolar PC0 2 , and arterial P C 0 2 (Clark and Godfrey, 1969). Investigations measuring the rate of disappearance of inhaled 1 3 C 0 2 during BH have demonstrated an extremely rapid turnover of C 0 2 ; 50% of the inspired isotope disappears within the first 3 sec by rapidly equilibrating with the C 0 2 stored in capillary blood and pulmonary tissues (Hyde et al., 1968). This effect is mediated through the C 0 2 - H + changes described by the Henderson-Hasselbach equation since it is reversed with carbonic anhydrase. Measureable changes reported in the alveolus, arterial blood, and right atrial mixed venous blood in humans with BH at rest include reductions in pH and P0 2 , and an elevation in PC0 2 . After the onset of BH, P C 0 2 shows a steady increase in a linear fashion (Lanphier and Rahn, 1963). Typical values for PAC0 2 at the breaking point of BH are 45-55 mm Hg (Lin et al.,1974; Hong.et al., 1971). The first 2-3 breaths after the termination of BH rapidly restore equilibrium (Clark and Godfrey, 1969). Elevations in the PaC0 2 during BH have been explained by Mithoefer (1964,1959) and Lanphier and Rahn (1963). During BH with air, 0 2 initially represents less than 20% of the lung volume, and as the uptake of 0 2 by tissues progresses, so does the concentration and partial pressure of 0 2 in the lungs. As a result, the 0 2 saturation of arterial blood decreases. However, the transfer of 0 2 from lungs to blood is not significantly affected during the early part of breath holding since alveolar P 0 2 is still relatively high. As the level of P 0 2 drops further, the transfer of 0 2 from the lungs to the blood decreases progressively and results in a smaller arteriovenous 0 2 difference. During the later phases of BH, the tissue demand for oxygen is met by the blood 0 2 stores. The large initial inspiration preparatory to breath holding lowers PAC0 2 markedly and C 0 2 is transferred to the lungs at a rapid rate during the early part of BH, thereby rapidly increasing PAC0 2 . As PAC0 2 increases, the transfer of C 0 2 from the blood to lungs decreases as the result of which the P C 0 2 gradient between the mixed venous and arterial blood falls and disappears within 30 sec of BH. The transfer of 0 2 continues at a much higher rate compared to that of C 0 2 during the rest of BH, resulting in a decrease in lung volume. This volume loss concentrates the C 0 2 present in the lung, thereby raising PAC0 2 and PaC0 2 in spite of the fact that the total amount of C 0 2 in the lung increases only slightly. In fact, Hong et al. (1971) found that in 4 min of BH at rest, the lung supplied 700 ml of 0 2 to the blood while it gained only 160 ml of C 0 2 back. In addition, uptake of 0 2 by hemoglobin reduces the C 0 2 capacity of the venous blood (Haldane effect) and thus tends to raise PaC0 2 . Both the Haldane effect and the elevation of PAC0 2 by lung volume shrinkage contribute to the fact that the alveolar and arterial P C 0 2 exceed the mixed venous P C 0 2 after 30 sec of BH. In addition, the rise in alveolar P C 0 2 reduces the transfer of C 0 2 from tissues into the blood thus suppressing a rise in venous C 0 2 . PaC0 2 equals PvC0 2 after about 30 sec and then exceeds it increasingly so that the (a-A) C 0 2 gradient is reversed during BH (Hong et al., 1971). Consequently, venous pH becomes higher than arterial in the early phase of BH. If PAC0 2 is greater than or equal to PvC0 2 , the main effect is further elevation of the (A-a)PC02 gradient (Lanphier and Rahn, 1963). Therefore, C 0 2 output into the lungs progressively falls and eventually stops during BH, the cycle being reversed and C 0 2 moves from the lungs to the arterial blood (Mithoefer, 1959). In the later stages of BH, the arterial C 0 2 content is observed to increase much more than the arterial 0 2 decreases and the great increase in arterial C 0 2 content is due to an increase in the concentration of reduced hemoglobin (Hong et al., 1971). In 4 min of BH, the lung increases the C 0 2 volume by 231 ml but the tissues produce 680 ml so the blood and tissues must store ~ 450 59 ml. Laszlo et al. (1969) found that most of the C 0 2 retained during rebreathing is stored and buffered in the blood and ECF, and the changes in pH are inversely proportional to the change in PaC0 2 . Other investigators have reported the changes in pH during BH at rest are correlated inversely with increases in P C 0 2 but although significant, the changes are small since the increased concentration of reduced hemoglobin (Haldane effect) carries more H + at a given P C 0 2 (Hong et al., 1971; Mithoefer, 1959). Typical values-for P 0 2 at break-point are 60-65 mm Hg (Lin et al., 1974) although Hong et al. (1971) reported P 0 2 values as low as 30 mm Hg after 4 min of BH. The reduction in P 0 2 at rest is minimal during the first 20 sec of BH and the decline is linear after that (Fowler, 1954; Lanphier and Rahn, 1963; Hon et al., 1971). The alveolar and arterial changes parallel each other and the (A-a) 0 2 gradient remains at about 10 mm Hg throughout the BH period (Hong etal., 1971). Lactate levels increase minimally, showing a steady linear rise after 2 