Ronald D. Fell

Body Fat and the Activity of the Autonomic Nervous System

The cause of most cases of human obesity is unknown. Specific alterations in the activity of the autonomic nervous system may mediate and perhaps cause obesity in animal models. We therefore looked for alterations in autonomic activity in human obesity. Fifty-six healthy men with various percentages of body fat underwent autonomic testing while at rest. Significant correlations were found between the percentage of body fat and the variation in the R-R interval after beta-adrenergic blockade (r = -0.30, P less than 0.03), the heart rate (r = 0.30, P less than 0.03), the plasma norepinephrine concentration (r = -0.30, P less than 0.05), the plasma epinephrine concentration (r = -0.49, P less than 0.001), and the pupillary latency period (r = 0.39, P less than 0.01). Each of these variables reflects the activity of the sympathetic nervous system or parasympathetic nervous system or both. Depressions in sympathetic and parasympathetic activity were significantly but weakly associated with increasing percentages of body fat. These associations indicate that in obese persons, autonomic changes, though not necessarily causal, involve several organ systems. We suggest that autonomic alterations are important in human obesity, as they are in animal obesity. A disordered homeostatic mechanism may promote excessive storage of energy by decreasing sympathetic activity, while defending against weight gain by decreasing parasympathetic activity. The use of autonomic profiles holds promise for classifying human obesity and identifying obese patients at increased risk for various disorders.

Autonomic influence on cardiovascular performance in diabetic subjects

PURPOSE Cardiomyopathy, coronary artery atherosclerosis, or autonomic neuropathy may affect the cardiovascular performance of the diabetic patient. To evaluate the role of parasympathetic nervous system activity on cardiovascular performance, 25 diabetic subjects who lacked symptoms, signs, or objective measurements of ischemia or cardiomyopathy were studied. PATIENTS AND METHODS Diabetic subjects were classified according to their RR variation, an index of cardiac parasympathetic nervous system activity. Fourteen diabetic subjects had a normal RR variation of greater than 30 (D-NOR), and 11 diabetic patients had an abnormal RR variation of less than 20 (D-ABN). Fifteen age- and weight-matched, healthy, nondiabetic subjects (NOR) constituted the control group. All subjects had oxygen consumption, multigated acquisition determination of cardiac output, and work product measured before and during supine bicycle maximum exercise testing. RESULTS There was no difference in the resting cardiac output among the groups. Resting work product, however, was greatest in the D-ABN group when compared with performance in the other two groups (D-ABN: 11,500 +/- 800; D-NOR: 9,000 +/- 600; NOR: 8,700 +/- 400; p less than 0.0025). This was due to an increase in both heart rate (p less than 0.025) and systolic blood pressure (p less than 0.015). In the diabetic subjects, there was an inverse relationship between the RR variation and resting work product (r = 0.47, n = 25, p less than 0.005). In response to exercise, the percent increase in cardiac output at matched percent maximum oxygen uptake was greatest in the NOR, D-NOR, and D-ABN groups, respectively (analysis of variance, p less than 0.01). In the diabetic subjects, there was a significant relationship between the RR variation and the maximum percent change in cardiac output (r = 0.41, n = 25, p less than 0.02). Compared with the NOR group, the maximum increase in work product was impaired in diabetic subjects (p less than 0.002) and not different between the D-NOR and D-ABN groups. CONCLUSIONS The increase in resting work product and the poor cardiac output responses to exercise in the D-ABN group are due to a decrease in cardiac parasympathetic nervous system activity and can be suggested by an abnormal RR variation. This index of parasympathetic nervous system activity can help the physician identify that subset of diabetic patients that may need special consideration when exercise training is prescribed.

TRANSLOCATION OF TWO GLUCOSE TRANSPORTERS IN HEART : EFFECTS OF ROTENONE, UNCOUPLERS, WORKLOAD, PALMITATE, INSULIN AND ANOXIA

Our previous studies on the acute regulation of glucose transport in perfused rat hearts were extended to explore further the mechanism of regulation by anoxia; to test the effects of palmitate, a transport inhibitor; and to compare the translocation of two glucose transporter isoforms (GLUT1 and GLUT4). Following heart perfusions under various conditions, glucose transporters in intracellular membranes were quantitated by reconstitution of transport activity and by Western blotting. Rotenone stimulated glucose uptake and decreased the intracellular contents of glucose transporters. This indicates that it activates glucose transport via net outward translocation, similarly to anoxia. However, two uncouplers of oxidative phosphorylation produced little or no effect. Increased workload (which stimulates glucose transport) reduced the intracellular contents of transporters, while palmitate increased the contents, indicating that these factors cause net translocation from or to the intracellular pool, respectively. Relative changes in GLUT1 were similar to those in GLUT4 for most factors tested. A plot of changes in total intracellular transporter content vs. changes in glucose uptake was roughly linear, with a slope of -0.18. This indicates that translocation accounts for most of the changes in glucose transport, and the basal pool of intracellular transporters is five times as large as the plasma membrane pool.

Cigarette smoking, physical activity, and alcohol consumption: Relationship to blood lipids and lipoproteins in premenopausal females

A total of 164 premenopausal female subjects were randomly selected for evaluation from a much larger pool of volunteers. The relationships between blood lipid and lipoprotein levels as dependent variables and cigarette smoking, physical activity, and alcohol consumption were determined from partial regression coefficients. A lower HDL-C level (10.1 mg/dL) was seen in smokers v nonsmokers. For each ounce of alcohol consumed, HDL-C level was higher by 2.8 mg/dL, and greater physical activity was associated with a higher HDL-C level of 8.6 mg/dL. An analysis of covariance with covariance adjustments for age and body fat revealed that smokers who regularly exercise or consume alcohol had significantly lower HDL-C levels than nonsmokers with similar habits. Subjects who both exercise and consume alcohol demonstrated higher HDL-C levels than those who indulge in one or the other separately. Results suggest that cigarette smoking may attenuate the effects of chronic exercise or alcohol consumption, or of both, to raise HDL-C levels. Also, chronic exercise and alcohol consumption may exert an additive effect, raising HDL-C level.

