Mild combined immunodeficiency in identical twins

Fourteen adult cats were exercised on a motor-driven treadmill 5 days each week for 6 weeks to determine the effect of exercise conditioning on the intrinsic contractile state of the myocardium. The exercise program was sufficient to produce a cardiovascular training effect manifested by slower exercising heart rates and resting heart rates after atropine by the end of the 6th week. The mechanical function of the isolated right ventricular papillary muscle from exercised cats was compared with that of 17 sedentary adult cats. There were no significant differences between exercised and control cats in in heart weight-body weight ratios, resting and active lenght - tension relations, maximal rate of isometric force development at the peak of the length-tension curve (Lmax), time to peak force at Lmax, maximal force development with paired stimulation and norepinephrine, or force-velocity relations. These results indicate that the intrinsic state of feline myocardium is unaffected by exercise conditioning.     

P-R interval in relation to heart rate during exercise and the influence of posture and autonomic tone

P-R interval (PR) in relation to heart rate (HR) during exercise was studied in healthy men. When subjects were in a recumbent position, mean PR between HR 90-140 beats/min (bpm) decreased linearly from 167 +/- 8 ms to 136 +/- 5 ms. (Regression line: PR = 0.287 HR + 182.9, r = 0.40). PR did not decrease further at HR up to 180 bpm. When subjects were in a sitting position, a further decrease occurred after HR 150-160 bpm. The shortest PR observed during exercise was 100 ms. The decrease of PR between HR 90-140 bpm was affected by atropine but not by propranolol. Higher HR was not achieved after propranolol, and after atropine there was no difference in PR in either exercise position compared to the two exercises without any drug. Thus, exercise induces a decrease in PR which is for the most part completed at HR 140-150 bpm and is mainly achieved by a withdrawal of the parasympathetic tone. PR at HR 90 bpm was correlated to body surface area, indicating that the PR duration is related to the body and heart dimensions.     

Reduction of intrinsic sinoatrial frequency and norepinephrine response of the exercised rat

Physical training is associated with a reduction of intrinsic sinoatrial activity; the present study examined the role of the parasympathetic nervous system in this reduction. Six groups of rats were studied for 10 weeks: inactive control; treadmill exercised; parasympathetic receptor blockade with atropine; exercise plus atropine; parasympathetic receptor stimulation with carbachol; and exercise plus carbachol. In vivo ISF (cardiac frequency 20 min after injection of propranolol and atropine) was measured at 3-week intervals. At the end of 10 weeks the right atrium was excised, in vitro measurements were made of ISF, and chronotropic dose-response curves to acetylcholine and norepinephrine were established. In vivo, ISF was reduced with time, the greatest reduction being found in the exercise plus atropine group; the treadmill-exercised and the atropine-treated groups also had a greater reduction than the control group. In vitro, no differences were observed in acetylcholine responses. The maximum norepinephrine chronotropic response was reduced in the treadmill-exercised and the exercise plus atropine groups. The maximum norepinephrine-induced frequency correlated with the in vitro ISF (r = 0.75). Thus, ISF was reduced with training, but this effect was independent of parasympathetic activity. The properties of the sinoatrial node which set ISF also influenced the maximum norepinephrine response.     

Sarcoidosis and cancer revisited: a long-term follow-up study of 555 Danish sarcoidosis patients

STUDY OBJECTIVE: To determine whether an aerobic endurance training program (AET) in comparison to normal daily activities improves exercise capacity in lung transplant recipients. PATIENTS AND STUDY DESIGN: Nine lung transplant recipients (12+/-6 months after transplant) were examined. All patients underwent incremental bicycle ergometry with the work rate increased in increments of 20 W every 3 min. Identical exercise tests were performed after 11+/-5 weeks of normal daily activities and then after a 6-week AET. The weekly aerobic training time increased from 60 min at the beginning to 120 min during the last week. Training intensity ranged from 30 to 60% of the maximum heart rate reserve. RESULTS: Normal daily activities had no effect on exercise performance. The AET induced a significant decrease in resting minute ventilation from 14+/-5 to 11+/-3 L/min. At an identical, submaximal level of exercise, a significant decrease in minute ventilation from 47+/-14 L/min to 39+/-13 L/min and heart rate from 144+/-12 to 133+/-17 beats/min, before and after the AET, was noted. The increase in peak oxygen uptake after AET was statistically significant (1.13+/-0.32 to 1.26+/-0.27 L/min). CONCLUSIONS: These data demonstrate that normal daily activities do not affect exercise performance in lung transplant recipients > or = 6 months after lung transplantation. An AET improves submaximal and peak exercise performance significantly.     

