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Biomedical subjects

A Nadeau

Publications and source records attributed to A Nadeau.

At least 127 records · Page 7Linked to original sources

The response to long-term overfeeding in identical twins.

We undertook this study to determine whether there are differences in the responses of different persons to long-term overfeeding and to assess the possibility that genotypes are involved in such differences. After a two-week base-line period, 12 pairs of young adult male monozygotic twins were overfed by 4.2 MJ (1000 kcal) per day, 6 days a week, for a total of 84 days during a 100-day period. The total excess amount each man consumed was 353 MJ (84,000 kcal). During overfeeding, individual changes in body composition and topography of fat deposition varied considerably. The mean weight gain was 8.1 kg, but the range was 4.3 to 13.3 kg. The similarity within each pair in the response to overfeeding was significant (P less than 0.05) with respect to body weight, percentage of fat, fat mass, and estimated subcutaneous fat, with about three times more variance among pairs than within pairs (r approximately 0.5). After adjustment for the gains in fat mass, the within-pair similarity was particularly evident with respect to the changes in regional fat distribution and amount of abdominal visceral fat (P less than 0.01), with about six times as much variance among pairs as within pairs (r approximately 0.7). We conclude that the most likely explanation for the intrapair similarity in the adaptation to long-term overfeeding and for the variations in weight gain and fat distribution among the pairs of twins is that genetic factors are involved. These may govern the tendency to store energy as either fat or lean tissue and the various determinants of the resting expenditure of energy.

Adult↗

Correlates of plasma very-low-density lipoprotein concentration and composition in premenopausal women.

Potential correlates of plasma very-low-density lipoprotein (VLDL) concentration and composition were studied in a sample of 75 premenopausal women. Fasting plasma free fatty acid (FFA) levels, as well as plasma glucose and insulin levels in the fasting state and during an oral glucose tolerance test, displayed significant positive correlations with plasma triglyceride (TG) and VLDL-TG levels (P less than .005). Plasma post-heparin lipoprotein lipase (LPL) activity, measured in a subsample of 31 women from the original sample, was negatively correlated with plasma TG, VLDL-cholesterol (CHOL), VLDL-TG, and VLDL-apolipoprotein (apo) B concentrations (.005 greater than P less than .05). Multivariate analyses showed that, after LPL was considered, the insulin area was the only other metabolic variable studied that was significantly correlated with VLDL-apo B concentration, whereas fasting FFA levels were significantly correlated with plasma TG and VLDL-TG levels. ANOVA revealed that plasma VLDL-CHOL, VLDL-TG, and VLDL-apo B levels were not associated with the glucose area, but were significantly associated with the insulin area (P less than .005). When the effect of insulin area was controlled for, the plasma FFA levels did not contribute significantly to the variance in VLDL-CHOL and VLDL-apo B, but showed an independent effect on VLDL-TG levels (P less than .05). Finally, stepwise multiple regression analyses indicated that once the variance explained by plasma LPL activity and by the insulin area was considered, no other metabolic variable could account for the variation in VLDL-CHOL and VLDL-apo B levels, whereas fasting FFA levels explained a further 5% of the VLDL-TG variance and one third of the variance observed in the VLDL-TG/apo B ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Counterregulatory response to insulin-induced hypoglycemia in trained and nontrained humans.

The aim of the present series of experiments was to investigate the hormonal counterregulatory response to insulin-induced hypoglycemia in trained and nontrained healthy individuals. Five endurance athletes and six controls were administered intravenous insulin infusion at a rate of 0.15 U/kg/h until plasma glucose reached 50 mg/dL. The mean duration of the infusion in the trained and nontrained subjects corresponded to 18.6 and 26.3 minutes (P less than .01), suggesting that the former were characterized by an increased insulin sensitivity. Plasma glucose levels were similar in the two groups at the end of the insulin infusion, as well as during the postinfusion recovery period. Forty-five minutes after the end of the infusion, plasma glucose levels were not significantly different from the preinfusion levels in the two groups. During this period of glycemia recovery, the increases in plasma glucagon, epinephrine, norepinephrine, and growth hormone were at least 50% lower in the trained than in the nontrained subjects. The increase in heart rate and oxygen uptake during the same period of time was significantly higher in the trained subjects. To determine whether this reduced hormonal response to hypoglycemia was due to reduced insulin levels or to an increased sensitivity to counterregulatory hormones, we investigated the effect of epinephrine on plasma glucose in two other groups of trained and nontrained subjects. In response to a constant epinephrine infusion of 0.01 or 0.1 micrograms/kg fat-free mass (FFM)/min, plasma glucose levels increased similarly in the two groups. In conclusion, these results indicate that trained subjects are characterized by a normal recovery from hypoglycemia despite a reduced response of counterregulatory factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗

Abdominal fat cell lipolysis, body fat distribution, and metabolic variables in premenopausal women.

It is well established that abdominal obesity is related to numerous metabolic abnormalities and that this correlation represents a significant risk factor for coronary heart disease and related mortality. In the present study the relationships among the regional distribution of body fat, selected metabolic variables, and abdominal adipose cell lipolysis were investigated in 30 premenopausal women, 34 +/- 8 yr (mean +/- SD) of age, with body mass indices ranging from 17-45 kg/m2. Basal as well as epinephrine- and isoproterenol-stimulated lipolyses were positively correlated with fasting plasma insulin and triglyceride levels (0.48 less than r less than 0.64; 0.05 greater than P less than 0.0005 and 0.46 less than r less than 0.60; 0.05 greater than P less than 0.005, respectively) and with the insulin area measured during an oral glucose tolerance test (0.49 less than r less than 0.67; 0.005 greater than P less than 0.0005). With the exception of epinephrine-stimulated lipolysis, these correlations remained significant when lipolysis was corrected for cell surface area. Basal and maximal epinephrine- and isoproterenol-induced lipolyses were also negatively related to plasma high density lipoprotein cholesterol (-0.52 less than r less than -0.36; 0.05 greater than P less than 0.005). However, these relationships were no longer significant after control for fat cell surface. The associations between abdominal lipolysis and fat distribution did not remain significant when data were adjusted for total adiposity. Taken together, these results support the notion that variations in abdominal adipocyte lipolysis 1) depend more on total body fatness than on fat distribution, and 2) may be involved in the metabolic complications associated with abdominal obesity, particularly those pertaining to plasma insulin and triglyceride metabolism.

Abdominal Muscles↗

Altered plasma free carnitine response to exercise in type 1 diabetic subjects.

The plasma carnitine response to prolonged exercise in 12 postprandial insulin-dependent diabetics was compared with that of eight normal controls. The diabetics reduced their morning dose of intermediate acting insulin and regular insulin to two-thirds and one-half, respectively. Insulin was injected subcutaneously into the abdominal wall. Exercise was performed on a treadmill for 90 min at 60% VO2 max. Respiratory exchange ratios (RER) decreased significantly (p less than 0.0001) during exercise in both the control and diabetic group. However, RER values were higher (p less than 0.05) in the diabetic group during most of the exercise period, corresponding to a significantly (p less than 0.05) lower proportion of the energy utilized from the oxidation of fat. In the diabetic group, mean plasma glucose at rest was 278 +/- 26 mg/dl, and decreased significantly (p less than 0.01) to 107 +/- 12 mg/dl after 90 min of exercise. In the control group, mean resting plasma glucose was 78 +/- 6 mg/dl, and dropped (p less than 0.05) to 67 +/- 3 mg/dl at 30 min of exercise. Thereafter, it showed no change. Mean resting plasma free insulin in the control group was lower compared to the diabetic group (10.2 +/- 2.0 vs 23.5 +/- 2.0 microU/ml, p less than 0.001). During exercise, insulin levels decreased significantly (p less than 0.01) in the control group while there was no change in the diabetic group. In both control and diabetic groups, percent basal total carnitine increased significantly (p less than 0.01) throughout exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Beneficial effect of exercise training on cardiac long-chain acylcarnitine levels in diabetic rats.