min BH at rest and an even greater rate of rise after the cessation of BH (Hong et al., 1971; Olsen et al., 1962). Cardiac output as measured by the dye-dilution method in subjects BH at rest has been measured 2 min after full inspiration atTLC (Hong etal., 1971). Stroke volume is increased and heart rate reduced with the overall effect being an insignificant increase in cardiac output. Lin et al. (1974), using intraesophageal balloon manometric measurements found that involuntary ventilatory activity during BH generated subatmospheric pressure in the thoracic cavity. He presumed this reduction in intrathoracic pressure was sufficient to promote venous return and increase cardiac output. On the other hand, BH during the valsalva maneuver prevents the rise in cardiac output and stroke volume as a result of increased intrathoracic pressure (Paulev, 1969). 2.2 BH During Exercise During exercise, C 0 2 is produced at a much greater rate. As a result, the maximum time for voluntary apnea is reduced by exercise and associated with a higher P C 0 2 at the termination of BH (Clark and Godfrey, 1969; Astrand, 1960; Muxworthy, 1951). The rate of rise of P C 0 2 is doubled during cycle ergometer exercise at 200 kg-irvmin"1 but the rate of rise remains linear (Clark and Godfrey, 1969). At workloads requiring 0 2 consumption rates of 0.55 to 1.4 l-min"1, Clark and Godfrey (1969) found that increases in the P C 0 2 corresponded to workload increments. Hyde et al. (1968) showed the rate of disappearance of 1 3 C 0 2 to be twice as fast in the first 3 sec of exercise (V0 2 1.25 l-min"1, HR 120). Craig et al. (1962) showed that the rate of rise of P C 0 2 61 with BH during exercise at FI0 2 concentrations from 21 to 100% remained linear and unaffected by elevations in Pa0 2 . During BH at cycle ergometer intensities requiring an oxygen uptake of 0.58 l-min"1, Lanphier and Rahn (1963) found P 0 2 decreased at a much greater rate than at rest. Astrand (1960) used greater workloads performed on a cycle ergometer (0.95 to 4.2 l-min'1, HR 90-190) to show the increase in P C 0 2 and drop in P 0 2 during BH were related to the work intensity. Astrand's subjects held their breath as long as possible while cycling and, at break-point, developed PAC0 2 increases from 54 mm Hg at low exercise intensities to 74 mm Hg at high intensities. PA0 2 showed the opposite changes, dropping from 56 mm Hg to 42 mm Hg at the highest workload, and BH time decreased from 25 to 14 sec as exercise intensity increased. The ventilatory response curve to C 0 2 is affected by exercise and the response line is shifted to the left so that a greater ventilation is achieved at all levels of P C 0 2 (Asmussen and Nielson, 1957). Exercise produces a small but significant decrease in the ventilatory response to C 0 2 (Clark and Godfrey, 1969). The elevation in blood lactate values which occurs during exercise and recovery is blunted in studies which have compared BH or rebreathing to normal ventilation (Fujitsuka et al., 1980; Hong et al., 1971; Engel et al., 1967). Engel et al. (1967) measured the effects of acute hypercapnia upon blood lactate in anesthetized, curarized dogs and found a significant and consistent fall in blood lactate to less than half the control values. In contrast, acute respiratory alkalosis (hypocapnia) produces rapid lactate accumulation (Eldridge and Salzer, 1967). The effect is thought to be a function of the pH dependent glycolytic step in the RBC involving the phosphorylation of fructose-6-phosphate to the diphosphonate by phosphofructokinase (Halperin et al., 1967). Fujitsuka et al. (1980) measured venous lactate values during recovery in 4 subjects and found them to be higher in the NBH group. Scholander et al. (1962) found elevated lactates during recovery following a 1 min dive in Australian divers with the highest lactates at 1-2 min into recovery. Craig and Medd (1968) and Olsen et al. (1962) found increased lactate levels in exercising divers associated with elevations in PAC0 2 and reductions in PAO z. However, in all these studies, pH did not drop below 7.4 and PaC0 2 never rose above 39 mm Hg since divers usually hyperventilate to pH = 7.6 and P a C 0 2 » 17 mm Hg before dives. 2.3 The Control of Breath-Holding The duration of voluntary apnea in the average untrained individual has a large range with reported values between 20 sec (White, 1920) and 270 sec (Hong et al., 1970). It has been assumed that the break-point of BH is related to P C 0 2 since PAC0 2 increases linearly and inspiration of 100% 0 2 provides only a brief prolongation of BH time (Lin et al., 1974). In the absence of hypoxia, the chemical stimulus can be regarded as directly proportional to the chemoreceptor P C 0 2 (Clark and Godfrey, 1969; Godfrey and Campbell, 1968). The breathing stimulus depends on the interrelation of lung volume, hypoxia, and hypercapnia. The relative contributions of chemical stimuli (hypercapnia, acidosis, and hypoxemia) to the break-point of BH has been balanced with the realization that neuromuscular stimuli are also contributory. Fowler (1954) studied subjects BH to break-point and during rebreathing of expired