Substrate availability limits human skeletal muscle oxidative ATP regeneration at the onset of ischemic exercise.

We have demonstrated previously that dichloroacetate can attenuate skeletal muscle fatigue by up to 35% in a canine model of peripheral ischemia (Timmons, J.A., S.M. Poucher, D. Constantin-Teodosiu, V. Worrall, I.A. Macdonald, and P.L. Greenhaff. 1996. J. Clin. Invest. 97:879-883). This was thought to be a consequence of dichloroacetate increasing acetyl group availability early during contraction. In this study we characterized the metabolic effects of dichloroacetate in a human model of peripheral muscle ischemia. On two separate occasions (control-saline or dichloroacetate infusion), nine subjects performed 8 min of single-leg knee extension exercise at an intensity aimed at achieving volitional exhaustion in approximately 8 min. During exercise each subject's lower limbs were exposed to 50 mmHg of positive pressure, which reduces blood flow by approximately 20%. Dichloroacetate increased resting muscle pyruvate dehydrogenase complex activation status by threefold and elevated acetylcarnitine concentration by fivefold. After 3 min of exercise, phosphocreatine degradation and lactate accumulation were both reduced by approximately 50% after dichloroacetate pretreatment, when compared with control conditions. However, after 8 min of exercise no differences existed between treatments. Therefore, it would appear that dichloroacetate can delay the accumulation of metabolites which lead to the development of skeletal muscle fatigue during ischemia but does not alter the metabolic profile when a maximal effort is approached.

Early effects of short-term endurance training on hormonal responses to graded exercise.

Twelve male, sedentary volunteers (22.0 +/-) were submitted to three weeks of a bicycle ergometer training, consisting of 45 min exercise (at 70% VO2max), 4 times in the first week and 3 times in the next 2 weeks. They performed four incremental exercise tests with the power output increased by 50 W every 3 min until volitional exhaustion: two before training (C1 and C2), and after one (T1) and three (T3) weeks of training. Before and after each load the plasma noradrenaline (NA), adrenaline (A) and blood lactate (LA) concentrations were determined in venous blood samples as well as plasma growth hormone (HGH) and cortisol concentrations before and at the end of exercise. A decrease in NA concentration was found already after 1 week of training at power output of 100 W (p<0.01) and 200 W (p<0.05). Similar decline was maintained after 3 weeks of training. No significant training-induced differences in plasma A concentration were found, however, the thresholds for both catecholamines were significantly shifted towards higher values after 3 weeks of training. One week of training caused a decrease in the pre-exercise (p<0.01), as well as post-exercise (p<0.05) plasma cortisol and HGH concentrations. It was concluded that endurance training induced a decrease in HGH, cortisol and NA concentration already after one week of training. A decline of pre-exercise plasma HGH and cortisol levels with time of experiment may, in part, indicate familiarization to exercise protocol.

Threshold for muscle lactate accumulation during progressive exercise.

The purpose of this study was to investigate the relationship between muscle and blood lactate concentrations during progressive exercise. Seven endurance-trained male college students performed three incremental bicycle ergometer exercise tests. The first two tests (tests I and II) were identical and consisted of 3-min stage durations with 2-min rest intervals and increased by 50-W increments until exhaustion. During these tests, blood was sampled from a hyperemized earlobe for lactate and pH measurement (and from an antecubital vein during test I), and the exercise intensities corresponding to the lactate threshold (LT), individual anaerobic threshold (IAT), and onset of blood lactate accumulation (OBLA) were determined. The test III was performed at predetermined work loads (50 W below OBLA, at OBLA, and 50 W above OBLA), with the same stage and rest interval durations of tests I and II. Muscle biopsies for lactate and pH determination were taken at rest and immediately after the completion of the three exercise intensities. Blood samples were drawn simultaneously with each biopsy. Muscle lactate concentrations increased abruptly at exercise intensities greater than the "below-OBLA" stage [50.5% maximal O2 uptake (VO2 max)] and resembled a threshold. An increase in blood lactate and [H+] also occurred at the below-OBLA stage; however, no significant change in muscle [H+] was observed. Muscle lactate concentrations were highly correlated to blood lactate (r = 0.91), and muscle-to-blood lactate ratios at below-OBLA, at-OBLA, and above-OBLA stages were 0.74, 0.63, 0.96, and 0.95, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of warm-up on muscle glycogenolysis during intense exercise.