Long-chain acylcarnitines are markedly elevated in the diabetic rat heart. This could be associated with the increased rate of fatty acid metabolism in this tissue seen in the diabetic animal. The effect of exercise training on this carnitine derivative in the diabetic rat, however, has received little attention. We therefore examined the effect of exercise training on this derivative as well as other carnitine esters in hearts of diabetic rats. Four groups of male Wistar rats were used: sedentary-control (SC), trained-control (TC), sedentary-diabetic (SD), and trained-diabetic (TD). Diabetes was induced by the I.V. injection of streptozotocin at the dose of 50 mg/kg. Training was performed on a motor-driven treadmill according to a 10-week program. Sixty hours after the last bout of exercise, the rats were killed by decapitation and the hearts were quickly excised and placed in liquid nitrogen for measurement of total carnitine and its acyl derivatives. SD and TD had significantly lower levels of total (p less than 0.001) and free carnitine (p less than 0.01) compared to the respective control groups. Exercise had no effect on total and free carnitine levels in both control and diabetic groups. Short-chain acylcarnitine levels were neither altered by training nor diabetes. Heart tissue levels of long-chain acylcarnitine were increased (p less than 0.01) in SD compared to SC. However, exercise training resulted in a significant (p less than 0.05) reduction in long-chain acylcarnitines in diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Acylation↗

Beneficial effect of exercise training on cardiac long-chain acylcarnitine levels in diabetic rats.

Long-chain acylcarnitines are markedly elevated in the diabetic rat heart. This could be associated with the increased rate of fatty acid metabolism in this tissue seen in the diabetic animal. The effect of exercise training on this carnitine derivative in the diabetic rat, however, has received very little attention. We therefore examined the effect of exercise training on this derivative as well as other carnitine esters in hearts of diabetic rats. Four groups of male Wistar rats were used: sedentary-control (SC), trained-control (TC), sedentary-diabetic (SD), and trained-diabetic (TD). Diabetes was induced by the I.V. injection of streptozotocin at the dose of 50 mg/kg. Training was performed on a motor-driven treadmill according to a ten-week program. 60 hr after the last bout of exercise, the rats were killed by decapitation and the hearts were quickly excised and placed in liquid nitrogen for measurement of total carnitine and its acyl derivatives. SD and TD had significantly lower levels of total (p less than 0.001) and free carnitine (p less than 0.01) compared to the respective control groups. Exercise had no effect on total and free carnitine levels in both control and diabetic groups. Short-chain acylcarnitine levels were neither altered by training nor diabetes. Heart tissue levels of long-chain acylcarnitine were increased (p less than 0.01) in SD compared to SC. However, exercise training resulted in a significant (p less than 0.05) reduction in long-chain acylcarnitines in diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Acylation↗

Physical training of moderate intensity improves survival rate of diabetic rats submitted to experimental myocardial infarction.

The present study was designed to compare the effect of three programs of exercise of different intensity on the survival rate of normal and streptozotocin-diabetic rats (60 mg/kg) submitted to acute experimental myocardial infarction. The animals were trained progressively on a treadmill once a day, five days per week for eight weeks at a 10 degree incline according to one of the following treadmill running programs: light (30 mins/day at 20 m/min), moderate (30 mins/day at 25 m/min) or heavy (60 mins/day at 25 m/min). Myocardial infarction was produced by left coronary artery ligation under ether anesthesia three days after the last bout of exercise. Successful ligation was demonstrated by elevated plasma creatine kinase MB isoenzyme levels 4 h later or by dye injection in rats with early death. In sedentary diabetic rats (n = 33), the early survival rate was decreased in comparison to sedentary controls (n = 22), although statistical significance was not reached, (30 versus 45%; P = 0.1952 by Fisher's exact test). These values were not significantly modified by light or heavy training in control (light n = 18, 61%; heavy n = 25, 56%) nor in diabetic animals (light n = 28, 32%; heavy n = 23, 39%). While the survival rate was not altered by moderate exercise in control animals (n = 26, 62%), it was greatly improved in diabetic rats (n = 23, 64%, P = 0.0108 versus sedentary diabetics). These data suggest that it is possible to improve the early survival rate of diabetic rats submitted to experimental myocardial infarction by a previous training program at a moderate level of exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Long-term exercise training with constant energy intake. 1: Effect on body composition and selected metabolic variables.