gases (collected in a bag) after break-point. The concentration of C 0 2 in the bag was about 7.5% and the concentration of 0 2 about 8.2%. Eventhough the subject had reached break-point, rebreathing allowed the subject to continue BH two additional times. The PAC0 2 continued to increase and the Pa0 2 to drop through all three BH periods. Fowler concluded that rebreathing served to interrupt the neuromuscular contribution to break-point eventhough the chemical stimulus (pH and blood gas tensions) 64 increased. The effects of hypoxia on break-point are aiinear and difficult to assess (Godfrey and Campbell, 1968). Lin et al. (1974) showed that although BH times were longer after inspiring 100% 0 2 , and the P C 0 2 at break-point was elevated, Pa0 2 at break-point was still > 500 mm Hg at rest and during exercise and thus break-point could not be attributed to hypoxia. Tolerance to hypercapnia and hypoxemia is increased by large lung volumes (Mithoefer, 1959; Fowler, 1954; Muxworthy, 1951) presumably a result of the Hering-Breuer reflex (Godfrey and Campbell, 1968). Hong et al. (1971) showed that P C 0 2 is lower and P 0 2 higher at any point in the BH curve at TLC compared with FRC. Hyperventilation, by lowering PC0 2 , prolongs BH time and hypoxia shortens it (Godfrey and Campbell, 1968). Godfrey and Campbell (1968) hypothesize that the break-point sensation results from the summation of C 0 2 mediated and non-chemically mediated sensations. They suggest the lack of respiratory movement during BH (non-chemical factor) elevates the central excitatory state and hence the urge to resume breathing so that increasing control is required to prevent the contraction of respiratory muscles. Most investigators report an elevated P C 0 2 at the break-point of BH with exercise compared to rest (Lanphier and Rahn, 1963; Craig and Babcock, 1962; Astrand, 1960). The explanation for this observation appears to be that since total BH time is reduced in exercise, chemical factors make up a larger component of the break-point and non-chemical stimuli (absent ventilation) do not have as much time to raise the central excitatory level (Godfrey and Campbell, 1968; Cummings, 1962). Some investigators suggested that the elevated PAC0 2 seen at break-point during exercise, reflected reduced sensitivity to C 0 2 (Astrand, 1960; Muxworthy, 1951). However, Clark and Godfrey (1969) found during moderate cycle exercise while BH or rebreathing, that increasing FIC0 2 did not change the slope of the C O z ventilation response curve and concluded that the ventilatory response to C 0 2 was unaffected by BH at exercise. Not all investigators have reported an elevated PAC0 2 at break-point during exercise (Lin et al., 1974). Craig and Babcock (1962) studied C 0 2 sensitivity after inhaling 100% 0 2 while BH during low-intensity cycle ergometer exercise, and found no change in the P C 0 2 at break-point. Craig et al. (1962) attributed the increased PAC0 2 observed at the break-point during exercise at all levels of inspired oxygen to a systematic sampling error they called 'lag time'. Cummings (1962) used moderate intensity exercise (VQ2 2.6 l-min"1) in which subjects straddled and then jumped on a moving treadmill at speeds up to 9 mph and 6% grade. In subjects running to break-point he found decreased PA0 2 and increased PAC0 2 with increasing work but the differences at break-point were slight. Agostoni (1963) and Fowler (1954) reported that voluntary inhibition of ventilatory muscles becomes impossible as BH progresses while voluntary closure of the glottis is still possible. This finding, together with the tremendous variability in BH times, has been investigated. Lin et al. (1974) used low-intensity cycle exercise (V0 2 0.75 l-min"1) to study respiratory gas changes at the onset of involuntary ventilation against a closed glottis (physiological break-point) and the conventional break-point of BH. They found elevations of PAC0 2 at rest, physiological, and conventional break-points of 39, 46, and 54 mm Hg respectively. Decreases in PA0 2 at the same points were also found (102, 95, and 62 mm Hg). The variability of BH time for a given oxygen consumption was much greater at the conventional break-point than at the physiologic break-point. Exercise at the physiological and conventional break-points produced approximatley equivalent values for both gas tensions. Lin et al. (1974) suggest that the time from the onset of involuntary ventilatory activity to the conventional break-point is mediated by chemical stimuli. They suggest this point is more reliable than the 67 conventional break-point because it is not subject to psychological influences. 2.4 Trainability of BH Dannhauer and Ulmer (1983) have shown that BH time can be trained in a relatively short time. Hentsch and Ulmer (1984) showed that underwater BH time is trainable and that both the time to involuntary ventilation (physiologic break-point) and the time to conventional break-point are increased. 