The effects of chronic exercise on anesthesia induced hepatotoxicity.

UNLABELLED: A hypoxic rat model of halothane-induced hepatotoxicity, which is known to produce liver damage, was used to determine the effects of chronic exercise on halothane-induced hepatotoxicity and on reduced hepatic glutathione (GSH) levels. Metabolism of volatile anesthetics may generate metabolites that can cause mild and transient hepatotoxicity. METHODS: Six male Sprague-Dawley rats completed a 10-wk (5 d x wk(-1)) treadmill running protocol. Twelve age-matched animals were used as sedentary controls. After the completion of exercise training, rats were exposed for 2 h to 1% halothane in 14% O2. Twenty-four hours later, animals were anesthetized with sodium pentobarbital and sacrificed. Livers were excised, stained, and evaluated for hepatotoxicity using a histopathological 0 (normal) to 5 (severe damage) point categorical scale and for the determination of GSH levels. RESULTS: Median histopathologic scores revealed significantly lower indications of hepatotoxicity in exercise animals as compared with control animals (score = 0.25 vs 1.50; P < 0.05). Liver damages scores between 1 and 5 were observed in 75% (9 of 12) of the control animals, whereas only 1 of 6 exercise animals had a score greater than 1 (P < 0.05). No significant difference was observed in reduced GSH levels. CONCLUSIONS: Chronic exercise improves the detoxicant ability of the liver for halothane anesthesia as noted by the ameliorated liver damage and reduced incidence of halothane-induced hepatotoxicity in the exercise animals.

Decreasing activity limits for asthma patients.

Asthma disproportionally affects children, minorities, and people who live in urban areas ((1,2)) and is characterized by periodic episodes of wheezing, shortness of breath, tightness in the chest, increased mucus production in the lungs, and fatigue ((3,4)). Approximately 90% of all asthmatic patients experience exercise-induced asthma (EIA) that may develop slowly during exercise, with symptoms returning or intensifying during recovery ((4)).

Cardiovascular responses to beta-blockade and 5 degrees C cold air stress.

To determine the cardiovascular responses to beta-blockade and cold air stress, six males were randomly exposed at rest to three drug conditions (placebo, nonselective beta-blockade (propranolol), and selective beta-blockade (atenolol)) in each of two environments (5 and 25 degrees C) for 1 h. Cardiac output was lower on beta-blockade than on the placebo in both the 25 and 5 degrees C environments. Cardiac output on propranolol (4.2 +/- 0.3 L.min-1) at 5 degrees C was lower than on atenolol (4.7 +/- 0.4 L.min-1, p < 0.05). Mean arterial pressure was greater (p < 0.05) at 5 than 25 degrees C for each drug condition. There was no drug effect on total peripheral resistance at 25 degrees C. At 5 degrees C, total peripheral resistance on both beta-blockers (propranolol 1942.7 +/- 169.9 dyn.s.cm-5 (1 dyn = 10 microN); atenolol 1706.7 +/- 160.0 dyn.s.cm-5) was higher (p < 0.05) than on the placebo (1485.3 +/- 111.8 dyn.s.cm-5). Total peripheral resistance was also higher on propranolol than atenolol (p < 0.05). In conclusion, cold air stress interacts with beta-blockade to elevate total peripheral resistance by decreasing cardiac output while having little effect on mean arterial pressure. These effects are greater on nonselective than on selective blockade.

The energy cost of walking before and after significant weight loss.

The purpose of this study was to determine whether significant weight loss reduced the energy cost of activity more than that expected based on decreased body weight. Standing energy expenditure was measured and subtracted from the total energy cost of walking to determine ambulatory energy expenditure (AEE). The energy cost of walking was determined in 11 obese women at baseline, week 9 [after 8 wk of a 1758-3349 kJ.d-1 diet], and week 22 (after 2 wk of weight stability). AEE accounted for 80% of the energy cost of walking. Body weight was the principal determinant of AEE, but the relationship was not 1:1. Subjects reduced body weight by 13% at week 9 and 21% at week 22. Analyses which controlled for the relationship between AEE and weight at baseline, showed no change in AEE at week 9. By contrast, at week 22, AEE was reduced more than expected based on a lower body weight. These findings suggest that after significant weight loss, reduced-obese persons will expend less energy for the same activity, even after accounting for the decrease in body weight. These data also suggest that weight-based estimates of exercise energy expenditure may be inappropriate after significant weight loss.