This study investigated the effects of preliminary exercise (warm-up) on glycogen degradation and energy metabolism during intense cycle ergometer exercise. After determination of VO2max, six male subjects were randomly assigned to perform warm-up (WU) and no warm-up (NWU) trials incorporating a 2 min standardized sprint ride (SR) at 120% of the power output attained at VO2max (POmax). Muscle biopsies and temperature (Tm) recordings were obtained from the vastus lateralis muscle. Tm was elevated above the resting level prior to the SR during the WU trial (37.7 +/- 0.1 vs 35.4 +/- 0.4 degrees C; P less than 0.05) and remained higher than the NWU trial after the SR (38.6 +/- 0.2 vs 37.1 +/- 0.4 degrees C; P less than 0.05). Similar trends existed for rectal temperature (Tr). The increases in Tm and Tr during the SR were both greater in the NWU trial (P less than 0.05). Muscle glycogen degradation was similar for the WU and NWU trials (30.8 +/- 3.7 vs 25.6 +/- 3.7 mmol.kg-1, respectively). When blood and muscle lactate concentrations after the SR were expressed relative to values before the SR, the WU trial resulted in a lower accumulation of blood lactate (6.5 +/- 0.9 vs 10.7 +/- 0.8 mEq.l-1; P less than 0.01) and muscle lactate (20.1 +/- 0.1 vs 23.4 +/- 2.2 mEq.kg-1 wet wt.; P less than 0.05). Furthermore, oxygen consumption during the 1st min of the SR was higher in the WU trial (2.3 +/- 0.2 vs 1.9 +/- 0.2 l.min-1; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between EMG blood lactate, and plasma catecholamine thresholds during graded exercise in men.

The aim of this study was to follow up the electromyographic activity (EMG) of dynamically working muscles with simultaneous determinations of blood lactate and plasma catecholamine concentrations during progressive exercise. Twenty eight male soccer players aged 20.6 +/- 0.8 yrs performed incremental bicycle ergometer exercise test. The test consisted of 3-min stages exercise separated by 1-min rest intervals. Work load at each stage increased by 50 W until volitional exhaustion. The root mean square (rms)-EMG activity of the rectus femoris and soleus muscles were recorded continuously during exercise. Venous blood samples were taken after each exercise stage for determination of blood lactate (LA). Additionally in seven subjects adrenaline (A) and noradrenaline (NA) concentrations were determined. The EMG activity increased negligibly during exercise of low to moderate intensities revealing an abrupt rise at the load corresponding to thresholds of blood lactate and plasma catecholamine accumulation (LA-T, A-T, NA-T). Close correlations (P < 0.001) were found between blood LA concentration and EMG derived from rectus f. (r = 0.72) and soleus (r = 0.68) muscles. The mean threshold exercise intensities for m. rectus f. and m. soleus EMG (176 +/- 9 W and 172 +/- 9 W, respectively) did not differ significantly from lactate (164 +/- 7 W), noradrenaline (178 +/- 6 W) and adrenaline (180 +/- 5 W) thresholds, all of them detected by log-log transformation. The results indicate that threshold character of EMG changes in dynamically working muscles reflects to some extend the patterns of blood lactate and plasma catecholamine changes during incremental exercise.

Effect of phosphate supplementation on metabolic and neuroendocrine responses to exercise and oral glucose load in obese women during weight reduction.

Thirty six obese women (BMI 29.5 to 44.0 kg m-2, aged 27 to 45 yrs) participated in the 4- week weight reducing program. All of them have prescribed low fat diet of approx. 4.2 MJ (1000 kcal per day) with high viscous fibre capsules as a basic supplement. In addition 18 women (group 1) received Redusan mineral tablets containing mainly calcium and potassium phosphates while the remaining subjects (group 2) were given Placebo instead of mineral tablets. Before energy restriction and after 4 weeks on the diet, half of the women from each group performed 30 min--bicycle ergometer exercise (30-50 W; HR approx. 110 beats.min-1). The remaining subjects were submitted to oral glucose (75 g) tolerance test (OGTT). Weight loss during energy restriction was not affected by phosphate supplementation (4.6 +/- 0.4 and 5.2 +/- 0.5 kg in group 1 and 2, respectively). Phosphates caused a significant increase (p < 0.05) in the resting metabolic rate (RMR). Net energy cost of work, resting and post-exercise blood glucose, lactate, plasma FFA, adrenalin, cortisol, growth hormone, insulin and testosterone did not differ between the groups receiving phosphates and placebo while respiratory exchange ratio was slightly higher (p < 0.05), and the plasma beta-hydroxybutyrate concentration lower (p < 0.05) than without phosphate supplementation. Post-exercise plasma noradrenaline was significantly lowered after 4 weeks of energy restriction in group 2 (on Placebo). Neither blood glucose, plasma insulin and noradrenaline responses to oral glucose ingestion nor the glucose induced thermogenesis were significantly affected by phosphate supplementation, whilst blood pressure increases following glucose load were reduced (p < 0.05). In conclusion, the present study confirmed a potential usefulness of phosphate supplementation during energy restriction in obese patients due to its effect on resting metabolic rate. The results did not, however, reveal any major alterations in the metabolic and hormonal responses to exercise or to glucose ingestion in comparison with placebo treatment.