Perioperative growth hormone treatment increases nitrogen and fluid balance and results in short-term and long-term conservation of lean tissue mass

STUDY OBJECTIVE: To evaluate changes due to pregnancy on atenolol's pharmacokinetics, response of maternal heart rate to atenolol, and the drug's effect on fetal heart rate. DESIGN: Prospective study. SETTING: Large university teaching hospital. PATIENTS: Fourteen pregnant women who were receiving oral atenolol for cardiac disease were enrolled and 10 completed the study. INTERVENTIONS: Patients were studied for 12 hours during the third trimester (TT) and again 6 weeks postpartum (PP). MEASUREMENTS AND MAIN RESULTS: Fetal heart rates, and maternal heart rates at rest and during exercise were recorded. Maternal plasma and urine atenolol concentrations were measured. Average resting heart rates (TT 68+/-10, PP 62+/-9 beats/min) and maximum heart rate during exercise (TT 100+/-6, PP 87+/-7 beats/min) were significantly higher in the third trimester than postpartum (p<0.05). The 12-hour atenolol area under the curve (TT 0.208+/-0.061, PP 0.215+/-0.089 ng/ml/day) and maximum plasma concentrations during the time of exercise tests (TT 1.07+/-0.39, PP 1.14+/-0.53 mmol/L) were not significantly different. Individual and population pharmacokinetics did not differ significantly between study periods. The fetal heart rate did not correlate with maternal atenolol concentration. CONCLUSION: Constant dosages of atenolol result in higher heart rates during pregnancy compared with the postpartum period. This lack of heart rate control is not due to significant changes in atenolol's pharmacokinetics or plasma concentrations.     

A comparative study of activity and dual sensor: activity and minute ventilation pacing responses to ascending and descending stairs

Previous studies with activity-based rate adaptive pacemakers have shown a somewhat paradoxical response when comparing ascending stairs to descending stairs. The objective of this investigation was to measure dual-sensor rate response provided by activity and minute ventilation (MV) compared with activity alone, and with a control group, during ascending and descending stairs. For dual sensor mode, measured mean peak pacing rate with 72 (92) steps per minute was 111 +/- 13 beats/min (124 +/- 14 beats/min) ascending stairs and 81 +/- 7 beats/min (97 +/- 13 beats/min) for descending. For activity mode alone, mean peak pacing rate was 90 +/- 12 beats/min (108 +/- 19 beats/min) ascending stairs and 97 +/- 12 beats/min (123 +/- 17 beats/min) descending. The mean peak control group heart rate ascending stairs for a step rate of 72 (92) steps/min were 116 +/- 11 beats/min (127 +/- 14 beats/min) ascending stairs and for descending 89 +/- 12 beats/min (95 +/- 11 beats/min). While for dual sensor controlled pacing there was a significant difference for ascending and descending stairs at both step rates, there was no difference between going upstairs and downstairs for activity mode alone. Rates with dual sensor did not significantly differ from respective rates of the control group. The mean correlation coefficient between MV and paced rate was 0.85. Pacing heart rates delivered by the dual sensor mode were appropriate for ascending and descending stairs. In contrast to activity mode alone, the peak heart rates for dual sensor mode are higher during ascending than during descending stairs.     

Effect of endurance exercise training on heart rate variability at rest in healthy young and older men

Heart rate variability (HRV) (SD of the RR interval), an index of parasympathetic tone, was measured at rest and during exercise in 13 healthy older men (age 60 to 82 years) and 11 healthy young men (age 24 to 32 years) before and after 6 months of aerobic exercise training. Before exercise training, the older subjects had a 47% lower HRV at rest compared with the young subjects (31 +/- 5 ms vs 58 +/- 4 ms, p = 0.0002). During peak exercise, the older subjects had less parasympathetic withdrawal than the young subjects (-45% vs -84%, p = 0.0001). Six months of intensive aerobic exercise training increased maximum oxygen consumption by 21% in the older group and 17% in the young group (analysis of variance: overall training effect, p = 0.0001; training effect in young vs old, p = NS). Training decreased the heart rate at rest in both the older (-9 beats/min) and the young groups (-5 beats/min, before vs after, p = 0.0001). Exercise training increased HRV at rest (p = 0.009) by 68% in the older subjects (31 +/- 5 ms to 52 +/- 8 ms) and by 17% in the young subjects (58 +/- 4 ms to 68 +/- 6 ms). Exercise training increases parasympathetic tone at rest in both the healthy older and young men, which may contribute to the reduction in mortality associated with regular exercise.     

