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Biomedical subjects

C J Toews

Publications and source records attributed to C J Toews.

At least 19 recordsLinked to original sources

Activation of human muscle pyruvate dehydrogenase with activity and immobilization.

The activity of pyruvate dehydrogenase (PDH) was measured in samples of triceps muscle obtained in 15 males, before and after immobilization for 5 weeks and 5 months of strength training carried out in random order with cross-over of treatment. Although the total PDH activity was unchanged at 300 nmol min-1 g-1, the proportion in the active form increased after strength training (62 +/- 10.1%) and decreased after immobilization (12 +/- 2.3%) compared with control (36 +/- 3.4%). In six subjects measurements were repeated after 10 min maximal exercise (arm ergometer). The proportion of PDH in the active form increased least after immobilization (to 52 +/- 13.6%), compared with control (95 +/- 11.7%) and post-training (98 +/- 6.6%). After exercise muscle glycogen fell to the greatest extent and lactate rose the least in the post-training state, with opposite findings post-immobilization, suggesting that PDH activation contributes to the control of lactate formation in muscle during heavy exercise, and that the effects of training and immobilization are mediated at least in part through changes in the activation of this regulatory enzyme.

Adult↗

Acute reversal of the enhanced insulin action in trained athletes. Association with insulin receptor changes.

We studied the effect of aerobic training and detraining on insulin-stimulated glucose disposal and on erythrocyte insulin receptor binding. Seven endurance-trained athletes were studied at 12 h, 60 h, and 7 days after cessation of training and compared with three untrained, age- and weight-matched controls. The metabolic clearance rate of glucose as measured by the euglycemic clamp technique was 15.6 +/- 1.8 ml/kg/min (mean +/- SEM) in the trained subjects 12 h after the last bout of exercise compared with 7.8 +/- 1.2 ml/kg/min in the untrained control group. When the trained subjects refrained from physical training, the metabolic clearance rate decreased to 10.1 +/- 1.0 ml/kg/min at 60 h and further to 8.5 +/- 0.5 ml/kg/min after 7 days of detraining. The percentage of specific insulin binding to young erythrocytes (density 1.089-1.092), isolated by density gradient centrifugation, decreased from 10.4 +/- 0.9 at 12 h after the last exercise to 8.1 +/- 0.7%/3 X 10(9) cells after 60 h of detraining (P less than 0.001). The decrease in insulin binding to erythrocytes was almost entirely accounted for by a decrease in the number of insulin receptors. We conclude that the increase in peripheral insulin action seen in trained athletes is rapidly reversed, possibly by a mechanism separate from other phenomena associated with chronic training. The parallel findings of decreased in vivo insulin action and decreased insulin binding in young erythrocytes suggest that modulation of in vivo insulin response by detraining may be at least partially mediated by changes in insulin receptor number.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Activation by exercise of human skeletal muscle pyruvate dehydrogenase in vivo.

1. The activity of pyruvate dehydrogenase in its active and inactive forms was measured in biopsy samples obtained from the vastus lateralis muscle of healthy subjects before and after exercise. 2. At rest, 40 +/- 4% (mean +/- SEM) of the enzyme was in the active form. 3. After progressive aerobic exercise to exhaustion (n = 5), 88 +/- 2.3% was in the active form. 4. After intermittent supramaximal short-term exercise (1 min exercise, 3 min rest) to exhaustion (n = 6), 60 +/- 2.2% was in the active form. 5. After isometric maximal exercise of 65 +/- 3.6 s duration (n = 3), only 39 +/- 1% of the enzyme was in the active form. 6. Muscle glycogen depletion was greatest with intermittent exercise and least with isometric maximal exercise; in contrast, the increase in muscle lactate was least with progressive exercise (1.3 to 9.4 mumol/g), intermediate in intermittent maximal exercise (1.2 to 13.1 mumol/g) and greatest after isometric exercise (1.8 to 17.6 mumol/g). There were no significant differences between the three studies in the changes in lactate/pyruvate ratios. 7. In three subjects who exercised with one leg, activation of the enzyme was twice as great in the exercise as in the inactive leg. 8. The ratio of active to total enzyme in biopsies of resting muscle was greater in four well-trained athletes than in four untrained control subjects (70% compared with 41% respectively). 9. The activation of pyruvate dehydrogenase appears to play an important part in regulating the use of glycogen and glucose during exercise in man.

Adult↗

Effect of PH on muscle glycolysis during exercise.