3 Acid-Base Balance During Intense Exercise Complete oxidation in the mitochondria is necessary to fully exploit the energy stored in carbohydrates. When the energy demand exceeds the oxidative capacity of working muscle, or when oxygen supply is limited, the cell must rely on anaerobic sources (Hultman and Sahlin, 1980). Blood lactate levels as high as 32 mlvH"1 have been recorded in continuous, short duration intense exercise (Hermansen, 1971) and in vitro studies have shown a positive correlation between muscle fatigue and the free H + concentration in muscle (Hill, 1955). Thus, regulation of acid-base balance during intense exercise associated with significant acidosis is an important concern. 3.1 Metabolic Acidosis During Exercise Irrespective of the controversy surrounding the concept of the anaerobic threshold and its nomenclature (Brooks, 1985; Davis, 1985), most investigators agree that venous lactate levels reflect the relationship between the rate of lactate production, efflux, and clearance. Lactic acid is a strong organic acid with a pK a < 4 (Mainwood and Worsley-Brown, 1975) and therefore completely dissociates at physiological pH, liberating two molecules of H + for each glucosyl unit metabolized. The dissociation of lactic acid provides the majority of hydrogen ions with the remaining 10% contributed by pyruvate and malate, ATP hydrolysis, the formation of glucose 6-P and glycerol 1-P, and the incomplete oxidation of fatty acids to B-hydroxybutyrate and acetoacetate (Hultman and Sahlin, 1980). Resting pH in the cytosol of muscle is approximately 7.0 with recorded values in humans during intense exercise as low as 6.4 (Hermansen and Osnes, 1972). 3.2 Deleterious Effects of Acidosis The increased intracellular hydrogen ion concentration which results during anaerobic glycolysis produces several deleterious effects on energy metabolism during exercise (Sutton et al., 1981; Hultman and Sahlin, 1980; Hanson, 1973; Kita, 1971). Free protons can alter enzyme conformation by affecting ionizable groups and thereby reduce their substrate binding and catalytic properties. This is particularly true of the rate limiting, non-equilibrium enzymes PFK and HK as well as phosphorylase b, whose activities are reduced in the presence of an increased [H+] (Hultman and Sahlin, 1980). Another effect of intracellular acidosis is to reduce mechanical force generation by the myofibril (Dawson et al., 1978). This is presumably a result of competition between H + and C a + + for binding sites on the troponin molecule and a reduced activity of myofibrillar ATPase, the enzyme responsible for the formation of active cross-bridges between the actin and myosin molecules (Donaldson and Hermansen, 1978). A third effect of intracellular acidosis is to produce alterations in membrane permeability and electrolyte transport (Parkhouse and McKenzie, 1984). These effects combine to reduce the amount of effective work produced by the skeletal muscle cell in the presence of intracellular acidosis, and consequently may impair performance (Karlsson et al., 1975; Klausen et al., 1972). 3.3 Induced Acidosis and Alkalosis The induction of acidosis by oral administration of NH4CI has been associated with reduced muscular performance (Kowalchuk et al., 1984). However, plasma lactate concentrations in the above study were lower with the induced acidosis in exercise. Since the reduced blood pH did not modify the appearance of H + during exercise (similar to control values), it was concluded that the ECF pH influenced lactate appearance in the plasma and that pH is not solely related to the concentration of lactate. Jones et al. (1977) found similar results in submaximal steady-state exercise. Wilkes et al. (1983) induced alkalosis orally and found improved performance, increased levels of lactate, and elevated pH. In addition to lower plasma lactate levels during metabolic acidosis, (Steinhagen et al., 1976; Hirche et al., 1975; Mainwood and Worsley-Brown, 1975) induced respiratory acidosis and alkalosis have been used to study pH and lactate changes at rest (Eldridge and Sa|zer, 1967; Engel et al., 1967) and in working muscle (Graham et al., 1980; Ehrsam et al., 1982). Results similar to those found with induced metabolic acidosis have been reported with induced respiratory acidosis. Postulated mechanisms to explain the reduced lactate appearance during acidosis include the inhibition of muscle anaerobic glycolysis (Sutton et al., 1981), increased lactate metabolism (Yudkin and Cohen, 1975; Hirche et al., 1975), and reduced lactate efflux (Kowalchuk et al., 1984; Sutton et al., 1981; Mainwood and Worsley-Brown, 1975). The pH influence on lactate is H + dependent rather than HC0 3 ' dependent (Mainwood and Worsley-Brown, 1975). Metabolic and respiratory acidosis may influence muscle performance in different ways. Graham et al., (1980) reports a reduced feeling of fatigue in leg muscles of cyclists pedalling to exhaustion while breathing C 0 2 . Steinhagen et al., (1976), report lower muscle performance in metabolic acidosis in isolated muscle preparations while increases in PCQ 2 maintain or 71 even increase performance in isolated muscle preparations (Cechetto and Mainwood, 1978; Pannier et al., 1970). Ehsram et al. (1982) attributed these differences to higher catecholamine levels in hypercapnic acidosis. 