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T J Barstow

Publications and source records attributed to T J Barstow.

At least 37 records · Page 2Linked to original sources

VO2 kinetics in the horse during moderate and heavy exercise.

The horse is a superb athlete, achieving a maximal O2 uptake (approximately 160 ml . min-1 . kg-1) approaching twice that of the fittest humans. Although equine O2 uptake (VO2) kinetics are reportedly fast, they have not been precisely characterized, nor has their exercise intensity dependence been elucidated. To address these issues, adult male horses underwent incremental treadmill testing to determine their lactate threshold (Tlac) and peak VO2 (VO2 peak), and kinetic features of their VO2 response to "square-wave" work forcings were resolved using exercise transitions from 3 m/s to a below-Tlac speed of 7 m/s or an above-Tlac speed of 12.3 +/- 0.7 m/s (i.e., between Tlac and VO2 peak) sustained for 6 min. VO2 and CO2 output were measured using an open-flow system: pulmonary artery temperature was monitored, and mixed venous blood was sampled for plasma lactate. VO2 kinetics at work levels below Tlac were well fit by a two-phase exponential model, with a phase 2 time constant (tau1 = 10.0 +/- 0.9 s) that followed a time delay (TD1 = 18.9 +/- 1.9 s). TD1 was similar to that found in humans performing leg cycling exercise, but the time constant was substantially faster. For speeds above Tlac, TD1 was unchanged (20.3 +/- 1.2 s); however, the phase 2 time constant was significantly slower (tau1 = 20.7 +/- 3.4 s, P < 0.05) than for exercise below Tlac. Furthermore, in four of five horses, a secondary, delayed increase in VO2 became evident 135.7 +/- 28.5 s after the exercise transition. This "slow component" accounted for approximately 12% (5.8 +/- 2.7 l/min) of the net increase in exercise VO2. We conclude that, at exercise intensities below and above Tlac, qualitative features of VO2 kinetics in the horse are similar to those in humans. However, at speeds below Tlac the fast component of the response is more rapid than that reported for humans, likely reflecting different energetics of O2 utilization within equine muscle fibers.

Animals↗

Effect of increased muscle temperature on oxygen uptake kinetics during exercise.

To test whether increased muscle temperature (Tm) would improve O2 uptake (VO2) kinetics, seven men performed transitions from rest to a moderate work rate [below the estimated lactate threshold (LTest)] and a heavy work rate (VO2 = 50% of the difference between LTest and peak VO2) under conditions of normal Tm (N) and increased Tm (H), produced by wearing hot water-perfused pants before exercise. Quadriceps Tm was significantly higher in H, but rectal temperature was similar for the two conditions. There were no significant differences in the amplitudes of the fast component of VO2 or in the time constants of the on and off transients for moderate and heavy exercise between the two conditions. The increment in VO2 between the 3rd and 6th min of heavy exercise was slightly but significantly smaller for H than for N. These data suggest that elevated Tm before exercise onset, which would have been expected to increase O2 delivery and off-loading to the muscle, had no appreciable effect on the fast exponential component of VO2 kinetics (invariant time constant). These data further suggest that elevated Tm does not contribute to the slow component of VO2 during heavy exercise.

Adult↗

Effect of hypoxia and carbon monoxide on muscle oxygenation during exercise.

We used near-infrared spectroscopy (NIRS) to test the hypothesis that reducing oxygen availability during exercise would affect the rate of muscle oxyhemoglobin (O2Hb) desaturation when performing work above the lactic acidosis threshold (LAT), but not below it. Seven healthy men each performed two constant work intensities (60%LAT and the LAT plus 40% of the difference between the LAT and VO2max [40%delta]) four times under the following conditions: (1) 10 min air; (2) 5 min 15%O2 + 5 min air; (3) 5 min air + 5 min 15%O2; (4) 5 min after carbon monoxide (CO) loading to increase the carboxyhemoglobin (COHb) saturation to 15%. During each test, cardiorespiratory parameters and muscle oxygenation measured with NIRS were continuously monitored. Forearm venous blood lactate was measured every 2 to 3 min. Hypoxia and CO accelerated muscle deoxygenation only for exercise above the LAT; for exercise below the LAT, neither progressive deoxygenation nor lactate accumulation occurred after initital, rapid muscle deoxygenation. The rate of decrease in muscle oxygenation between 3 to 5 min of exercise correlated with the increase in VO2 (r = 0.61, p < 0.01) and blood lactate (r = 0.70, p < 0.01) over the same period. These results support the hypothesis that progressive muscle deoxygenation occurs above the LAT and that the rate of deoxygenation is sensitive to oxygen delivery.