Managed primary care of nursing home residents

The mechanisms responsible for immediate adjustments in cardiac output at onset of exercise, in the absence of neural drive, are not well defined in heart transplant (HT) recipients. Seven male HT recipients (mean +/- SD 57 +/- 6 years) and 7 age-matched sedentary normal control subjects (mean age 57 +/- 5 years) performed constant load cycle exercise at 40% of peak power output (Watts). Cardiac output and plasma norepinephrine were determined at rest and every 30 seconds during the first 5 minutes of exercise and at minutes 6, 8, and 10. All subjects were admitted to the General Clinical Research Center for determination of plasma volume. After 3 days of equilibration to a controlled and standardized diet, plasma volume was measured using a modified Evans Blue Dye (T-1824) dilution technique. Heart rate at rest was higher in the HT group (105 +/- 12 vs 74 +/- 6 beats/min), but during submaximum exercise, heart rates in the control group increased more rapidly (p < or = 0.05) and to a greater magnitude (54 +/- 7% vs 17 +/- 4% above rest). Stroke volume at rest was lower in HT recipients (45 +/- 4 vs 68 +/- 9 ml) but was significantly augmented immediately after onset of exercise (30 seconds) and the relative increase was greater than controls at peak exercise (61% vs 38% greater than baseline). Cardiac output at rest was within the normal range in both groups (4.58 +/- 0.27 vs 4.94 +/- 0.40 L/min). Relative increases in cardiac output were similar (p > or = 0.05) for the HT (106 +/- 12%) and control groups (97 +/- 10%). Plasma norepinephrine did not become significantly greater than resting values until approximately 4 minutes after onset of exercise in both groups. Blood volume, normalized for body weight, was 12% greater in the HT group. Thus, HT recipients with expanded blood volume (12%) augment stroke volume immediately after the onset of exercise. Plasma norepinephrine levels contribute negligibly to the rapid adjustment in cardiac output. Rather, we speculate that abrupt on-transit increases in stroke volume are due to augmented venous return, secondary to expanded blood volume.     

Physical training alters the pathogenesis of pacing-induced heart failure through endothelium-mediated mechanisms in awake dogs

BACKGROUND: Beneficial effects of exercise training on cardiovascular function in chronic heart failure (CHF) have been suggested previously, but the underlying mechanisms are unknown. We tested whether daily exercise training improves systemic hemodynamics and preserves endothelium-mediated vasodilator function during development of heart failure. METHODS AND RESULTS: Fifteen dogs were surgically instrumented for hemodynamic measurements. One group of dogs underwent 4 weeks of cardiac pacing (210 bpm for 3 weeks and 240 bpm during week 4), and another group underwent pacing plus daily exercise training (4.4+/-0.3 km/h, 2 h/d). Pacing-alone dogs developed CHF characterized by typical hemodynamic abnormalities, blunted endothelium-mediated vasodilator function in coronary and femoral circulations, and decreased gene expression of endothelial constitutive nitric oxide synthase (ECNOS, normalized to GAPDH expression; normal, 1.15+/-0.31 versus CHF, 0.29+/-0.08, P<.05). Exercise training preserved normal hemodynamics at rest, endothelium-mediated vasodilator function, and gene expression of ECNOS (0.72+/-0.16 versus normal, P=NS). Inhibition of NO synthesis (nitro-L-arginine) in exercise-trained dogs abolished the preserved endothelium-mediated vasodilation of epicardial coronary arteries and elevated left ventricular end-diastolic pressure (7.7+/-0.3 to 19+/-3.4 mm Hg, P<.05), suggesting that the preservation of resting hemodynamics was in large part due to preserved endothelial function concealing the underlying CHF state. CONCLUSIONS: Long-term exercise training altered the natural history of heart failure due to rapid cardiac pacing. One of the underlying mechanisms is through the preservation of endothelial vasodilator function.     