3.4 Extracellular Buffering The greatest amount of carbon dioxide (and therefore H+) transport is by the blood-borne bicarbonate buffering system: C 0 2 + H 20^> H 2 C 0 3 ^ HC0 3" + H + (Brooks and Fahey, 1984). Although buffering by this system can take place in the plasma or RBC, the rate of C 0 2 conversion is much greater in the RBC since it contains the enzyme carbonic anhydrase. In the alveolus, the equilibrium of the above equation is reversed where, in the presence of normal ventilation, the PAC0 2 is lower than the PaCO z. 3.5 Intracellular Buffering The buffering capacity of a tissue (B) refers to its ability to resist changes in pH which result from the addition of hydrogen ions. Calculations indicate that during exhaustive exercise, the production of 35 mmolT1 of H + would drop the unbuffered cytosol pH to -1.5 (Hultman and Sahlin, 1980). Intracellular 8 is critical during short duration, high intensity exercise, and there are three known intracellular buffering mechanisms which contribute variable amounts to 8. Physico-chemical buffering occurs through the uptake of protons by weak bases and accounts for 61% of all intracellular buffering (Hultman and Sahlin, 1980). The inorganic phosphates (Pi, ATP, hexose-P, glycerol-P), bicarbonate buffers (COyHCOg"), amino acids, peptides, and proteins comprise this system with the latter group contributing 30% of the physico-chemical buffering. Free histidine, the protein bound histidine residues, and histidine containing dipeptides (carnosine and anserine), are capable of neutralizing large quantities of H + (Parkhouse et al., 1985; Parkhouse and Mckenzie, 1984). The second mechanism of intracellular buffering is the consumption or production of non-volatile acids (the metabolic system) and this contributes 39% of the total B. Metabolic buffers include CP, IMP (inosine-monophosphate), and oxidation of amino acids. Finally, ransmembrane fluxes of H + and HC0 3" ions are also included in the class of metabolic buffers although their contribution is only 1% of the total intracellular buffering. 4 The Training Stimulus in Intense Exercise During progressive incremental exercise continued to exhaustion, the rate of lactate accumulation may become non-linear at a point termed the anaerobic threshold (Brooks 1985; Davis, 1985; Wasserman, 1984). This point is taken to be the V 0 2 at which oxygen delivery mechanisms begin to lag behind the 0 2 demand of exercising muscle (Kowalchuk et al., 1984). However, simply put, anaerobic energy production starts before the capacity for aerobic simply put, anaerobic energy production starts before the capacity for aerobic energy production is fully utilized at all exercise intensities. 4.1 Interval Training Intermittent exercise bouts allow the total training time of high intensity exercise to greatly exceed that of a single bout to exhaustion (MacDougall and Sale, 1981). Interval training has been used as a method of applying intermittent work where the work : rest ratio is controlled in an attempt to influence the proportions of energy supplied by aerobic and anaerobic glycolysis (Daniels and Scardina, 1984). The relative work load at which accumulation of lactate begins is higher in trained subjects (Saltin and Karlsson, 1971). Continuous exercise at 50% and 70% V 0 2 m a x as well as interval exercise at 105% V 0 2 m a x has been shown to increase the lactate threshold equally (Poole and Gaesser, 1985). Animal studies (Dudley et al., 1982; Harms and Hickson, 1983) and human studies (Henriksson and Reitman, 1976) have shown that training continuously at intensities between 50 and 80% V 0 2 m a x is most effective in augmenting the oxidative capacity of type I fibers whereas interval training employing work bouts at intensities greater than or equal to V 0 2 m a x is most effective in augmenting the oxidative capacity of Type II fibers. Fox et al. (1977) showed that interval training reduced lactate accumulation at any given work load and Knuttgen, et al. (1973) demonstrated that this could be accomplished at a variety of work : rest ratios. 4.2 Enhanced Performance during Anaerobic Exercise At the cellular level, one mechanism by which anaerobic training improves performance is thought to be through an increased tolerance to, or removal, of the hydrogen ion. Training which stresses the anaerobic energy delivery system produces adaptations in the mechanisms handling the accumulation of the end products of anaerobic glycolysis. These changes have been reviewed by Parkhouse and McKenzie (1984). It would appear that the small measureable increases in the availabilty of stored energy substrates (ATP and CP) are of such low magnitude that the overall contribution to enhanced anaerobic performance is negligible. Similarly, documented increases in the activity of the glycolytic enzymes are insufficient to significantly improve anaerobic performance. Thus, since anaerobically trained athletes do not appear to have adaptations specifically related to their ATP production capacity, their ability to deal with the inhibitory effects of anaerobic metabolism may be the clue to their improved performance. Although it has not been demonstrated that anaerobic training itself improves 8, greater muscle buffering capacities, better AST performance times, and greater lactate levels have been measured in anaerobically trained athletes (Parkhouse et al., 1985). The finding of significantly increased carnosine levels in the muscle of anaerobically trained athletes and the significant positive correlation between carnosine levels and 8, raises the possibility that anaerobic training can improve tissue buffering capacity by influencing protein synthesis. 