The effects of long-term negative energy balance generated by exercise while maintaining a constant energy intake were studied in five healthy young males (25 +/- 3 years; mean +/- s.d.). After 2 weeks of monitoring to determine habitual energy intake, they were subjected to a 100-day experimental period during which they exercised on a cycle ergometer, 6 days a week, twice a day at 55 per cent of VO2 max. The daily energy deficit was 4.2 MJ for a total of 353 MJ for the duration of the treatment. Body weight decreased from 86.7 to 78.7 kg (P less than 0.001). More than 80 per cent of the weight loss was accounted for by the reductions in fat mass. Fat-free mass did not change significantly. The data suggest that subcutaneous fat was lost about evenly from the trunk and from the limbs as estimated from skinfolds. Cardiorespiratory and metabolic responses to submaximal work loads indicate that the low intensity exercise regimen was capable of inducing some of the known adaptations of exercise training such as a decrease in plasma insulin and norepinephrine concentrations during exercise, reductions in heart rate, pulmonary ventilation and blood lactate concentration at a given exercise intensity, and an increase in skeletal muscle oxidative capacity. The energy cost of sitting and standing was not decreased in spite of the loss in body mass. However, the energy cost of submaximal cycling and walking exercises was reduced considerably. These results clearly demonstrate that it is quite possible to lose fat while preserving fat-free mass through regular prolonged exercise of moderate intensity if energy intake is kept constant at baseline level. They also emphasize the importance of the individual differences in response to negative energy balance.

Adult↗

Long-term exercise training with constant energy intake. 2: Effect on glucose metabolism and resting energy expenditure.

The effect of exercise training on glucose and insulin metabolism as well as on resting energy expenditure was investigated in five young men (mean BMI = 27.5 +/- 2.9 (s.d)). Subjects performed cycle-ergometer exercise 6 days/week over a 100 day period and the quantity of daily exercise was calculated to induce a 4.2 MJ/day surplus in energy expenditure during the days of training. As expected, significant weight and fat losses were observed in response to the training program. Exercise training induced a significant reduction in fasting levels and in the responses of insulin to a 4.2 MJ meal or an oral glucose load. Most of the training effects were noted after only 25 days of training. However, a significant decrease in plasma C-peptide concentrations during the oral glucose tolerance test was observed only at the end of the exercise program whereas essentially no change occurred during the first 25 days of training. The resting metabolic rate (RMR) and the thermic effect of food (TEF) were not significantly modified by training. Results show that the reduction in plasma insulin induced by training occurred earlier than that for C-peptide. Moreover, the absence of change in RMR in the presence of a substantial weight loss may represent a beneficial effect of training in comparison to the documented effect of diet-induced weight loss on RMR.

Adult↗

Long-term exercise training with constant energy intake. 3: Effects on plasma lipoprotein levels.

The composition and concentration of plasma lipoproteins were studied in five young men (mean BMI = 27.5 +/- 2.9 (s.d.] before, during (after 25 and 50 days of training), and after the completion of a 100 day exercise training program that induced daily 4.2 MJ calorie deficit. Along with reductions in body weight (from 86.7 +/- 20.0 to 78.7 +/- 17.1 kg, P less than 0.01) and in fat mass (from 17.0 +/- 9.7 to 10.4 +/- 7.4 kg, P less than 0.01), the exercise training program induced numerous changes in plasma lipoprotein levels. Plasma total cholesterol level fell significantly after 25 days of training (P less than 0.05) and remained significantly reduced at the end of the training experiment (P less than 0.05). This reduction in total plasma cholesterol was accompanied by reductions in plasma apoprotein (apo) B, LDL-cholesterol and LDL-apo B levels (P less than 0.05). There were trends for reductions in plasma triglyceride and VLDL components that were significant only for VLDL-triglycerides (P less than 0.05). Plasma HDL-cholesterol levels increased significantly only at the end of the training program (P less than 0.01). This increase in plasma HDL-cholesterol was not accompanied by an increase in plasma apo A-I levels suggesting that exercise training produced an increase in HDL cholesterol content rather than an increase in HDL particle number. Ratios of HDL-cholesterol/cholesterol (P less than 0.01) and apo A-I/apo B (P less than 0.05) were significantly increased by exercise training, suggesting a decreased risk of cardiovascular disease. These results indicate that a reduction in fat mass solely induced by aerobic exercise training has substantial beneficial effects on plasma lipoprotein levels.