Adult↗

Effect of exercise training on energy expenditure, muscle volume, and maximal oxygen uptake in female adolescents.

OBJECTIVES: American female adolescents are at high risk of a physically inactive lifestyle that likely leads to health problems later in life. We hypothesized that a brief program of endurance exercise training in female adolescents would result in increased energy expenditure and quantifiable structural and functional adaptations. STUDY DESIGN: Forty-four high school girls (aged 15 to 17 years, none were elite athletes) enrolled in a 5-day per week anatomy class for 5 weeks and were randomly assigned to control (n = 22) and training groups. All subjects participated in a 2-hour daily teaching program. During the remaining time (2 hours), the training group members underwent endurance-type training and control group subjects participated in a computer workshop. The intervention was assessed by (1) comparison of total energy expenditure between groups with the doubly labeled water technique, (2) determination of changes in thigh muscle volume by magnetic resonance imaging, and (3) determination of changes in maximal oxygen uptake by use of respiratory gas exchange responses. RESULTS: Total energy expenditure was significantly greater (15.3%) in the training group compared with the control subjects (p < 0.003). Five weeks of training led to a 4.3% +/- 1% increase in thigh muscle volume (p < 0.0002) and a 12.1% +/- 3.7% increase in maximal oxygen uptake (p < 0.004); there were no changes in the control group. The training effect was most pronounced in the least fit subjects. CONCLUSIONS: Exercise training programs for female adolescents can be successfully integrated into a high school summer curriculum. Quantifiable, substantial structural and functional responses occur with relatively short periods of training. Approximately 60% of the training response was related to factors independent of muscle size per se. These data may serve to better design physical activity programs for female adolescents.

Adolescent↗

Changes in gas exchange kinetics with training in patients with spinal cord injury.

We examined the ability of patients with spinal cord injury to undergo adaptations to chronic exercise training (cycle ergometry) invoked by functional electrical stimulation (FES) of the legs. Nine such patients performed incremental and constant work rate exercise before and after exercise training. Exercise sessions averaged 2.1 +/- 0.4/wk, and consisted of 30 min/session of continuous FES recumbent cycling with increasing work rate as tolerated. Peak VO2 and peak work rate significantly improved with training. Peak VO2 was significantly correlated with peak heart rate both before and after training (r = 0.97 pre and 0.85 post, P < 0.01 for both). The time course of the VO2, VCO2 and VE responses to constant-load exercise (unloaded cycling) and in recovery (mean response time MRT) were very long prior to training, and became significantly faster following training. However, there was no correlation between percentage improvement in either MRTon or MRToff for VO2 and the percentage increase in peak VO2. Exercise tolerance in these patients with spinal cord injury appears to be a direct function of the ability to increase heart rate. Further, exercise training can elicit significant improvements in both exercise tolerance and in gas exchange kinetics, even when performed only twice per week. However, these improvements may be accomplished by different mechanisms.

Adaptation, Physiological↗

Influence of muscle fiber type and pedal frequency on oxygen uptake kinetics of heavy exercise.