4.3 Hypoxia and Acidosis as Training Stimuli Hypoxia is known to occur in working muscle (MacDougall and Sale, 1981). As Davis (1985) points out, femoral vein P 0 2 during exercise is not low enough to indicate whole muscle hypoxia but this does not preclude local hypoxemia. Despite the debate regarding the etiology of lactate accumulation during maximal exercise (Brooks 1985; Davis, 1985), many investigators continue to relate elevated lactate levels to tissue anaerobiosis (Wasserman, 1984). The support for local muscle hypoxia during exercise comes from a variety of reports. Edwards (1936) noted that increased lactate levels in response to standard workloads were greater at higher altitudes. This finding has since been reaffirmed by Raynaud etal. (1974). Vogel and Gleser (1972) used carboxyhemaglobin (COHb) levels of 18-20% to simulate hypobaric hypoxia in the study of oxygen transport during exercise. They found significantly reduced V 0 2 in the COHb group. Although elevated arterial lactate levels were found at the same absolute workload, they were equal in both groups at the same relative workloads (°/<>V02max). Vogel and Gleser (1972) conclude that increased levels of COHb during exercise cause the subject to perform at a higher relative workload. Experiments with dogs at rest and during treadmill running while breathing air and reduced FIQ2 have demonstrated greater lactate levels at similar absolute workloads with increasing hypoxia (Piiper et al., 1966). Again, lactate levels were the same at each relative workload increment (%V0 2 m a x). Hughes et al. (1968) studied subjects exercising on a cycle ergometer to exhaustion while breathing low, normal, and high concentrations of 0 2 . They also demonstrated significant elevations in lactate at the same absolute workloads. Woodson et al. (1978) used acute isovolemic anemia induced by phlebotomy to study oxygen transport during exercise. Significant reductions in hemoglobin (5 gm) were associated with reductions in oxygen carrying capacity of 34%. Pulmonary and radial arterial catheters were inserted to measure changes. Once again, lactate levels were higher at any given workload compared to controls. The relationship between P 0 2 and H + during hypoxic exercise was studied by Adams and Welch (1980). While cycling for 10 min at a steady-state exercise intensity of 55 % V 0 2 m a x and then 90 % V 0 2 m a x to exhaustion, subjects breathed 17, 21, and 60% 0 2 . The hypoxic condition produced greater levels of lactate and H + and reduced levels of P C 0 2 and HC0 3". Adams and Welch (1980) concluded that since improved performance was not found in the hyperoxic condition, the effect of 0 2 levels on performance was mediated by changes in the hydrogen ion concentration. 4.4 Breath-Holding as an Adjunct in Anaerobic Training Only one study has been reported in which BH was investigated as a possible adjunct in anaerobic training. Hill (1970) used BH during 8 weeks of interval training to assess pre and post changes in anaerobic capacity, 440 yard dash performance time, distance of anaerobic run, and finger-prick lactate levels (n=28 males). The specific training schedule and BH techniques were not outlined but it appeared that the treatment group breath-held until the break-point 3 times per week while interval sprinting. After 8 weeks, Hill found the distance of the anaerobic run was significantly longer, the anaerobic capacity greater, and the distance of the treadmill run at V 0 2 m a x was longer. There were no significant changes in lactate or 440 yd dash times although a positive trend existed. Appendix B Table A1 • Counterbalance Data and Treadmill Speeds Trial Order V 0 2 m a x Treadmill Experimental Treadmill BH NBH Speed (mph) Speed* (mph) S.L. 1 2 10 12.5 L S . 2 1 11 13.75 L.H. 2 1 9.5 11.9 L.F. 1 2 9.25 11.56 S.M. 2 1 9.25 11.56 C.H. 1 2 10 12.5 L.D. 2 1 11 13.75 M.N. 1 2 11 13.75 * Exercise intervals were performed at a treadmill speed corresponding to 125% V 0 2 m a x with an additional 5% grade. Appendix C Table A2 • Subject Physiologic Data 79 AGE HEIGHT WEIGHT FVC FVC FEV. (yrs) (cm) (kg) F E V 1 V 02max (I) (%pred) (I) (%pred) (ml-kg-min"1) S.L. 29 166.5 67.0 3.98 107 3.18 81 49.27 L S . 