Adult↗

Associations between regional body fat distribution, fasting plasma free fatty acid levels and glucose tolerance in premenopausal women.

The associations between total adiposity, body fat distribution measured by computed tomography (CT) and estimated by the waist-to-hip ratio (WHR), regional fat cell morphology, fasting plasma free fatty acid (FFA) levels and glucose tolerance were studied in a sample of 37 premenopausal women aged 35.3 +/- 4.6 years (mean +/- s.d.). Body fat mass, CT-derived abdominal and femoral fat areas, as well as the abdominal fat cell weight were all significantly associated with fasting plasma FFA levels (0.34 less than r less than 0.49, 0.005 less than P less than 0.05), and with the glucose and insulin areas during the oral glucose tolerance test (OGTT) (0.36 less than r less than 0.70, 0.0001 less than P less than 0.05). No associations were found between the WHR, the femoral fat cell weight and fasting plasma FFA levels or glucose area during the OGTT. However, the WHR and the femoral fat cell weight were positively associated with insulin area. Plasma FFA levels were positively correlated with the glucose area during the OGTT, whereas no association was found between plasma FFA levels and the insulin area. Covariance analysis indicated that this effect of plasma FFA levels on the magnitude of glucose response to OGTT was independent from that of total adiposity or regional body fat distribution variables. These results emphasize the importance of plasma FFA levels as a correlate of glucose tolerance and suggest that the associations previously reported between obesity, regional body fat distribution, fat cell size and glucose tolerance are, at least partly, mediated by variations in plasma FFA levels.

Abdomen↗

Genetic effect in resting and exercise metabolic rates.

Two studies dealing with the contribution of the genotype in individual differences for resting metabolic rate (RMR), thermic effect of a 4.2 MJ carbohydrate meal (TEM), and energy cost of submaximal exercise are reported. The genetic effect for RMR and TEM was studied in 31 pairs of parent-child, 21 pairs of dizygotic (DZ) twins, and 37 pairs of monozygotic (MZ) twins, whereas the heritability of the energy cost of submaximal exercise was determined from data on 22 pairs of DZ twins and 31 pairs of MZ twins. The heritability of RMR reached approximately 40% of the variance remaining after adjustment for age, gender, and fat-free mass, (FFM). The genetic effect for TEM was equivalent to at least 40% to 50% of the variation in the energy expended during four hours after the meal test. A highly significant genetic effect was found for fasting plasma glucose (greater than .72), but the results for fasting plasma insulin are unclear. No significant genetic variance was seen for the glucose and insulin response to the carbohydrate meal. Finally, heritability for the metabolic rate during cycle exercise was high (greater than or equal to .46) at low power output, but it became nonsignificant when the energy cost reached about 6 times the RMR.

Adolescent↗

Computed tomography-measured trunk fat and plasma lipoprotein levels in nonobese women.

The associations between total adiposity, adipose tissue distribution measured by computed axial tomography (CAT), regional variation in fat cell size, and plasma lipoprotein levels were studied in a sample of 22 premenopausal healthy nonobese women aged 34.6 +/- 3.1 years (mean +/- SD) (% body fat, 27.8 +/- 5.8). In these nonobese women, no associations were found between total adiposity, adipose tissue distribution, and plasma triglyceride or very-low-density lipoprotein levels. However, total adiposity (as reflected by the body density-derived fat mass and by the adipose tissue volume measured by CAT), as well as the total trunk fat areas (measured at the abdominal and thoracic levels) were positively correlated with plasma low-density lipoprotein (LDL) cholesterol (.05 greater than P less than .01) and LDL apolipoprotein (apo) B (.05 greater than P less than .0005) levels. Because of these associations with LDL-C and LDL apo B levels, these body fatness indicators were negatively correlated with the HDL-cholesterol/LDL-cholesterol and HDL-apo A-I/LDL-apo B ratios. However, few significant associations were observed between the proportion of abdominal fat estimated by the waist/hip circumference ratio (WHR) and the lipoprotein-lipid profile (r = .45 and r = .44, P less than .05 with HDL triglyceride (TG) and LDL-apo B/LDL-cholesterol ratio, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗

Diminished hypotensive response to isoproterenol in streptozotocin-diabetic rats.