Effects of caffeine or ethanol on treadmill performance and metabolic responses of well-trained men.

The effects of caffeine and ethanol on treadmill performance and metabolic responses to exercise were determined in four trained runners. Caffeine (2.5 mg.kg-1 body weight) or ethanol (25 ml) in 150 ml of grapefruit juice (total volume) or grapefruit juice (placebo) was randomly administered 10 minutes prior to and at 30 minutes of a 60 minutes treadmill run. The speed and grade of the treadmill was adjusted to elicit an average oxygen consumption of 80-85% of the subject's maximal oxygen consumption. All subjects completed the treadmill run for the caffeine and placebo conditions. Three of the four subjects could not complete the treadmill run following the second administration of ethanol. Exercise heart rate was significantly greater for the ethanol condition than for the placebo condition. Exercise oxygen consumption was greater following ethanol administration than for placebo, but the differences were not significant. Blood glucose rose significantly between 0 and 30 minutes of treadmill running for all three conditions. Between 30 minutes of treadmill running and either 60 minutes or the time of termination of the exercise, blood glucose decreased significantly by 24% following the second ethanol treatment. Plasma fatty acid, triglyceride, creatine phosphokinase, and renin contents followed expected exercise changes with a blunting of the rise of plasma fatty acids at 30 minutes of exercise for the ethanol condition. It was concluded that the administration of ethanol adversely influenced treadmill exercise performance by eliciting a hypoglycemic effect between 30 minutes and the termination of the exercise.

Effects of estradiol on lipoprotein lipase activity and lipid availability in exercised male rats.

The effects of 17 beta-estradiol 3-benzoate (10 micrograms.0.1 ml sunflower oil-1 x 100 g body wt-1) and exercise on tissue lipid content and lipoprotein lipase (LPL) activity were determined in male rats. Estradiol administration significantly (P < 0.05) increased fatty acid contents of resting adipose, plasma, and white and red vastus muscle tissues and red vastus muscle triacylglycerol. Adipose and plasma fatty acids and red and white vastus muscle triacylglycerol were significantly higher in exercised estradiol-administered animals than in exercised oil-administered animals. Estradiol administration significantly reduced resting adipocyte LPL activity by 71% and increased myocardial LPL activity by 96%. After exercise, red vastus LPL activity was significantly increased by 76% in estradiol-administered animals compared with oil-administered animals. Ratios of red vastus to adipose LPL activity and myocardial to adipose LPL activity at rest and after exercise were significantly greater in estradiol-administered than in oil-administered animals. Estradiol administration significantly increased the ratio of white vastus to adipose LPL activity of exercised animals. These data indicate that estradiol increases the availability of lipid substrate to exercising muscle from multiple sources, including adipose, plasma, and intracellular muscle triacylglycerol. The absolute increases in muscle LPL activity, combined with a greater ratio of muscle to adipose LPL activity, lead to increased distribution of plasma triacylglycerol-derived fatty acids toward muscle.

Exercise, aging, and nutrition.

Age-associated declines in resting energy expenditure and the thermogenesis of activity result in lower energy requirements in older adults. Regular aerobic exercise programs and strength or resistive training may increase the daily energy expenditure and/or may preserve or increase the lean body mass, which decreases with increasing age. Regular strength training exercise programs may improve bone mineral density and ambulation in older adults. Nutritional assessments suggest that older adults' protein intake should be at least 1 g per kilogram of body weight, and that calcium intake should be between 1,200 and 1,500 mg/day. Regular strenuous physical activity may require subtle changes in vitamin and mineral intake to compensate for loss of minerals in sweat and for exercise-induced increases in metabolism. Older adults may have a decreased thirst response to fluid deprivation. Fluid intake must be closely monitored with exercise activity to prevent dehydration.

Metabolic and nutritional considerations for exercising older adults.

Age-associated declines in REE and the thermogenesis of activity result in lower energy requirements in older adults. Regular aerobic exercise and resistive exercise programs will increase ones daily energy expenditure and may preserve or increase the lean body mass which has been shown to decrease with increasing age. Further, regular resistive exercise programs may improve bone mineral density and ambulation in older adults. Normal age-associated changes in gastrointestinal function and the addition of exercise may require some modification of nutrient intake. However, in the absence of gastrointestinal disease, these modifications should not be great for healthy sedentary older adults. Protein intake should be at least 1.0 g/kg body weight for older adults especially, physically active older adults.