27 168.3 60.9 3.98 102 3.21 81 55.99 L.H. 24 159.8 53.0 3.37 89 2.98 97 54.44 L.F. 28 169.1 63.0 3.63 92 2.86 79 55.45 S.M. 24 159.7 57.5 3.83 110 3.42 89 59.67 C.H. 20 160.7 55.1 3.12 85 2.87 92 56.85 L.D. 19 170.9 56.8 3.91 94 3.37 86 59.04 M.N. 24 167.7 53.8 4.07 105 3.12 77 63.35 80 Appendix D Table A3 • Heart Rate Data Max HR (b-mirf1) HR after Interval #5 (b-mirr1) (recorded during determination NBH BH of V02 m a x) actual %max actual %max S.L. 185 170 91.9 175 94.6 L.S. 200 175 87.5 182 91.0 L.H. 190 180 94.7 180 94.7 L.F. 200 172 86.0 182 91.0 S.M. 175 160 91.4 160 91.4 C.H. 190 170 89.5 L.D. 190 170 89.5 180 94.7 M.N. 190 160 84.2 170 89.5 Mean±S.D. 89.3±3.7 92.1±2.3 Appendix E Table A4 • Sub jec t Data 81 Subject *1 S.L. R 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 PH NBH 7.43 7.50 7.41 7.41 7.38 7.38 7.33 7.36 7.30 7.32 7.29 7.29 7.30 7.30 7.36 7.38 7.42 7.40 7.43 BH 7.45 7.44 7.39 7.38 7.37 7.34 7.34 7.31 7.29 7.29 7.25 7.26 7.25 7.25 7.32 7.35 7.38 7.40 7.41 p C 0 2 mmHg NBH 38 31 30 32 33 30 32 28 30 28 29 30 28 31 30 33 32 37 36 BH 36 35 33 33 28 32 30 30 30 29 28 28 28 29 30 32 33 34 34 HC0 3" meq /1 NBH 25 24 19 20 19 18 17 16 14 14 14 14 14 15 17 20 21 23 24 BH 25 24 20 19 16 18 16 15 14 14 12 12 12 13 15 18 19 21 22 p 0 2 mmHg NBH 99 108 114 106 108 101 106 102 105 101 103 115 119 115 111 101 109 92 92 BH 101 86 105 100 120 95 107 97 105 101 119 116 118 116 108 100 99 89 96 S a 0 2 %age NBH 98 98 98 98 98 98 98 98 97 97 97 98 98 98 98 98 98 97 97 BH 98 97 98 98 98 97 98 97 97 97 98 98 98 98 98 97 97 97 97 HLa mM / 1 NBH 0.7 1.3 3.7 6.8 8.9 9.4 10.7 11.3 12.3 10.4 9.9 9.3 8.8 8.9 6.8 4.5 3.5 2.6 1.8 BH 0.9 2.3 4.5 6.2 6.4 9.1 9.5 10.1 11.4 12.3 14.2 12.6 11.2 11.6 11.1 8.3 6.8 5.2 3.9 R 1 2 3 4 5 Subject• 6 7 8 *2 9 L.S 10 11 12 13 14 15 16 17 18 PH NBH 7.43 7.41 7.34 7.29 7.27 7.23 7.21 7.16 7.17 7.10 7.08 7.10 7.08 7.15 7.20 7.26 7.31 7.33 BH 7.42 7.38 7.37 7.29 7.30 7.24 7.23 7.16 7.17 7.13 7.09 7.10 7.06 7.07 7.12 7.16 7.23 7.29 7.30 p C 0 2 mmHg NBH 38 37 33 39 31 36 30 30 29 33 32 27 27 24 26 27 27 33 BH 36 39 33 40 34 38 29 41 31 31 31 30 31 27 24 28 28 26 32 HCO; meq /1 NBH 25 23 18 18 14 15 12 11 11 10 9 8 8 8 10 12 14 18 BH 23 23 19 19 16 16 12 15 11 10 9 9 9 8 8 10 12 13 16 p 0 2 mmHg NBH 97 93 120 99 101 93 102 102 99 107 110 119 118 120 115 116 111 92 BH 101 58 125 65 121 75 117 75 108 100 111 114 114 115 120 113 109 114 100 S a 0 2 %age NBH 98 97 98 97 97 96 97 96 96 96 96 97 97 97 97 98 98 97 BH 98 90 98 90 98 93 98 91 97 96 96 97 96 96 97 97 97 98 97 HLa mM / 1 NBH 0.7 4.0 7.6 9.9 11.7 13.8 13.5 14.7 15.8 14.4 14.9 13.1 12.4 11.8 9.7 8.4 7.3 BH 0.7 2.3 4.6 6.9 8.5 9.0 9.7 12.7 14.1 15.5 16.2 17.7 16.6 16.7 13.6 12.0 9.2 9.1 7.8 Table A4 continued • Sub jec t Data 82 Subject *3 L.H. R 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 pH NBH 7.45 7.44 7.39 7.42 7.35 7.40 7.35 7.38 7.34 7.33 7.26 7.26 7.25 7.28 7.32 7.42 7.38 7.40 7.40 BH 7.43 7.45 7.40 7.41 7.38 7.38 7.36 7.37 7.34 7.36 7.35 7.33 7.33 7.35 7.42 7.40 7.40 7.43 7.40 p C 0 2 mmHg NBH 37 35 32 3 2 35 30 33 3 0 30 31 33 3 2 32 31 34 29 36 36 39 BH 4 0 36 36 37 36 3 5 36 34 37 34 35 3 5 37 38 3 3 3 9 41 38 40 H C O ; meq/1 NBH 2 6 2 3 19 21 19 18 19 18 17 16 15 14 14 14 18 19 21 22 24 BH 26 2 5 2 2 2 3 21 2 0 20 20 20 19 19 19 20 21 21 24 25 25 25 p 0 2 mmHg NBH 96 91 106 94 91 93 91 87 87 87 98 109 105 107 98 111 91 100 99 BH 92 94 91 94 93 87 97 92 95 89 101 107 109 100 99 99 97 103 96 S a 0 2 %age NBH 98 97 98 97 97 97 97 97 96 96 97 97 97 97 97 98 97 98 98 BH 97 98 97 97 97 97 97 97 97 97 97 98 98 97 98 98 97 98 97 HLa mM/1 NBH 0.7 2.4 3.6 5.2 6.4 7.4 7.4 8.5 9.3 12.1 12.9 13.7 11.7 10.9 9.2 5.4 3.8 3.5 2.7 BH 0.6 3.4 5.5 6.0 7.0 7.9 8.5 9.1 9.1 10.8 7.4 7.7 7.2 6.2 5.3 4.1 2.4 2.4 2.6 R 1 2 3 4 5 Subject *4 L.F 6 7 8 9 10 11 12 13 14 15 16 17 18 PH NBH 7.38 7.40 7.35 7.36 7.31 7.31 7.27 7.27 7.24 7.25 7.19 7.17 7.20 7.20 7.22 7.24 7.27 7.26 7.30 BH 7.41 7.42 7.38 7.33 7.33 7.29 7.28 7.25 7.24 7.20 7.17 7.18 7.18 7.18 7.23 7.27 7.31 7.32 7.34 p C 0 2 mmHg NBH 3 6 3 2 3 5 31 34 31 31 31 33 2 9 3 5 34 2 9 3 0 31 34 3 3 36 34 BH 3 7 34 3 7 38 36 35 37 36 36 38 37 33 31 30 32 31 32 33 32 HC0 3" meq/1 NBH 21 20 19 18 17 16 14 14 14 13 13 12 11 12 13 15 15 16 17 BH 23 22 2 2 2 0 19 17 17 16 15 15 13 12 11 11 13 14 16 17 17 p o 2 mmHg NBH 103 109 111 111 109 112 112 108 108 109 113 117 118 116 114 103 104 9 9 101 BH 102 96 102 80 106 78 100 91 106 84 111 121 121 118 115 110 110 107 109 S a 0 2 %age NBH 98 98 98 98 98 98 98 97 97 97 97 97 98 97 97 97 97 97 97 BH 98 98 98 95 98 94 97 96 97 94 97 98 98 97 98 98 98 98 98 HLa mM/1 NBH 1.5 2.8 4.1 5.4 6.3 7.3 7.8 9.5 9.9 10.9 11.9 10.7 10.0 9.1 6.5 5.4 5.5 4.6 3.7 BH 1.1 2.5 3.5 6.2 7.3 7.0 9.1 10.1 11.3 12.5 11.6 12.3 12.7 11.9 10.5 7.6 8.1 6.2 3.8 Table A4 continued • Sub jec t Data 83 Subject *5 S.M. R 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 PH NBH 7.42 7.43 7.40 7.42 7.37 7.39 7.34 7.37 7.32 7.34 7.30 7.30 7.30 7.29 7.33 7.37 7.41 7.39 7.41 BH 7.42 7.46 7.44 7.31 7.37 7.34 7.34 7.29 7.30 7.24 7.25 7.26 7.23 7.25 7.29 7.31 7.34 7.37 7.37 p C 0 2 mmHg NBH 38 36 36 34 37 32 35 32 34 32 31 33 32 34 36 35 32 37 38 BH 43 35 35 50 37 39 34 37 34 40 35 32 33 32 34 35 34 37 38 HC0 3" meq/1 NBH 25 24 22 22 21 20 19 18 17 17 15 16 16 16 19 20 20 22 24 BH 28 25 24 25 21 21 18 18 17 17 15 14 14 14 16 18 18 21 22 p 0 2 mmHg NBH 97 90 92 102 96 105 101 104 99 101 110 114 111 108 101 99 106 88 92 BH 92 97 102 60 105 94 109 87 127 83 120 134 127 123 116 1 17 116 126 103 S a 0 2 %age NBH 98 97 97 98 97 98 97 98 97 97 98 98 98 98 97 