1. The cardiovascular reactivity of streptozotocin-diabetic rats has been evaluated with isoproterenol (ISO), a strong beta-adrenergic agonist able to produce, at large dose, myocardial infarction. 2. In the basal state, diabetic rats presented significantly lower heart rate (P less than 0.001), a decreased systolic (P less than 0.05) and an unaltered diastolic blood pressure compared to non-diabetics. 3. Following ISO stimulation, the chronotropic response was similar in both groups of rats, while the fall in systolic and diastolic pressure was markedly reduced compared to those of non-diabetic rats (P less than 0.001). 4. These results suggest that the vasodilation capacity of diabetic rats is diminished.

Animals↗

Assessment of adipose tissue distribution by computed axial tomography in obese women: association with body density and anthropometric measurements.

1. Abdominal obesity is associated with numerous metabolic complications. Deep abdominal adipose tissue is critical in the association between the level of abdominal obesity and cardiovascular risk factors. 2. Adipose tissue localization was assessed by computed axial tomography (CAT), and its association with body density and anthropometric measurements was investigated in a sample of fifty-one obese women (percentage body fat 45.9 (SD 5.6)) aged 35.7 (SD 5.5) years. The CAT scans were performed at three levels: lower chest, abdomen and mid-thigh. 3. The total adipose tissue volume computed from these three scans was highly correlated with body fat mass (r 0.94, P less than 0.001). The proportion of deep abdominal fat as measured by the ratio of deep: total adipose tissue areas at the abdominal level was not significantly correlated with body fat mass, but it was moderately associated with the ratio of waist: hip circumferences (WHR) (r 0.49, P less than 0.001). The absolute amount of deep abdominal fat was, however, significantly correlated with body fat mass (r 0.72, P less than 0.001). 4. The subscapular (r 0.38) and the abdominal (r 0.38) skinfolds were the only two skinfolds that were significantly associated with the proportion of deep abdominal fat (P less than 0.01). These skinfolds were also those which showed the highest correlation with the absolute amount of deep abdominal fat (r 0.65, P less than 0.001, for both skinfolds). 5. A three-site CAT-scan procedure can be used for the estimation of body fat mass in premenopausal obese women. 6. In these obese women, there was no significant association between total adiposity and the proportion of deep adipose tissue at the abdominal level. 7. In premenopausal obese women, the absolute amount of deep abdominal fat can be predicted from anthropometric measurements with more accuracy than the relative amount of deep abdominal fat.

Adipose Tissue↗

The effect of prior exercise and caffeine ingestion on metabolic rate and hormones in young adult males.

The purposes of this study were to examine (a) the effects of acute exercise on metabolic rate 24 and 48 h postexercise and (b) the interaction of acute exercise and the thermic effect of caffeine on metabolic rate and hormonal changes during the late postexercise recovery period. In six young males, who were regular consumers of caffeine, resting energy expenditure was measured before and after caffeine (5 mg.kg-1) and placebo ingestion under the following conditions: (i) control (e.g., no prior exercise), (ii) 24 h postexercise, and (iii) 48 h postexercise. Blood samples were drawn for plasma glucose, insulin, glycerol, free fatty acids, catecholamines, and thyroid hormones (triiodothyronine, thyroxine, and free thyroxine). Results showed that acute exercise did not exert a detectable effect on resting metabolic rate in the late postexercise recovery period, that is, resting metabolic rate was similar among the conditions of control (1.17 +/- 0.12 kcal.min-1), 24 h postexercise (1.16 +/- 0.12), and 48 h postexercise (1.16 +/- 0.11). Caffeine ingestion increased metabolic rate (approximately 7%), but the thermic effect was not different among the experimental conditions. Plasma insulin and norepinephrine were lower after caffeine ingestion, whereas an increase in plasma free fatty acids was noted. Other hormones and substrates did not change significantly in response to caffeine ingestion. Furthermore, the hormonal and substrate milieu was not significantly different 24 and 48 h postexercise when compared with the control condition. Our results support the view that acute exercise does not alter the resting metabolic rate in the late postexercise recovery period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