Effect of estradiol on the temporal pattern of exercise-induced tissue glycogen depletion in male rats.

The effect of 17 beta-estradiol 3-benzoate (10 micrograms.01 ml of sunflower oil-1 x 100 g body wt-1) on the temporal pattern of exercise-induced tissue glycogen depletion and tissue lipid availability during submaximal treadmill running was determined in male rats. Animal were administered estradiol or oil for 5 days and were then time matched for motorized treadmill running for 30, 60, 90, or 120 min. Significant depletion of liver, soleus muscle, and red and white vastus lateralis muscle tissue glycogen occurred in oil-administered animals run between 30 and 120 min. The greatest extent of tissue glycogen depletion occurred during the first 30 min of exercise with the rate of glycogen depletion slowing between 30 and 120 min of exercise. Administration of estradiol attenuated the temporal pattern of glycogen depletion in both liver and muscle tissues. Significant depletion of red and white vastus glycogen of estradiol-administered animals did not occur until 90 and 120 min of exercise, respectively. Administration of estradiol significantly increased resting plasma free fatty acids and red and white vastus triacylglycerol content. These data indicate that estradiol administration for 5 days resulted in significant glycogen sparing of liver and muscle tissues during submaximal treadmill running for up to 120 min by altering the temporal pattern of glycogen depletion of male rats secondary to an estradiol-mediated increase in availability of lipid substrate during exercise.

Effect of ethanol on metabolic responses to treadmill running in well-trained men.

The metabolic effects of ethanol on treadmill performance were determined in four trained runners. Ethanol in doses of 25 mL in 150 mL of grapefruit juice (total volume) or grapefruit juice was randomly administered 10 minutes before and at 30 minutes of a 60-minute treadmill run. The speed and grade of the treadmill was adjusted to elicit an average oxygen consumption (VO2) of 80 to 85% of the subjects' VO2max. Three of the four subjects could not complete the treadmill run after the administration of ethanol. Administration of ethanol resulted in significant increases in the heart rate responses to treadmill running above those for the placebo grapefruit treatment. VO2 was higher after ethanol administration than the placebo grapefruit juice treatment, but these values were not significant. Blood glucose content rose significantly between 0 and 30 minutes of treadmill running for both the ethanol and placebo grapefruit juice treatments. Between 30 minutes of treadmill running and the termination of the exercise, the blood glucose level decreased significantly by 24% after the second ethanol treatment at 30 minutes of exercise. Plasma fatty acid, triglyceride, creatine phosphokinase, and renin contents followed expected exercise changes. It was concluded that the administration of ethanol adversely influenced treadmill exercise performance by eliciting a hypoglycemic effect between 30 minutes and the termination of the exercise.

Effect of estradiol on tissue glycogen metabolism and lipid availability in exercised male rats.

The effect of 17 beta-estradiol 3-benzoate (10 micrograms.0.1 ml sunflower oil-1.100 g body wt-1) on exercise performance, tissue glycogen utilization, and lipid availability was determined in male rats. In experiment 1, estradiol or oil was administered 1 h or 1-6 days before a treadmill run to exhaustion. No differences in body weight between oil- and estradiol-administered animals were observed during the 6-day treatment. Animals receiving estradiol for 3-6 days ran significantly longer and completed more work than oil-administered animals. Significant degradation of red and white vastus muscle, myocardial, and liver glycogen was observed in all animals run to exhaustion. In experiment 2, animals were administered estradiol for 5 days and then run for 2 h. The submaximal run for 2 h significantly reduced tissue glycogen content in red and white vastus muscle, heart, and liver of oil-administered animals. The latter effect was attenuated in both vastus muscles, liver, and myocardial tissues in the estradiol-administered animals. Estradiol administration significantly increased plasma fatty acids and lowered plasma lactate during the submaximal run. These data indicate that when body weight remained constant between groups of male rats, estradiol administration for 3-6 days increased exercise performance. Furthermore, estradiol administration for 5 days resulted in greater lipid availability and less tissue glycogen utilization during submaximal running for 2 h.

Reassessment of body mass indices.