97 98 97 97 BH 97 98 98 88 98 97 98 96 98 94 98 98 98 98 98 98 98 98 98 HLa mM/1 NBH 0.7 1.1 3.2 6.6 7.7 8.9 9.1 9.3 9.8 10.3 11.5 9.4 9.1 8.8 7.0 5.2 3.7 2.8 2.4 BH 1.5 1.7 3.6 4.3 6.9 7.8 10.6 11.1 11.7 11.3 14.0 12.7 12.2 10.3 10.1 8.1 6.8 3.8 1.9 R 1 2 3 4 5 Subject *6 6 7 8 9 C.H 10 11 12 13 14 15 16 17 18 PH NBH 7.44 7.46 7.36 7.42 7.34 7.37 7;31 7.33 7.28 7.28 7.22 7.22 7.24 7.26 7.29 7.32 7.36 7.38 7.40 BH 7.44 7.45 7.37 7.31 7.34 7.23 7.31 7.21 7.28 7.28 7.25 7.21 7.24 7.27 7.31 7.33 7.37 7.39 7.39 p C 0 2 mmHg NBH 39 33 41 35 37 34 36 34 36 35 38 34 31 29 31 32 33 34 35 BH 36 37 40 51 40 52 38 50 38 38 38 36 33 33 34 36 35 35 36 H C O ; meq/1 NBH 26 24 24 22 20 19 18 18 17 16 15 14 13 13 15 17 19 20 22 BH 24 26 23 26 21 22 19 20 18 18 17 14 14 15 17 19 20 21 22 p 0 2 mmHg NBH 106 111 98 108 120 117 105 108 104 103 108 119 119 120 110 109 102 102 100 BH 104 100 94 69 100 70 113 71 105 87 1 11 115 112 119 113 103 114 103 96 S a 0 2 %age NBH 98 97 97 98 97 98 97 98 97 97 98 98 98 98 97 97 98 97 97 BH 97 98 98 88 98 97 98 96 98 94 98 98 98 98 98 98 98 98 98 HLa mM/1 NBH 0.7 0.9 3.5 5.0 6.8 8.7 9.3 10.7 11.5 12.8 12.7 13.0 11.9 11.1 9.9 8.1 7.2 5.7 5.3 BH 0.5 1.1 3.4 4.1 6.1 7.5 8.5 10.5 10.7 11.3 12.9 12.3 11.2 9.9 8.3 7.0 5.7 4.6 3.9 Table A4 continued • Sub jec t Data 84 Subject *7 L.D. R 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 PH NBH 7.41 7.45 7.34 7.37 7.31 7.34 7.29 7.32 7.27 7.31 7.25 7.25 7.31 7.31 7.36 7.39 7.40 7.41 7.42 BH 7.44 7.37 7.40 7.29 7.37 7.24 7.32 7.19 7.28 7.19 7.21 7.25 7.26 7.27 7.36 7.36 7.39 7.39 7.40 p C 0 2 mmHg NBH 37 3 2 3 8 34 38 3 3 37 3 3 37 33 36 37 31 3 5 34 3 5 37 37 35 BH 36 41 3 7 4 9 34 50 3 7 54 36 48 38 34 3 3 37 33 36 36 36 37 H C O ; meq/1 NBH 2 3 2 2 20 20 19 18 17 17 17 17 16 16 15 18 19 21 23 23 23 BH 24 24 22 23 19 22 19 21 17 18 15 15 15 17 19 21 22 22 23 p 0 2 mmHg NBH 96 94 86 90 89 90 86 87 84 88 94 99 113 102 102 101 98 100 105 BH 9 7 74 88 58 86 5 7 86 5 6 83 58 85 99 105 102 102 98 100 92 90 S a 0 2 %age NBH 9 7 98 96 97 96 97 96 96 95 96 96 97 98 97 98 98 97 98 98 B H 9 8 9 5 97 87 9 6 84 96 81 9 5 84 9 5 97 97 97 98 97 98 97 97 HLa mM/1 NBH 0.5 0.6 3.5 4.4 5.8 6.3 6.7 6.5 6.8 7.2 7.7 6.8 5.8 5.2 3.9 2.7 2.2 1.7 1.1 BH 0.7 0.9 3.0 2.6 5.3 6.1 6.0 8.6 9.3 9.6 10.0 8.1 7.4 6.5 5.2 3.7 3.0 2.1 1.8 R 1 2 3 4 5 Subject 6 7 8 *8 9 M.N. 10 11 12 13 14 15 16 17 18 PH N B H 7.47 7.49 7.42 7.44 7.40 7.40 7.36 7.38 7.34 7.34 7.29 7.32 7.33 7.35 7.38 7.40 7.42 7.44 7.44 BH 7.48 7.42 7.41 7.29 7.35 7.26 7.32 7.20 7.28 7.18 7.26 7.27 7.24 7.26 7.30 7.33 7.38 7.42 7.43 p C 0 2 mmHg NBH 3 2 31 3 3 31 31 31 30 2 9 31 3 2 35 31 32 31 33 34 34 34 3 4 BH 31 3 7 3 3 44 30 4 2 34 48 3 2 44 30 28 2 9 28 3 2 3 5 3 3 31 32 H C O ; meq/1 NBH 2 3 24 22 21 19 19 17 17 17 17 17 16 17 17 2 0 21 22 23 23 BH 24 24 21 21 17 19 17 19 15 16 13 13 13 13 16 18 19 20 21 p 0 2 mmHg N B H 114 131 111 107 114 110 110 106 103 107 104 107 111 106 105 100 96 104 103 BH 103 60 108 73 125 71 102 67 100 77 106 120 110 112 110 99 109 114 111 S a 0 2 %age NBH 98 99 98 98 98 98 98 98 98 98 97 98 98 98 98 98 98 98 98 BH 98 91 98 93 98 92 97 89 97 92 97 98 97 98 98 97 98 98 98 HLa mM/1 N B H 0.3 0.7 3.8 4.4 5.7 6.2 7.4 8.1 9.7 9.1 9.0 9.6 7.2 5 .0 4.8 3.4 3.0 2.3 1.9 BH 0.4 1.0 4.0 4.8 7.6 7.9 8.5 9.6 10.9 12.4 12.6 11.7 10.4 9.9 8 .4 5.8 5.4 4.2 2.8 Appendix F Table A5 • Lactate mean values ± S.D. during recovery* Analysis by repeated measures ANOVA (n=8). 10 11 12 13 14 15 16 17 18 NBH 10.9 11.4 10.9 9.9 9.0 7.6 5.8 4.8 4.0 3.3 ±2.3 ±2.5 ±2.6 ±2.9 ±2.8 ±2.8 ±2.9 ±2.5 ±2.2 ±2.1 BH 12.0 12.4 11.9 11.1 10.4 9.1 7.1 5.9 4.7 3.6 ±1.7 ±2.7 ±3.1 ±3.0 ±3.3 ±3.9 ±2.6 ±2.3 ±2.2 ±1.9 * ps.1958 for main effect BH Status. Lactate mM-l .1-1 Table A6 • Lactate mean values ± S.D. during recovery excluding subject #3*. Analysis by repeated measures ANOVA (n=7) 10 11 12 13 14 15 16 17 18 NBH 10.8 11.2 10.5 9.7 8.7 7.3 5.9 5.0 4.0 3.4 ±2.4 ±2.7 ±2.5 ±3.0 ±2.9 ±2.9 ±3.1 ±2.7 ±2.4 ±2.2 BH 12.1 13.1 12.5 11.7 11.0 9.6 7.5 6.4 5.0 3.7 ±1.8 ±2.0 ±2.8 ±2.8 ±3.1 ±2.6 ±2.5 ±2.0 ±2.2 ±2.0 *p=.02O7 for main effect BH Status. Lactate mM-l*1. 

Cite

Citation Scheme:

        

Citations by CSL (citeproc-js)

Usage Statistics

Share

Embed

Customize your widget with the following options, then copy and paste the code below into the HTML of your page to embed this item in your website.
                        
                            <div id="ubcOpenCollectionsWidgetDisplay">
                            <script id="ubcOpenCollectionsWidget"
                            src="{[{embed.src}]}"
                            data-item="{[{embed.item}]}"
                            data-collection="{[{embed.collection}]}"
                            data-metadata="{[{embed.showMetadata}]}"
                            data-width="{[{embed.width}]}"
                            async >
                            </script>
                            </div>
                        
                    
IIIF logo Our image viewer uses the IIIF 2.0 standard. To load this item in other compatible viewers, use this url:
https://iiif.library.ubc.ca/presentation/dsp.831.1-0077288/manifest

Comment

Related Items