We tested the hypothesis that the amplitude of the additional slow component of O2 uptake (VO2) during heavy exercise is correlated with the percentage of type II (fast-twitch) fibers in the contracting muscles. Ten subjects performed transitions to a work rate calculated to require a VO2 equal to 50% between the estimated lactate (Lac) threshold and maximal VO2 (50% delta). Nine subjects consented to a muscle biopsy of the vastus lateralis. To enhance the influence of differences in fiber type among subjects, transitions were made while subjects were pedaling at 45, 60, 75, and 90 rpm in different trials. Baseline VO2 was designed to be similar at the different pedal rates by adjusting baseline work rate while the absolute increase in work rate above the baseline was the same. The VO2 response after the onset of exercise was described by a three-exponential model. The relative magnitude of the slow component at the end of 8-min exercise was significantly negatively correlated with % type I fibers at every pedal rate (r = 0.64 to 0.83, P < 0.05-0.01). Furthermore, the gain of the fast component for VO2 (as ml.min-1.W-1) was positively correlated with the % type I fibers across pedal rates (r = 0.69-0.83). Increase in pedal rate was associated with decreased relative stress of the exercise but did not affect the relationships between % fiber type and VO2 parameters. The relative contribution of the slow component was also significantly negatively correlated with maximal VO2 (r = -0.65), whereas the gain for the fast component was positively associated (r = 0.68-0.71 across rpm). The amplitude of the slow component was significantly correlated with net end-exercise Lac at all four pedal rates (r = 0.64-0.84), but Lac was not correlated with % type I (P > 0.05). We conclude that fiber type distribution significantly affects both the fast and slow components of VO2 during heavy exercise and that fiber type and fitness may have both codependent and independent influences on the metabolic and gas-exchange responses to heavy exercise.

Adult↗

Effects of hypoxic hypoxia on O2 uptake and heart rate kinetics during heavy exercise.

It is unclear whether hypoxia alters the kinetics of O2 uptake (VO2) during heavy exercise [above the lactic acidosis threshold (LAT)] and how these alterations might be linked to the rise in blood lactate. Eight healthy volunteers performed transitions from unloaded cycling to the same absolute heavy work rate for 8 min while breathing one of three inspired O2 concentrations: 21% (room air), 15% (mild hypoxia), and 12% (moderate hypoxia). Breathing 12% O2 slowed the time constant but did not affect the amplitude of the primary rise in VO2 (period of first 2-3 min of exercise) and had no significant effect on either the time constant or the amplitude of the slow VO2 component (beginning 2-3 min into exercise). Baseline heart rate was elevated in proportion to the severity of the hypoxia, but the amplitude and kinetics of increase during exercise and in recovery were unaffected by level of inspired O2. We conclude that the predominant effect of hypoxia during heavy exercise is on the early energetics as a slowed time constant for VO2 and an additional anaerobic contribution. However, the sum total of the processes representing the slow component of VO2 is unaffected.

Adult↗

Sublingual testosterone replacement improves muscle mass and strength, decreases bone resorption, and increases bone formation markers in hypogonadal men--a clinical research center study.