The accuracy of body mass indices (BMIs), such as Quetelet's index, for the definition of obesity was investigated in a large sample of healthy humans. Two hundred thirteen women and 150 men with a wide spectrum of weights, heights, and ages underwent densitometric analysis for the determination of percent body fat (%BF). %BF was then contrasted with various well-established BMIs. Although %BF was correlated with all the BMIs (r = 0.60-0.82), applying objective definitions of obesity based on BMIs or %BF by densitometry often produced conflicting results. It was also found that the 95% confidence intervals for predicting %BF by using Quetelet's index were very wide. Because of the wide variation for individuals between densitometrically determined body fat and body fat as estimated by BMIs, we conclude that BMIs should be used with caution as indicators of obesity.

Resting metabolic rate and body composition of achondroplastic dwarfs.

Indirect calorimetry was used to measure resting metabolic rates (RMR), and densitometry and anthropometry were used to measure body fat and fat-free masses of 32 adults with very short stature. Twenty-seven of them were achondroplastic dwarfs. Their results were compared to those obtained from 103 lean and obese adults with normal heights. All 32 dwarfs had distinctly greater RMR per kg fat-free mass by densitometry than adults with average stature. However, there was a wide variation in the RMR among dwarfs, which was independent of leanness or obesity. In spite of increased RMR, obesity among dysplastic adult dwarfs was twice as prevalent as among average-height adults. Increased abdominal:hip ratios were prevalent among dwarfs, but these ratios do not reflect body fat. Body mass indices were worthless, and skinfold thicknesses and other anthropometric measurements were of very limited value in predicting the body fat of dwarfs. Although our new and specific equations for estimating RMR and body composition give reasonable values, we recommend that the caloric requirements and body compositional variables be measured if nutritional therapy is needed to induce weight loss or gain in Little People.

Thermic effect of food in lean and obese men.

A systemic reappraisal of the thermic effect of food was done in lean and obese males randomly fed mixed meals containing 0, 8, 16, 24, and 32 kcal/kg fat-free mass. Densitometric analysis was used to measure body composition. Preprandial and postprandial energy expenditures were measured by indirect calorimetry. The data show that the thermic effect of food was linearly correlated with caloric intake, and that the magnitude and duration of augmented postprandial thermogenesis increased linearly with caloric consumption. Postprandial energy expenditures over resting metabolic requirements were indistinguishable when comparing lean and obese men for a given caloric intake. Individuals, however, had distinct and consistent thermic responses to progressively greater caloric challenges. These unique thermic profiles to food ingestion were also independent of leanness or obesity. We conclude that the thermic effect of food increases linearly with caloric intake, and is independent of leanness and obesity.

Effect of estradiol on tissue glycogen metabolism in exercised oophorectomized rats.

The effect of both physiological and pharmacological doses of estradiol on exercise performance and tissue glycogen utilization was determined in oophorectomized estradiol-replaced (ER) rats. Doses of beta-estradiol 3-benzoate (0.02, 0.04, 0.1, 0.2, 1, 2, 4, or 10 micrograms.0.1 ml of sunflower oil-1.100 g body wt-1) were injected 5 days/wk for 4 wk. Controls were sham injected (SI). After treatment, the animals were run to exhaustion on a motorized treadmill. ER animals receiving the 0.02-microgram dose ran significantly longer and completed more total work than the SI group. ER animals receiving doses of greater than or equal to 0.04 microgram ran longer and performed more work than the 0.02-microgram group. At exhaustion, myocardial glycogen content was significantly decreased in animals that were ER with less than or equal to 0.1 microgram, whereas those replaced with doses greater than 0.1 microgram utilized significantly less glycogen. With the 10-micrograms dose no significant decrease in heart glycogen content was observed at exhaustion. A submaximal 2-h run significantly reduced glycogen content in heart, red and white portions of the vastus lateralis, and the livers of SI animals. The latter effect was attenuated in skeletal muscle and liver, and there was no effect in the hearts of the ER animals receiving 2 micrograms. These data indicate that estradiol replacement in oophorectomized rats influenced myocardial glycogen utilization during exhaustive exercise and spared tissue glycogen during submaximal exercise. These glycogen sparing effects may have contributed to the significant improvements in exercise performance observed in this study.

Cardiovascular drugs and exercise interactions.