1. Five males were studied on three occasions, after oral administration of CaCO3 (control), NH4Cl (acidosis) and NaHCO3 (alkalosis), in a dose of 0.3 g/kg, taken over a 3 h period at rest. The subjects then exercised on a cycle ergometer for 20 min at 33% maximal oxygen uptake (VO2 max.), followed by 20 min at 66% and at 95% VO2 max. until exhaustion. 2. Endurance at 95% VO2 max. was longest with alkalosis (5.44 +/- 1.05 min), shortest with acidosis (3.13 +/- 0.97 min) and intermediate in the control study (4.56 +/- 1.31 min); venous blood pH at exhaustion was 7.33 +/- 0.02 (mean +/- 1 SEM), 7.13 +/- 0.02 and 7.26 +/- 0.02 respectively. 3. Concentrations of plasma lactate at exhaustion were 7.10 +/- 0.8 mmol/1 4.0 +/- 0.5 and 7.9 +/- 0.9 mmol/l in the control, acidosis and alkalosis studies respectively. 4. Muscle lactate increased most from rest to exhaustion with alkalosis to 17.1 +/- 2.5 mumol/g and least with acidosis to 12.2 +/- 1.4 mumol/g. Muscle glycogen depletion was comparable in control and alkalosis studies. 5. The lower plasma lactate concentration during exercise in acidosis compared with control and alkalosis appears to be due to an inhibition of muscle glycolysis combined with a reduction in lactate efflux from muscle.

Acidosis↗

Effects of menstrual cycle on blood lactate, O2 delivery, and performance during exercise.

The effects of the menstrual cycle on cardiorespiratory variables, blood lactate, and performance were studied in exercising females. Nine healthy subjects, 20--24 yr of age, were investigated in midfollicular and midluteal phases of the menstrual cycle at 33, 66, and 90% of maximum power output (light, heavy, and exhaustive exercise). Occurrence of ovulation was confirmed in all subjects by measurement of progesterone, which increased from 0.6 +/- 0.1 (mean +/- SE) in the follicular to 8.9 +/- 2.2 ng/ml in the luteal phase. There was no difference in heart rate (HR), ventilation, O2 uptake, or CO2 output between the two phases during light and heavy exercise, and there was no difference in HR at exhaustion. Cardiac output measured midway through light and heavy exercise periods was not affected by the phase of testing. Time for which exhaustive exercise could be maintained increased from 1.57 +/- 0.32 in the follicular to 2.97 +/- 0.63 min in the luteal phase (P less than 0.02). Blood lactate was higher in the follicular phase after heavy exercise (6.62 +/- 0.8 vs. 4.92 +/- 0.5 mmol/l) (P less than 0.05) and at exhaustion (8.12 +/- 0.9 vs. 6.76 +/- 0.6 mmol/L) (P less than 0.01). A further study showed no effect of cycle phase on lactate disappearance during exercise. We conclude that while aerobic performance and the cardiorespiratory adaptations to exercise are not influenced by the phase of the menstrual cycle, performance of high-intensity exercise is improved, and lactate production appears to be decreased in the luteal phase when estradiol and progesterone levels are elevated.

Adult↗

Purine metabolism during strenuous muscular exercise in man.

This study was designed to examine the influence of exercise on purine metabolism in man. In 15 men, the plasma uric acid concentration increased from 6.9 to 8.5 mg/dl following a 5000-m race and from 6.2 to 7.9 mg/dl in 11 men following a 42-km marathon. During a progressive exercise test on a cycle ergometer, the plasma uric acid ocnentration did not change significantly in 11 subjects. However, the plasma oxypurines increased from 19 micrM at rest to 50 microM at exhaustion and the urinary excretion of oxypurines increased from 140 to 400 mumol/g creatinine. Intracellular ATP decreased from 5.17 to 2.91 mumol/g and ADP and AMP increased from 0.85 to 1.29 and from 0.12 to 0.15 mumol/g wet weight, respectively. These observations suggest that there is an accelerated degradation of purine nucleotides to the precursors of uric acid in skeletal muscle during vigorous exercise.

Adenine Nucleotides↗

Fat metabolism in heavy exercise.