To study the effects of androgen replacement therapy on muscle mass and strength and bone turnover markers in hypogonadal men, we administered sublingual testosterone (T) cyclodextrin (SLT; 5 mg, three times daily) to 67 hypogonadal men (baseline serum T, < 8.4 nmol/L) recruited from 4 centers in the U.S.: Torrance (n = 34), Durham (n = 12), New York (n = 9), and Salem (n = 12). Subjects who had received prior T therapy were withdrawn from injections for at least 6 weeks and from oral therapy for 4 weeks. Body composition, muscle strength, and serum and urinary bone turnover markers were measured before and after 6 months of SLT. We have shown previously that this regimen for 60 days will maintain adequate serum T levels and restore sexual function. Total body (P = 0.0104) and lean body mass (P = 0.007) increased with SLT treatment in the 34 subjects in whom body composition was assessed. There was no significant change in total body fat or percent fat. The increase in lean body mass was mainly in the legs; the right leg lean mass increased from 8.9 +/- 0.3 kg at 0 months to 9.2 +/- 0.3 kg at 6 months (P = 0.0008). This increase in leg lean mass was associated with increased leg muscle strength, assessed by leg press (0 months, 139.0 +/- 4.0 kg; 6 months, 147.7 +/- 4.2 kg; P = 0.0038). SLT replacement in hypogonadal men led to small, but significant, decreases in serum Ca (P = 0.0029) and the urinary calcium/creatinine ratio (P = 0.0066), which were associated with increases in serum PTH (P = 0.0001). At baseline, the urinary type I collagen-cross linked N-telopeptides/creatinine ratio [75.6 +/- 7.9 nmol bone collagen equivalents (BCE/mmol] was twice the normal adult male mean (41.0 +/- 3.6 nmol BCE/mmol) and was significantly decreased in response to SLT treatment at 6 months (68.2 +/- 7.7 nmol BCE/mmol; P = 0.0304) without significant changes in urinary creatinine. Serum skeletal alkaline phosphatase did not change. In addition, SLT replacement caused significant increases in serum osteocalcin (P = 0.0001) and type I procollagen (P = 0.0012). Bone mineral density did not change during the 6 months of SLT treatment. We conclude that SLT replacement therapy resulted in increases in lean muscle mass and muscle strength. Like estrogen replacement in hypogonadal postmenopausal females, androgen replacement therapy led to decreased bone resorption and urinary calcium excretion. Moreover, androgen replacement therapy may have the additional benefit of increasing bone formation. A longer term study for several years duration would be necessary to demonstrate whether these changes in bone turnover marker levels will result in increased bone mineral density decreased fracture risks, and reduced frailty in hypogonadal men.

Administration, Sublingual↗

Physical fitness, endurance training, and the growth hormone-insulin-like growth factor I system in adolescent females.

We examined the relationship between physical fitness and circulating components of the GH-insulin-like growth factor I (IGF-I) system [i.e. GH, GH-binding protein (GHBP), IGF-I, and IGF-binding proteins 1-5 (IGFBP-1 through-5)] in adolescent females (age range, 15-17 yr). The study consisted of 1) a cross-sectional protocol (n = 23) in which GH-IGF-I components were correlated with fitness, as estimated by thigh muscle volume and maximal O2 uptake; and 2) a prospective study in which fitness, GH-IGF-I system components, and osteocalcin were examined before and after a 5-week period of endurance-type training (control, n = 6; trained, n = 10). The cross-sectional analysis revealed significant (P < 0.05) positive correlations between fitness and 1) mean 12-h overnight GH levels, 2) GHBP, and 3) IGF-I. Muscle volume was negatively correlated with both IGFBP-2 and -4. The prospective training study was associated with 1) increases in circulating osteocalcin (39 +/- 14%; P < 0.007), and 2) decreases in IGF-I (-14 +/- 5%; P < 0.05) and IGFBP-5 (-10 +/- 4%; P < 0.04). Unexpectedly, IGFBP-3 fell in both control (-8 +/- 2%; P < 0.01) and trained subjects (-5 +/- 3%; P < 0.05), and GHBP was reduced only among control subjects (-10 +/- 7%; P < 0.04). In summary, fitter adolescent girls tended to have increased mean serum GH, GHBP, and IGF-I. In contrast, brief endurance training led to increases in muscle mass and serum osteocalcin that were not accompanied by increases in GH or IGF-I. In fact, training may, in the short term, have led to a catabolic state hormonally expressed by reductions in IGF-I and IGFBP-5.

Adolescent↗

Changes in skeletal muscle oxygenation during incremental exercise measured with near infrared spectroscopy.