Impairment of autonomically mediated heart rate control in patients with cardiac dysfunction

Patients with cardiac disorders have defective parasympathetic control of heart rate. To evaluate the possibility of similar changes in sympathetic control of heart rate, we compared reflex chronotropic responses to 80 degree upright tilt and nitroglycerin-induced hypotension in 31 cardiac patients and 7 normal individuals before and after partial parasympathetic blockade with atropine. Tilting revealed an attenuation of the normal heart rate increase in patients; the magnitude of this defect was greatest in patients with more severe symptoms (class III) and evidence of left ventricular dysfunction (the heart rate increase averaged 25 plus or minus 3 beats/min in normal subjects, 12 plus or minus 2 beats/min in class I-II patients, and 7 plus or minus 1 beats/min in class III patients). Class III symptoms due to mechanical causes (mitral stenosis), however, were not associated with this defect. A marked reduction in heart rate rise with hypotension was seen only in those class III patients without mitral stenosis (0.4 plus or minus 0.1 beats min-minus 1 mm Hg-minus 1 vs. 3.0 plus or minus 0.5 beats min-minus 1 mm Hg-minus 1 in normal subjects). This abnormality also persisted after atropine administration, thus confirming a defect in the sympathetic as well as the parasympathetic component of baroreceptor-mediated reflex heart rate control in patients with cardiac dysfunction. Infusions of isoproterenol produced equivalent rises in heart rate in patients and normal individuals, excluding a reduction in beta-receptor responsiveness as a cause of impaired sympathetic influence. Norepinephrine depletion, however, is a well-recognized concomitant of cardiac failure. It is possible that the reduction in sympathetically mediated heart rate responses results in part from depletion of the sympathetic neurotransmitter.     

Modification of exercise performance by sharp reduction of blood pressure. A study in patients with uncomplicated hypertension

We evaluated exercise performance in 14 patients with uncomplicated essential hypertension 1 h after the administration of a single dose of placebo, nifedipine (20 mg), captopril (50 mg), and propranolol (80 mg). Drugs were administered at the same time of day following a randomized, double-blind protocol. Mean resting blood pressure (+/- SE) was 135 +/- 3 mm Hg with placebo administration, 118 +/- 4 with captopril, 110 +/- 4 with nifedipine, and 115 +/- 5 with propranolol and increased with exercise to 163 +/- 4, 146 +/- 3, 136 +/- 4, 136 +/- 4, respectively. Oxygen consumption at peak exercise and at ventilatory anaerobic threshold (VAT) was 25.2 +/- 1.1 and 18.1 +/- 1.0 ml/min/kg with placebo. Only propranolol (-2.3 ml/min/kg) decreased peak exercise oxygen consumption. Oxygen consumption at VAT was reduced by nifedipine and propranolol but unaffected by captopril. The effects on exercise capacity of blood pressure reduction in hypertensive patients are dependent on the drug utilized and are not related to the amount of blood pressure reduction. The lowered oxygen consumption at VAT observed with nifedipine and propranolol, and not with captopril, might be due to an excessive downward shift of the muscle perfusion pressure--oxygen consumption relationship which might take place during exercise.     

Replication bypass and mutagenic effect of alpha-deoxyadenosine site-specifically incorporated into single-stranded vectors

OBJECTIVES: The aims of the study were to 1) assess the effects of 12 weeks of exercise training at low work loads (i.e., corresponding to < or = 50% of peak oxygen consumption [Vo2]) on peak Vo2 and hyperemic calf blood flow in patients with severe congestive heart failure; and 2) evaluate left ventricular diastolic pressure and wall stress during exercise performed at work loads corresponding to < or = 50% and 70% to 80% of peak Vo2. BACKGROUND: Whether the benefits of exercise training can be achieved at work loads that result in lower left ventricular diastolic wall stress than those associated with conventional work loads is unknown in patients with severe congestive heart failure. METHODS: Sixteen patients with severe congestive heart failure trained at low work loads for 1 h/day, four times a week, for 12 weeks. Peak Vo2 and calf and forearm reactive hyperemia were measured before and during training. Nine of the 16 patients underwent right heart catheterization and echocardiography during bicycle exercise at low and conventional work loads (i.e., 50% and 70% to 80% of peak Vo2, respectively). RESULTS: The increase in left ventricular diastolic wall stress was substantially lower during exercise at low work loads than during exercise at conventional work loads, (i.e., [mean +/- SEM] 23.3 +/- 7.4 vs. 69.6 +/- 8.1 dynes/cm2 (p < 0.001). After 6 and 12 weeks of training, peak Vo2 increased from 11.5 +/- 0.4 to 14.0 +/- 0.5 and 15.0 +/- 0.5 ml/kg per min, respectively (p < 0.0001 vs. baseline for both). Peak reactive hyperemia significantly increased in the calf but not in the forearm. The increases in peak Vo2 and calf peak reactive hyperemia correlated closely (r = 0.61, p < 0.02). CONCLUSIONS: In patients with severe congestive heart failure, peak Vo2 is enhanced by exercise training at work loads that result in smaller increases in left ventricular diastolic wall stress than those observed at conventional work loads.     