Cigarette smoking, exercise and high density lipoprotein cholesterol

Cigarette smoking is associated with depressed levels of HDL-C, whereas exercise is associated with elevated levels of HDL-C. The purpose was to determine effects of smoking and exercise on blood lipids and lipoproteins in middle-aged males. It was hypothesized that smoking may attenuate the effects of exercise to elevate HDL-C. A total of 269 males (70 smokers) met all criteria for inclusion in the study population. Age, height, weight, body fatness via hydrostatic weighing, daily caloric consumption and alcohol intake, and smoking habits and history were determined. Interviews concerning physical activity patterns were conducted and cardiovascular responses to treadmill exercise were determined. Subjects were grouped as sedentary (low activity), participants in vigorous recreational activities (moderate activity) and joggers/runners (high activity). Analysis of covariance with adjustments for factors which may affect blood lipids and lipoproteins was employed. Smokers demonstrated lower HDL-C and higher total cholesterol levels than nonsmokers. High activity subjects demonstrated significantly higher HDL-C levels than the low and moderate groups which did not differ. High activity smokers did not differ from low activity nonsmokers with respect to HDL-C. This supports the proposed hypothesis. Nonsmokers were higher in weight and body fatness than smokers even though smokers consumed 288 more calories per day on the average. This suggests that smoking may account for a significant number of calories through altered metabolism or some other means.

The effect of an aldose reductase inhibitor on cardiovascular performance in patients with diabetes mellitus

Because some aldose reductase inhibitor studies have demonstrated clinical improvement in scored neurological signs and symptoms of diabetic neuropathy, a prospective study of the effect on cardiovascular performance of sorbinil 250 mg/day for 12 months was conducted on patients with diabetic autonomic neuropathy who were free of atherosclerotic coronary artery disease and/or cardiomyopathy. After 1 year of treatment, the study group (n = 14) demonstrated significant improvement in both the resting cardiac output (P = 0.02), and the maximal cardiac output (P = 0.03). This observation suggests that the use of an aldose reductase inhibitor may be useful in treating suboptimal cardiovascular performance in patients with diabetic cardiac autonomic neuropathy.

Respiratory alkalosis: no effect on blood lactate decline or exercise performance

SummaryIt was the purpose of this study to determine the effects of respiratory alkalosis before and after high intensity exercise on recovery blood lactate concentration. Five subjects were studied under three different acid-base conditions before and after 45 s of maximal effort exercise: 1) hyperventilating room air before exercise (Respiratory Alkalosis Before=RALB, 2) hyperventilating room air during recovery (Respiratory Alkalosis After=RALA), and 3) breathing room air normally throughout rest and recovery (Control =C). RALB increased blood pH during rest to 7.65±0.03 while RALA increased blood pH to 7.57±0.03 by 40 min of recovery. Neither alkalosis treatment had a significant effect on blood lactate concentration during recovery. The peak lactate values of 12.3±1.2 mmol · L−1 for C, 11.8±1.2 mmol · L−1 for RALB, and 10.2±0.9 mmol · L−1 for RALA were not significantly different, nor were the half-times (t1/2) for the decline in blood lactate concentration; C=18.2 min, RALB=19.3 min, and RALA=18.2 min. In C, RALB and RALA, the change in base excess from rest to postexercise was greater than the concomitant increase in blood lactate concentration, suggesting the presence of a significant amount of acid in the blood in addition to lactic acid. There was no significant difference in either the total number of cycle revolutions (C=77±2, RALB=77±1) or power output at 5 s intervals between RALB and C during the 45 s. These results suggest that the possible range of respiratory alkalosis changes in intact humans may be insufficient 1) to affect recovery blood lactate concentrations, or 2) to affect intense, short-term exercise performance.

Effects of acute smoking and exercise on high-density lipoprotein-cholesterol and subfractions in black female smokers☆

This study investigated the effects of acute bouts of both exercise and smoking on high-density lipoprotein-cholesterol subfractions, HDL2-C and HDL3-C in black females. During two testing trials, seven subjects were exposed to either acute exercise or smoking. Treadmill exercise was performed at 70% of heart rate reserve for 15 minutes. Blood samples were taken before, immediately after, and 10 minutes after exercise. The smoking trial consisted of subjects smoking two cigarettes followed by 30 minutes of nonsmoking. Blood samples were taken before smoking, after each cigarette, and after two 15-minute intervals of nonsmoking. The exercise protocol resulted in a 10.8% increase in total HDL-C, primarily through an increase in the HDL2-C subfraction. The values returned to baseline within 10 minutes after exercise. Smoking one cigarette decreased total HDL-C by 10%. Neither subfraction was significantly effected by smoking; however, the HDL3-C subfraction was decreased 11% and HDL2-C subfraction was decreased 14.7% from resting values. The maximum reduction in HDL3-C subfraction occurred after the smoking of the first cigarette, while the maximum reduction in the HDL2-C subfraction occurred after the first 15-minute nonsmoking period. Acute cigarette smoking was associated with a decrease in total HDL-C that was maintained through 15 minutes of nonsmoking. It is suggested that the adverse effect on HDL-C by acute smoking is a significant contributor to coronary heart disease (CHD) risk in black females. Results further indicate that low-intensity exercise is capable of transiently increasing the total HDL-C via an increase in the anti-atherogenic HDL2-C subfraction.(ABSTRACT TRUNCATED AT 250 WORDS)