To determine the change in muscle oxygenation in response to progressively increasing work rate exercise, muscle oxyhemoglobin + oxymyoglobin saturation was measured transcutaneously with near infrared spectroscopy in the vastus lateralis muscle during cycle ergometry. Studies were done in 11 subjects while gas exchange was measured breath-by-breath. As work rate was increased, tissue oxygenation initially either remained constant near resting levels or, more usually, decreased. Near the work rate and metabolic rate where significant lactic acidosis was detected by excess CO2 production (lactic acidosis threshold, LAT), muscle oxygenation decreased more steeply. As maximum oxygen uptake (VO2max) was approached, the rate of desaturation slowed. In 8 of the 11 subjects, tissue O2 saturation reached a minimum which was sustained for 1-3 min before VO2max was reached. The LAT correlated with both the VO2 (r = 0.95, P < 0.0001) and the work rate (r = 0.94, P < 0.0001) at which the rate of tissue O2 desaturation accelerated. These results describe a consistent pattern in the rate of decrease in muscle oxygenation, slowly decreasing over the lower work rate range, decreasing more rapidly in the work rate range of the LAT and then slowing at about 80% of VO2max, approaching or reaching a minimum saturation at VO2max.

Acidosis, Lactic↗

Low intensity exercise training in patients with chronic heart failure.

OBJECTIVES: The present study was designed to evaluate whether a specific program of low intensity exercise training may be sufficient to improve the exercise tolerance of patients with chronic heart failure. BACKGROUND: Recent studies have shown that exercise training can improve exercise tolerance in patients with stable chronic heart failure, mainly through peripheral adaptations. These changes have been observed with exercise regimens at intensities of 70% to 80% of peak oxygen uptake and > 8 weeks. METHODS: We studied 27 patients (23 men, 4 women; mean [+/- SD] age 57 +/- 6 years) with mild chronic heart failure. We classified patients into two groups: trained group and untrained group. The trained group underwent a low intensity (40% of peak oxygen uptake) training program three times/week for 8 weeks. The untrained group performed no exercise. RESULTS: An increase in peak oxygen uptake (17%, p < 0.0001), lactic acidosis threshold (20%, p < 0.0002) and peak work load (21%, p < 0.0002) were obtained in the trained group only. Cardiac output and stroke volume were unchanged. A high correlation was found between the increases in peak oxygen uptake and volume density of mitochondria of vastus lateralis muscle (r = 0.77, p < 0.0002). CONCLUSIONS: Patients with stable chronic heart failure can achieve significant improvement in functional capacity from a low intensity exercise training regimen. The mechanism responsible for this favorable effect involves an increase in mitochondrial density, which reflects an improvement in oxidative capacity of trained skeletal muscles.

Anaerobic Threshold↗

The level and tempo of children's physical activities: an observational study.

We develop an observation system that quantifies the duration, intensity, and frequency of children's physical activities. We use this system to assess the level and tempo of energy expenditure under free-ranging, natural conditions experienced by 15 children aged 6-10 yr in southern California. Observations were recorded every 3 s during 4-h time blocks from 8:00 a.m.-8:00 p.m. Agreement among observers using the coding system was 91%. Using indirect calorimetry, calibration studies in the laboratory determined VO2 (ml.min-1.min-1) during each coded activity, and activities were categorized by intensity (low, medium, or high). Subjects were found to engage in activities of low intensity 77.1% of time and activities of high intensity 3.1% of time. The median duration of low and medium intensity activities was 6 s, of high intensity activities only 3 s with 95% lasting less than 15 s. Children engaged in very short bursts of intense physical activity interspersed with varying intervals of low and moderate intensity. These findings may be important for discovering how children's activity patterns under natural conditions influence physiological processes leading to growth and development. This study demonstrates the advantages of using an observational system that captures more than the intensity and frequency of children's activities to include duration and the length of intervals between activities of varying intensity.

Child↗

Near infrared spectroscopy and changes in skeletal muscle oxygenation during incremental exercise in chronic heart failure: a comparison with healthy subjects.