Hemodynamic and norepinephrine responses to pacing-induced heart failure in conscious sinoaortic-denervated dogs

The present study was undertaken to determine the effects of chronic sinoaortic (baroreceptor) denervation (SAD) on the hemodynamic and sympathetic alterations that occur in the pacing-induced model of congestive heart failure. Two groups of dogs were examined: intact (n = 9) and SAD (n = 9). Both groups of dogs were studied in the control (prepace) state and each week after the initiation of ventricular pacing at 250 beats/min. After the pacemaker was turned off, hemodynamic and plasma norepinephrine levels returned toward control levels in the prepaced state and after 1 and 2 wk of pacing. However, by 3 wk all hemodynamic and norepinephrine levels remained relatively constant over the 10-min observation period with the pacemaker off. With the pacemaker off, left ventricular end-diastolic pressure went from 2.7 +/- 1.4 (SE) mmHg during the prepace state to 23.2 +/- 2.9 mmHg in the heart failure state in intact dogs (P < 0.01). Left ventricular end-diastolic pressure increased to 27.1 +/- 2.2 mmHg from a control level of 4.2 +/- 1.9 mmHg i SAD dogs (P < 0.0003). Mean arterial pressure significantly decreased in intact and SAD dogs. Resting heart rate was significantly higher in SAD dogs and increased to 135.8 +/- 8.9 beats/min in intact dogs and 136.1 +/- 6.5 beats/min in SAD dogs. There were no significant differences in the hemodynamic parameters between intact and SAD dogs after pacing. Plasma norepinephrine was significantly lower in intact than in SAD dogs before pacing (197.7 +/- 21.6 vs. 320.6 +/- 26.6 pg/ml; P < 0.005). In the heart failure state, plasma norepinephrine increased significantly in both intact (598.3 +/- 44.2 pg/ml) and SAD (644.0 +/- 64.6 pg/ml) groups. There were no differences in the severity or the magnitude of the developed heart failure state in SAD vs. intact dogs. We conclude from these date that the arterial baroreflex is not the sole mechanism for the increase in sympathetic drive in heart failure.     

Antihypertensive effects of food-intake restriction in aortic coarctation hypertension

OBJECTIVE: To test the hypothesis that reductions in mean arterial pressure (MAP) induced by food-intake restriction in aortic coarctation hypertension are the result of a reduction of the sympathetic support of the MAP. We also wanted to determine whether the baroreflex control of the heart rate, and alpha- and beta-adrenergic responsivenesses were influenced by chronic food-intake restriction. METHODS: Four days after aortic coarctation, female Sprague-Dawley rats were assigned to a group that had access ad libitum to food (CON; n = 19) or to a food-intake-restricted group (FRG; n = 17) that was allowed 60% of the CON group's food intake per rat. After 3 weeks, carotid and jugular catheters were implanted for measurement of the MAP and infusion of drugs into conscious rats. The sympathetic contribution to the blood pressure was assessed by measuring the depressor response to ganglionic blockade by hexamethonium plus atropine (30.0 and 0.1 mg/kg intravenously). The baroreflex control of the heart rate was assessed by administering alternating bolus doses of phenylephrine and nitroprusside. The alpha-adrenergic sensitivity was assessed by measuring the response of the MAP to phenylephrine in areflexive rats (after ganglionic blockade), and the beta-adrenergic sensitivity was assessed by measuring the responses of the MAP and heart rate to isoproterenol administration both in reflexive and in areflexive rats. RESULTS: Four days after catheterization, both the MAP (CON 150 +/- 5 mmHg, FRG 116 +/- 4 mmHg) and the heart rate (CON 414 +/- 8 beats/min, FRG 365 +/- 11 beats/min) were significantly lower in rats of the FRG. That the sympathetic support of the MAP had diminished in FRG rats was evidenced by an attenuated depressor response to ganglionic blockade (40 +/- 3 versus 65 +/- 3 mmHg). FRG rats exhibited significantly greater reflex bradycardia in response to phenylephrine (slope -1.44+/- 0.07 versus -0.54 +/- 0.05 beats/min per mmHg), whereas their reflex tachycardia was not altered (slope -1.58 +/- 0.08 versus -1.53 +/- 0.13 beats/min per mmHg). FRG rats also displayed blunted responses of the heart rate and MAP to isoproterenol administration. CONCLUSION: Food-intake restriction attenuates the rise in MAP which occurs after aortic coarctation significantly. The antihypertensive effect of food-intake restriction may be mediated via a reduction in sympathetic tone.     