Effect of mild psychological stress on physiological responses to exercise in men.

UNLABELLED: To find out whether a negative shift in subject's mood alters cardio-respiratory and endocrine responses to exercise, 20 young men performed a graded bicycle ergometer test (50, 100, 150 W): 1) when they experienced a mixed emotional and cognitive stress before exercise (1st session), 2) when they were familiarized with the laboratory and rested quietly before exercise (2nd session). The subjects' mood was assessed by the Profile of Mood State (POMS) questionnaire. In the 1st session the subjects started exercise with significantly higher scores of tension, anger, depression, confusion and global mood in comparison with the 2-nd session. They also had slightly elevated systolic blood pressure, blood lactate, plasma cortisol and noradrenaline concentrations. During exercise performed in the 1st session only plasma free and total noradrenaline and cortisol levels were higher than those in the 2nd session. IN CONCLUSION: a mild psychological stress, causing the mood worsening before standard exercise test, does not evoke pronounced alterations in cardio-respiratory responses to exercise in healthy men, but it does affect the magnitude of exercise-induced changes in both plasma free and total noradrenaline concentrations.

Phosphate supplementation prevents a decrease of triiodothyronine and increases resting metabolic rate during low energy diet.

Thirty overweight women participated in 8 week slimming program consisting of a self-controlled low-energy diet (4.2 MJ/day) supplemented with highly viscous fibres and mineral tablets containing calcium, potassium and sodium phosphates (Redusan Combi, Biokraft Pharma AB, Sweden). Half of the patients received in double blind manner mineral tablets during first 4 weeks and placebo (without phosphates) during next 4 weeks (group 1) while the remaining patients were treated (cross-over) with placebo first and mineral tablets in the final period (group 2). The rate of weight loss was similar in groups 1 and 2 (4.7 vs 5.2 kg during the first 4 weeks and 2.7 vs 3.0 kg in the further 4 weeks). During periods of phosphate supplementation, the resting metabolic rate (RMR) increased by approx. 12% (p < 0.05) in group 1 and 19% (p < 0.05) in group 2. Phosphate supplementation ameliorated also a decrease in plasma triiodothyronine level and a decrease in thyroxine to triiodothyronine ratio. There were no differences between groups in the plasma insulin, catecholamine, growth hormone, cortisol and testosterone levels. Phosphate supplementation did not affect plasma lipids or blood glucose concentration. It is concluded that phosphate supplementation in obese patients on a low-energy diet enhances RMR irrespectively of the rate of weight loss. This effect seems to be, at least partly, due to an influence of phosphates on peripheral metabolism of thyroid hormones.

Early effects of short-term aerobic training. Physiological responses to graded exercise.

AIM: The aim of this study was to find out how early the moderate training effects appear and to check the hypothesis that familiarization with exercise protocol may contribute to an early physiological responses to training in previously sedentary subjects. METHODS: Twelve male, sedentary volunteers (22.0+/-0.7 yrs) were submitted to 3 weeks of a bicycle ergometer training, consisting of 45 min of exercise (at 70% VO(2)max), 3-4 times a week. The subjects performed 4 incremental exercise tests until volitional exhaustion: 2 before training (C1 and C2), and then after 1 (T1) and 3 (T3) weeks of training. During exercise HR, VO(2), electrical activity (EMG) of rectus femoris, biceps femoris, soleus and trapezius muscles were recorded and blood samples were taken for blood lactate (LA) determination. RESULTS: Already after 1 week of training HR decreased (p<0.05) with a further decline after 3 weeks the training (p<0.01). Maximal work load after 3 weeks of training increased to 277+/-10.4 W vs 250+/-9.5 W (p<0.05), VO(2)max achieved higher values than in C1 and C2 tests (p<0.05) and LA and EMG thresholds were elevated (p<0.05). CONCLUSION: A decrease in the resting and submaximal heart rate is the earliest effect of increased physical activity. Familiarization to exercise protocol decreased EMG of biceps femoris and soleus muscles during exercise, but did not influence that of rectus femoris muscle the most engaged during cycling.