Near infrared spectroscopy (NIRS) is a noninvasive technique of monitoring tissue oxygen saturation by detecting changes in tissue absorbance of two wavelengths (850 and 760 nm) reflecting the relative oxygenation of hemoglobin and myoglobin. Aim of the present study was to determine whether changes in skeletal muscle oxygen saturation during incremental exercise detected by NIRS can reflect an impared oxygen delivery and an early onset of anaerobic metabolism in patients with chronic heart failure (CHF). We studied 19 subjects (mean age 43 +/- 16 years). Seven patients had a history of CHF with a diagnosis of ischemic cardiomyopathy (Group A) and 12 were healthy sedentary (Group B). All patients had a history of dyspnea on exertion (NY-HA II), peripheral edema, pulmonary rales and cardiac gallop sounds over the last 6 months. They were in sinus rhythm and stable clinical condition in the last 3 months. They were well matched regarding age, sex and body surface area. All subjects performed an incremental work rate test in a ramp pattern on a upright cycle ergometer until volitional fatigue. Gas exchange was measured breath by breath with a metabolic chart. Muscle oxygenation was determined, transcutaneously, during the exercise test over the vastus lateralis muscle with NIRS. At peak exercise, work rate, VO2, anaerobic threshold (LAT), heart rate and systolic blood pressure were significantly lower in Group A compared to Group B (92 +/- 28 vs 232 +/- 17 watts; 14 +/- 2 vs 21 +/- 2 ml/kg/min; 868 +/- 225 vs 1317 +/- 354 ml/min; 149 +/- 7 vs 172 +/- 18 b/min; 145 +/- 18 vs 195 +/- 21 mm Hg, respectively; p < 0.0001 for all). In both groups, as work rate increased, tissue oxygenation initially either remained constant near resting levels or decreased. In both groups, muscle oxygenation decreased more steeply near the work rate where lactic acidosis (LAT) was detected. However, patients with CHF had an earlier acceleration in muscle deoxygenation compared to the other group, indicating a premature onset of anaerobic metabolism. Moreover, Group A had a flatter increase in both heart rate and systolic blood pressure and a steeper slope of oxygenation profile at all matched workloads compared to normals (Group A: -0.13 +/- 0.03 ml/min; Group B: -0.06 +/- 0.015 ml/min; p < 0.0001). The LAT correlated with the work rate at which the rate of tissue O2 desaturation accelerated (r = 0.94; p < 0.0001).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Skeletal muscle oxygenation during constant work rate exercise.

We compared the slow rise in VO2 during heavy exercise (i.e., greater than lactic acidosis threshold (LAT)) with changes in muscle oxyhemoglobin+oxymyoglobin (O2Hb/O2Mb) saturation by reflectance near infrared spectroscopy. Ten subjects performed four 6-min cycle ergometer tests with two constant work rates less than and two greater than the LAT, equivalent to 20, 40, 65 and 75% peak VO2. During less than LAT exercise, O2Hb/O2Mb saturation decreased to a minimum by 2 min and then remained constant or rose slightly. For greater than LAT work rates, the initial fall in O2Hb/O2Mb saturation was greater the higher the work rate and continued to decrease with time after 3 min. Between minutes 3 and 6, the rate of decrease in O2Hb/O2Mb saturation correlated with the increase in VO2 (r = -0.69, P < 0.0001). These studies support the hypothesis that the slow rise in VO2 during heavy constant work rate exercise is associated with a progressive decline in O2Hb/O2Mb saturation in the contracting muscles themselves that may be facilitated by capillary oxyhemoglobin dissociation owing to tissue lactic acidosis (Bohr effect).

Adult↗

Gas exchange kinetics during functional electrical stimulation in subjects with spinal cord injury.