Cardiovascular and metabolic responses to adrenaline infusion in patients with short-term hypothyroidism

OBJECTIVE: The relation between the clinical manifestations of thyroid disease (both hypo and hyper-thyroidism) and tissue sensitivity to catecholamines remains uncertain. It has been suggested that tissue adrenergic responsiveness is decreased in hypothyroidism, but the reports have been conflicting and have invariably focused on a single physiological response. Therefore the aim of the present study was to determine in patients with moderate, short-term, symptomatic hypothyroidism the responses of heart rate, systolic and diastolic blood pressure, forearm blood flow and metabolic rate to adrenaline infused at a rate known to achieve plasma concentrations in the middle of the physiological range. PATIENTS: Ten subjects (5M, age 43 +/- 3 years, mean +/- SEM) were studied. All were on thyroxine replacement for hypothyroidism following either thyroidectomy or radioactive iodine and had been biochemically euthyroid for at least 6 months. DESIGN: Studies were performed in random order. One study was undertaken on full replacement therapy and the other after 50 micrograms thyroxine daily for 2 weeks. After basal, supine measurements adrenaline was infused at 25 ng/kg/min for 30 minutes. MEASUREMENTS: Heart rate, blood pressure, blood glucose, metabolic rate and forearm blood flow were measured at rest and at 10-minute intervals throughout the adrenaline infusion. RESULTS: Free T4 (10.6 +/- 1.3 vs 17.6 +/- 2.0 pmol/l, P < 0.001) and free T3 (3.6 +/- 0.2 vs 4.6 +/- 0.3 pmol/l, P < 0.01) concentrations were significantly lower on 50 micrograms thyroxine than full replacement therapy. Fasting blood glucose concentrations (4.7 +/- 0.2 vs 4.7 +/- 0.1 mmol/l) were similar. The resting adrenaline concentrations were comparable, 0.29 +/- 0.18 and 0.24 +/- 0.14 nmol/l on 50 micrograms thyroxine and full replacement therapy respectively, and increased to a similar level (2.36 +/- 0.39 and 2.36 +/- 0.35 nmol/l) throughout the adrenaline infusion. The resting heart rate and metabolic rate were significantly lower on 50 micrograms thyroxine than full replacement therapy (68 +/- 2 vs 72 +/- 3 beats/min, P < 0.01; and 4.48 +/- 0.35 vs 4.88 +/- 0.39 kJ/min, P < 0.01) respectively, but the increase in heart rate (7 +/- 2 vs 8 +/- 2 beats/min) and metabolic rate (0.43 +/- 0.09 vs 0.43 +/- 0.06 kJ/min) did not differ on the two study days. Resting systolic blood pressure, diastolic blood pressure and forearm blood flow were comparable on 50 micrograms thyroxine and full replacement therapy as were the changes in systolic blood pressure (1 +/- 1 vs 1 +/- 1 mmHg), diastolic blood pressure (-7 +/- 2 vs -7 +/- 1 mmHg), forearm blood flow (1.4 +/- 0.1 vs 1.7 +/- 0.2 ml/min/100ml forearm) and blood glucose concentration (0.7 +/- 0.1 vs 0.7 +/- 0.1 mmol/l). CONCLUSIONS: Patients with short-term hypothyroidism appear to have a normal response to adrenaline infusion despite reduced baseline heart rate and metabolic rate. Thus, under physiological and mild pathophysiological conditions there appears to be no evidence of any synergy between thyroid status and sensitivity to catecholamines.     