Role of hepatic portal osmoreception in the control of ADH release.

Dogs were prepared for experiments by chronic implantation of catheters into the hepatic portal vein. Intraportal infusions of hypertonic saline, 5 ml/min, increased plasma antidiuretic hormones (rat bioassay) in absence of significant changes in systemic plasma osmolality. In the 5th min of 1.8, 2.7, or 3.6% saline infusion, plasma antidiuretic hormone (ADH) increased significantly from 3.2 +/- 0.7 to 14.3 +/- 3.6 (SE) microU/ml, from 2.3 +/- 0.4 to 42.0 +/- 7.6 microU/ml, and from 1.9 +/- 0.6 to 64.4 +/- 16.8 microU/ml, respectively. In control experiments plasma ADH did not change with isotonic saline infused intraportally or with 3.6% saline given into a systemic vein. The transsection of hepatic vagal afferent fibers abolished plasma ADH increase dependent on hypertonic intraportal infusion. The data support the existence of osmoreceptors within the portal vascular bed and indicate ADH involvement in the control of fluid balance by intrahepatic blood osmalality. The information on osmolality changes is neurally transmitted to the hypothalamus via hepatic vagal afferents. A demonstration of an increase in portal but not systemic blood osmolality following food intake suggests that intrahepatic osmoreception may be important in physiological regulation of water metabolism.

Effect of active warming-up on thermoregulatory, circulatory, and metabolic responses to incremental exercise in endurance-trained athletes.

The influence of 10 min warming-up at 40% VO2 max on thermal, circulatory, and metabolic responses to an incremental exercise to exhaustion as well as on the anaerobic threshold at the blood lactate level of 4 mmol.l-1 (AT) and the individual anaerobic threshold (IAT) was investigated in eight cross-country skiers. During exercise preceded by warming-up, the mean skin temperature (T sk) and external auditory canal temperature (Tac) did not change significantly in contrast to exercise without warming-up, producing a rise in both T sk and Tac (by approx. 1.2 degrees C and 1.1 degrees C, respectively). Warming-up did not alter the course of the rectal temperature changes during exercise. With warming-up skin humidity rose immediately after the beginning of exercise, whereas the onset of sweating without warming-up appeared much later at higher work intensities. Warming-up did not change the circulatory and ventilatory responses to incremental exercise and the oxygen uptake (VO2) either at submaximal or maximal work loads. With warming-up a significant increase was found in the threshold work load both at the AT and the IAT. The data demonstrated that warming-up has an advantageous effect on the efficiency of thermoregulation in endurance-trained athletes producing an early sweating response to the incremental exercise that results in attenuation of hyperthermia. An increase in the anaerobic threshold during incremental exercise preceded by warming-up may indicate an enhancement of the endurance capacity subsequent to warming-up.

Plasma noradrenaline response to sustained handgrip in patients with essential hypertension.

The responses of plasma noradrenaline, arterial blood pressure, and heart rate to sustained handgrip at 30% maximal voluntary contraction were studied in untreated patients with essential hypertension and in healthy subjects of comparable age. There were no significant differences between these two groups in the intensity and duration of handgrip. Increases in heart rate and blood pressure induced by the effort were similar in hypertensive patients and normotensive control subjects, whereas the absolute levels of blood pressure were considerably higher in the patients. In the first 1-2 min of exercise the increases in plasma noradrenaline concentration were similar in both groups. Subsequently, plasma noradrenaline concentration tended to plateau in hypertensive patients while in control subjects it continued to increase. The elevation of plasma noradrenaline in the last minute of effort was, therefore, significantly smaller in hypertensive patients than in the control group.

Plasma hormone and renal function changes in unrestrained dogs exposed to cold.