We examined the kinetics of VO2, VCO2, and VE following the onset of unloaded leg cycling, and in recovery, in six patients with spinal cord injury (SCI). Exercise was produced by functional electrical stimulation (FES) of the quadriceps, hamstrings, and gluteal muscles. End-exercise VO2 (1.03 +/- 0.16 l.min-1), VCO2 (1.20 +/- 0.22 l.min-1) and VE (41 +/- 10 l.min-1) were elevated compared to values typically seen in healthy ambulatory subjects performing similar unloaded cycling. Mean response times for the on transients (MRTon) were both long and variable across subjects for VO2 (165 +/- 62 s), VCO2 (173 +/- 58 s), and VE (202 +/- 61 s). Recovery kinetics showed much less intersubject variability, and for five of six subjects were faster than the equivalent exercise MRT for all three variables (MRToff for VO2 of 103 +/- 28 s, VCO2 136 +/- 20 s, and VE 144 +/- 34 s), but P > 0.05 for all three. Size of the O2 deficit (1.96 +/- 0.90 l) and end-exercise lactate (7.05 +/- 1.65 mmol.l-1) were similar to values reported for healthy sedentary subjects performing maximal voluntary exercise, but the end-exercise heart rate (102 +/- 16 bpm) was lower than expected for this intensity of exercise. In conclusion, FES-induced unloaded cycling leads to exaggerated responses of pulmonary gas exchange and long time constants in patients with SCI. The delayed kinetics may be due in part to a blunted increase in heart rate in addition to severe deconditioning.

Adult↗

Muscle energetics and pulmonary oxygen uptake kinetics during moderate exercise.

The present study tested whether, during moderate exercise, 1) the dynamic responses of ADP and changes in free energy of ATP hydrolysis (delta GATP) were similar to those of phosphocreatine [PCr; as would be expected for a simple controller of muscle respiration (QO2)] and 2) the rise in pulmonary O2 uptake (VO2) during cycle exercise would reflect the rise in muscle QO2 indicated by the calf PCr kinetics. The responses of PCr, Pi, ADP, and delta GATP were measured from the calf in five subjects during supine treadle exercise using 31P-magnetic resonance spectroscopy and compared with those for VO2, measured breath by breath during upright cycle exercise. The time constants for delta GATP [24.2 +/- 14.2 (SE) s] were not significantly different from those for PCr (26.3 +/- 17.3 s) and Pi (30.7 +/- 22.5 s) (P > 0.05). The time constants for phase 2 VO2 (29.9 +/- 16.8 s) were also similar to those of PCr. In contrast, the dynamics of ADP were distorted from those of PCr due to dynamic changes in pH. These results are consistent with mechanisms of respiratory control that feature substrate control by PCr or thermodynamic control through changes in delta GATP. However, these results are not consistent with substrate control by ADP in a simple fashion. Furthermore, the similarity of time constants for phase 2 VO2 and muscle PCr suggests that phase 2 VO2 kinetics reflect those of muscle QO2 in healthy subjects during moderate exercise.

Adenine Nucleotides↗

Changes in potential controllers of human skeletal muscle respiration during incremental calf exercise.

The purpose of this study was to evaluate the consequences of non-linear changes in phosphocreatine (PCr) and pH during incremental calf exercise on estimates of ADP and cytosolic free energy of ATP hydrolysis (delta GATP). Six subjects performed incremental plantar flexion exercise on a treadle ergometer while muscle P(i) metabolism (PCr, P(i), ATP) and pH were followed using 31P-nuclear magnetic resonance spectroscopy. Changes in ADP and delta GATP were estimated with the assumption that there was equilibrium of the creatine kinase reaction and homogeneous tissue metabolite pools. All six subjects showed a threshold for onset of cellular acidosis that occurred on average at 47.3 +/- 12.7% of peak work rate (PWR). In five of the six subjects, PCr and P(i) showed accelerated rates of change above the threshold for onset of cellular acidosis. In all six subjects, ADP, when correctly calculated considering changes in pH, rose in a curvilinear fashion that was well described by a Michaelis-Menten hyperbola through 60-100% of PWR, with a mean apparent Michaelis-Menten constant of 43.1 +/- 17.1 microM ADP and a predicted maximal oxidative rate at PCr = 0, which was 241 +/- 94% of PWR. delta GATP rose linearly with work rate from -62.9 +/- 1.8 kJ/mol during unloaded treadling to -55.0 +/- 1.8 kJ/mol at PWR. If we assume a linear O2 uptake-to-work rate relationship, these results are most consistent with control of respiration being exerted through delta GATP under these conditions (incremental exercise by human calf muscle).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