1. To investigate differences between the metabolic effects of light and heavy exercise, five healthy males (mean maximal oxygen intake 3.92 litres/min) exercised for 40 min at 36% maximum power (light work) and 70% maximum power (heavy work) on separate days, after an overnight fast. 2. A steady state was achieved in both studies between 20 and 40 min in: oxygen intake (1.42 and 2.64 litres/min respectively); respiratory exchange ratio (0.89 and 1.01); plasma lactate concentration (1.78 and 9.94 mmol/l). 3. Plasma palmitate turnover rate (14C) was unchanged from resting values in light work but was decreased by 40% (from 104 +/- 16 to 63 +/- 8 micronml/min) in heavy work. Heavy work was associated with falls in the plasma concentrations of all free fatty acids measured: palmitic acid (C16:0), oleic acid (C18:1), stearic acid (C18:0), linoleic acid (C18:2) and palmitoleic acid (C16:1). 4. In contrast to th fall in palmitate turnover the increase in plasma glycerol was greater in heavy exercise (0.054-0.229 mmol/l) than in light exercise (0.053-0.094 mmol/l), suggesting that lipolysis was occurring which did not lead to influx of free fatty acids into plasma. 5. In light exercise fat metabolism may be controlled to favour adipose tissue lipolysis and extraction of free fatty acids by muscle from the circulation, whereas in heavy exercise adipose tissue lipolysis is inhibited and hydrolysis of muscle triglycerides may play a more important part. 6. The finding of a high respiratory exchange ratio may not exclude the use of fat as a major fuel source in exercise associated with lactate production.

Adult↗

Synthesis of antithrombin III and alpha-1-antitrypsin by the perfused rat liver.

Livers isolated from control or turpentine-injected rats were perfused for 3 h with human red cells suspended in Krebs-Henseleit solution containing bovine serum albumin, dextran, glucose, heparin, cortisol, insulin, a mixture of 20 amino acids and [3H]leucine. Changes in the concentrations of antithrombin III and alpha-1-antitrypsin were evaluated by rocket immunoelectrophoresis using specific antisera, and incorporation of the 3H radioactivity into the total protein, albumin, antitrhombin III and alpha-1-antitrypsin in the perfusate was measured. The results indicate that both antithrombin III and alpha-1-antitrypsin are synthesized in the liver. Local inflammation induced in the liver donors moderately stimulated the synthesis of alpha-1-antitrypsin but it affected only marginally that of antithrombin III.

Albumins↗

Effect of pH on cardiorespiratory and metabolic responses to exercise.

Five male subjects performed exercise at 33, 66, and 95% of their maximum power output on three occasions in random order. Each study was preceded by a 3-h period in which capsules were taken by mouth, containing either CaCO3 (control, NH4Cl (acidosis), or NaHCO3 (alkalosis) in a dose of 0.3 g/kg body wt; preexercise blood pH was 7.38 +/- 0.015, 7.21 +/- 0.033, and 7.43 +/- 0.029, respectively. Exercise was continuous and maintained for 20 min at the two lower power outputs and for as long as possible at the highest. Compared with control (270 +/- 13 s), endurance time at the highest power output was reduced in acidosis (160 +/- 22 s) and increased in alkalosis (438 +/- 120 s). No differences were observed for central cardiovascular changes in exercise (cardiac output, frequency, or stroke volume). The respiratory changes expected from changes in blood pH were observed, with a higher alveolar ventilation in acidosis. At all power outputs arterialized venous lactate was lowest in acidosis and highest in alkalosis. Plasma glycerol and free fatty acids were lowest in acidosis. Changes in blood [HCO3-] and pH were shown to have major effects on metabolism in exercise which presumably were responsible for impaired endurance.

Acidosis↗

Growth hormone secretion in acid-base alterations at rest and during exercise.

1. Seven healthy males were studied during cycle ergometer exercise at 33%, 66% and 90% of VO2 max. on three occasions when NH4C1, NaHCO3 or CaCO3 (as a control substance) were administered in gelatin capsules double blind and in randomized order. Plasma growth hormone (HGH), lactic acid and hydrogen ion concentration ([H+]) were measured at frequent intervals. 2. Ammonium chloride produced highest blood [H+] and NaHCO3 the lowest. These differences were maintained during exercise and in recovery. Plasma lactic acid concentrations were similar at rest. At 66%, 90% VO2 max. and recovery lactic acid was highest with NaHCO3 and lowest with NH4C1. 3. Exercise stimulated HGH secretion in all studies and the elevation was proportional to the intensity of the exercise. NH4C1 caused a variable elevation of HGH at rest and 33% VO2 max. At 66% VO2 max., plasma HGH was significantly elevated to similar concentrations in all studies and, at 90% VO2 max., HGH was highest with NaHCO3. 4. An infusion of sodium L(+)-lactate producing plasma lactate concentrations of 3-5 mmol/l did not influence HGH secretion. 5. Exercise is a physiological stimulus to HGH secretion and the mechanism is independent of blood [H+] and lactate concentrations.

Acid-Base Equilibrium↗