Renal clearances and plasma antidiuretic hormone (ADH), 17-hydroxycorticoids, and norepinephrine were measured in unrestrained dogs before and during exposure to ambient cold (minus 4 to + 4 degrees C). Some dogs were treated with an inhibitor of cortisol biosynthesis, Metopirone, either alone or combined with dexamethasone, a potent glucocorticoid suppressing ACTH release. Plasma ADH increased in the Metopirone-treated group (P smaller than 0.02) but changed little in other dogs. Plasma 17-hydroxycorticoids in untreated dogs rose from a control value of 14.4 plus or minus 1.9 (SE) to 1.82 plus or minus 1.2 mug/100 ml after 20 min of exposure (P smaller than 0.01), an increase comparable with that previously observed in restrained dogs. Plasma norepinephrine increased from 0.98 plus or minus 0.07 to 1.15 plus or minus 0.08 mug/liter (P smaller than 0.01) after 20 min of exposure. Urine flow, C-Cr, and C-PAH tended to increase spontaneously in nonexposed control dogs. Exposure to cold abolished or reversed this tendency, most distinctly in the Metopirone-dexamethasone group. The urine concentration, measured as T-c-H2O/C-Cr, did not change in cold, in contrast to a decrease previously observed in restrained dogs. The data do not support the key role of plasma cortisol elevation in the mechanism of urine-concentration defect in cold and demonstrate important differences between responses of restrained and unrestrained animals.

Adrenergic responses to sustained handgrip in patients with juvenile-onset-type diabetes mellitus.

1. The response of plasma noradrenaline, arterial blood pressure and heart rate to sustained handgrip at 30% of maximal voluntary contraction was studied in patients with long-term juvenile-onset-type diabetes millitus and healthy subjects of comparable age. 2. There was no significant difference between the intensity and duration of handgrip in diabetic patients and healthy subjects. 3. Sustained handgrip produced an increase in plasma concentration of noradrenaline both in diabetic and healthy subjects but the response in the diabetic subjects was significantly less. 4. The increase in systolic blood pressure during handgrip was significantly greater in diabetic subjects than in normal subjects. The increases in diastolic and mean blood pressure did not differ significantky. 5. The increase in heart rate during handgrip was greater in healthy subjects than in diabetic subjects. The response was smaller in diabetic patients with retinopathy than in the patients without retinopathy. 6. The sustained handgrip test may be useful for the diagnosis of abnormal sympathetic nervous system and haemodnynamic responsiveness in diabetic patients.

Renal function changes during preoptic-anterior hypothalamic heating in the rabbit.

Thermoregulatory reactions evoked by selective preoptic-anterior hypothalamic (PO/AH) heating in conscious rabbits were associated with significant changes in renal function. Urine flow rate decreased from a control value of 0.92 +/- (S.E.) 0.08 to 0.47 +/- 0.07 ml/min after 10-20 min of heating, urine osmolality increased from 273 +/- 34 to 417 +/- 46 Osm/kg H2O, and free water clearance per 100 ml GFR decreased from 1.11 +/- 0.46 to -0.50 +/- 0.23 ml/min. These changes were followed by a gradual recovery despite continued heating. Clearances of exogenous creatinine and p-aminohippurate fell transiently during the first 10 min of heating and then returned to normal. Plasma antidiuretic activity (ADA) measured by rat bioassay increased regularly and markedly during PO/AH heating but was poorly correlated with changes in urine concentration. Moreover, a similar increase in plasma ADA observed with selective heating of a different brain area (supraoptic nucleus) never produced urine concentration or other renal changes. This suggests that a large and variable fraction of ADA appearing in rabbit blood in response to thermal stimuli was not identical with antidiuretic hormone. Therefore, the causal relationship of ADH release and antidiuresis associated with thermoregulatory reactions could not be clearly demonstrated. The physiological role of renal water conservation would be to compensate for extrarenal water loss related to thermal sweating or panting.

ADH and thermal sweating.

Sweating responses to heat exposure were compared in healthy subjects pretreated with pitressin or alcohol and in the control group. Between the three groups, there were no consistent differences in the rate of sweating expressed both as a total body weight loss during 2-h heat exposure and in mg of sweat per skin area covered by a paper disc. Likewise, there were no differences in the sweat osmolality or electrolyte concentration. There was also no evidence of inverse correlation between plasma ADH level and rate of sweat secretion or its concentration when pooled data of all subjects were analyzed. It was concluded that ADH did not substantially affect thermal sweating in men.