An appreciation of the hemodynamic and biochemical changes induced by drugs is critical for a logical diagnostic interpretation of graded stress tests and the evaluation of the projected exercise prescription and exercise programs that a patient is asked to follow. Drug therapy is clearly not a contraindication to acute or chronic exercise as long as the potential benefits and complications of exercise and drug interaction are considered.

The effect of pantothenate deficiency in mice on their metabolic response to fast and exercise.

The changes in fuel metabolism during fast and exercise were compared to the tissue total CoA levels in mice maintained on pantothenate-deficient and pantothenate-supplemented (control) diets. In nonexercised mice maintained on a pantothenate-deficient diet for 65 to 105 days, the total CoA levels of many tissues were significantly lower than in controls (liver 18%, kidney 23%, spleen 21%, heart 38%, and leg skeletal muscle 66%). However, no differences in total CoA levels in brain or epididymal fat pads were observed. During a 48-hour fast, the total CoA levels increased in the heart and liver of both pantothenate-deficient and control mice (heart 32 and 19%, respectively; liver 39 and 45%, respectively), but the level of total CoA remained lower in the deficient mice. Liver glycogen levels were 17% lower in deficient mice than in controls and liver ketone bodies were 17% higher in pantothenate deficient mice than in controls. Separate groups of mice on deficient and supplemented diets were trained to run to exhaustion. Compared to trained mice on pantothenate-supplemented diets, the trained pantothenate-deficient mice had lower running times until exhaustion, lower body weights, lower liver and muscle glycogen content (even after rest), and elevated liver ketone bodies both during rest and after running. In summary, the pantothenate-deficient mice were unable to maintain normal glycogen stores, but had a normal ketogenic response to fast and exercise in spite of the lower levels of liver total CoA.

Bioenergetics in the aging Fischer 344 rat: effects of exercise and food restriction.

The capacity for energy production was evaluated in male, Fischer 344 rats as they advanced from adulthood through senescence. At 10 months of age, the animals were divided into three groups: sedentary, fed ad libitum (S); exercised by treadmill running, fed ad libitum (E); and sedentary, caloric restricted by alternate day feeding (R). Activities of selected enzymes, ADP-stimulated respiration and levels of cytochromes, were determined in homogenates of liver and gastrocnemius muscle prepared from young controls (10-month old S) and 18-, 24-, and 30-month old animals. In liver, age-linked decrements were found in the activities of 3-hydroxyacyl-CoA dehydrogenase (S, E, and R) and citrate synthase (S), and in cytochrome c content (S and E), whereas substrate-catalysed oxidations were unaffected. In the gastrocnemius muscle (S, E, and R), respiration, activities of enzymes of the Krebs cycle and glycolysis, and cytochrome content were decreased after the age of 18 months. Oxidative capacity was increased in muscle through exercise (about 40%) and in liver by food restriction (about 20%). Body and soleus muscle mass declined similarly in all groups (about 14% from 30 to 18 months of age), whereas the loss of weight in the gastrocnemius muscle was much greater (34%). The data indicate that energy metabolism in the senescent animal is competent to meet its needs and age-related declines in energy metabolism are secondary to the aging process.

A reappraisal of caloric requirements in healthy women.

The caloric expenditure of 44 healthy, lean and obese women, 8 of whom were trained athletes, was measured by indirect calorimetry. Body composition was determined. Ages ranged from 18-65 yr and body weights from 43-143 kg. Stepwise, multiple-regression analysis was used to determine whether one or several variables best predicted the resting metabolic rate (RMR) of the women. The RMR and the thermic effect of food (TEF) were measured before and after the women consumed a mixed breakfast meal. The results showed that the currently available tables and regression equations overestimate the RMR of healthy women by 7-14%. Body weight was highly related to the RMR, and stepwise inclusions of various variables did not improve predictions of RMR. The slopes of the regression lines for nonathletes and athletes were significantly different. Regression equations for predicting RMR of women were developed: Nonathletes RMR = 795 + 7.18 kg WT; Athletes RMR = 50.4 + 21.1 kg WT. The range of RMR per kilogram body weight was wide for nonathletic, but narrow for athletic women. The metabolism of some lean and obese, nonathletic women was highly efficient, predisposing these women for developing and maintaining body fat. The TEFs were indistinguishable between nonathletic and athletic women, and formed a continuum from the lightest to the heaviest woman.