Mercury exposure of maroon workers in the small scale gold mining in Suriname

Recent studies have reported reduced immunity in trained athletes. Scant information exists on changes in the immune function among trained children. The purpose of this study was to assess the effect of aerobic exercise on the phagocytic process of neutrophils and the complement system in young athletes. Subjects included prepubertal elite female gymnasts (n = 7) and untrained girls (n = 6) aged 10-12 years. Venous blood was withdrawn before, immediately post and 24 h following a 20-min run at a heart rate of 170-180 beats.min-1. Neutrophil random migration, chemotactic activity, bactericidal function and PMA/FMLP-stimulated superoxide anion release as well as various complement components were assessed. Net chemotaxis was found reduced (P < 0.05) 24 h following exercise (58 +/- 11 vs. 36 +/- 11 cells/field in gymnasts and 47 +/- 7 vs. 42 +/- 8 cells/field in untrained girls pre- and 24 h post-exercise, respectively). The basal values, as well as post-exercise values of bactericidal activity were lower (P < 0.05) in gymnasts as compared with the control group (0.8 +/- 0.3, 0.8 +/- 0.2 and 0.8 +/- 0.1 log decrease of colonies in gymnasts at pre-, immediately post-, and 24 h post-exercise, respectively and 1.1 +/- 0.1, 1.1 +/- 0.1 and 1.0 +/- 0.2 log decrease of colonies in controls, respectively). No significant effect on the bactericidal activity was observed in either group following exercise. The addition of homologous sera did not correct the bactericidal activity. PMA-stimulated superoxide anion release decreased (P < 0.05) among gymnasts immediately following exercise (5.7 +/- 0.4 vs. 4.4 +/- 1.0 mmol O2/10(6) PMN.min) and remained low 24 h later. The same trend was observed in FMLP-stimulated neutrophils but the data were not significant. Significantly decreased levels (P < 0.05) of the early complement components (C1Q, C1R) were also found following exercise (1.34 +/- 0.64 vs. 1.27 +/- 0.28 and 1.09 +/- 0.07 vs. 1.02 +/- 0.06 pre- and post-exercise in gymnasts and untrained, respectively). Furthermore, consistently lower C2 and C3 were observed in gymnasts compared with controls. Neutrophil dysfunction as well as impairment of the complement system seem to occur following exercise.     

Recovery of respiratory sinus arrhythmia in detoxified alcoholic subjects

Although most alcoholic subjects show little autonomic dysfunction, severe alcoholic subjects may have pathological changes in autonomic nerves. We asked if respiratory sinus arrhythmia amplitude (RSA), an index of vagal cardiac control, is decreased in alcoholism and, if so, whether the decrease is reversed with abstinence. RSA was assessed in 17 normotensive alcoholic subjects (A) at 1, 4, 12, and 24 wk of abstinence after detoxification and at similar intervals in 17 controls (C) matched for age, race, and gender. Subjects were studied in both supine and seated positions while breathing in a prescribed deep (> 50% vital capacity) and slow (5-7/min) pattern. Mean heart rate (HR) was determined over 30 s from the electrocardiogram; RSA (the difference between maximum and minimum instantaneous HRs after inspiratory onset) was determined from 10 consecutive breaths. In C, both HR (supine: 61.5 +/- 2.2 beats/min; seated: 71.3 +/- 1.7 beats/min; P < 0.002) and RSA (supine: 22.5 +/- 1.0 beats/min; seated: 28.4 +/- 1.4 beats/min; P < 0.003) were higher when seated than when supine, but neither HR nor RSA varied over 24 wk. At week 1 of abstinence, HRs for A were higher than those for C (supine: 74.2 +/- 2.3 beats/min, P < 0.001; seated: 83.2 +/- 2.7 beats/min, P < 0.003), but by week 24, both seated and supine values returned to control levels. RSA in A at week 1, was only one-half that of C (supine: 11.1 +/- 1.4 beats/min, P < 0.001; seated: 14.7 +/- 1.9 beats/min, P < 0.001) and independent of body position.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic effects of sub-chronic NO synthase inhibition in conscious dogs: role of EDRF/NO in muscular exertion

Acute and chronic administration of nitric oxide (NO) synthase (NOS) inhibitors increase mean arterial blood pressure (MAP) in rats but their hemodynamic effects in other species remain unknown. Moreover, the role of NO in the control of exercise-induced vasodilation is still debated. To answer these questions, six dogs were instrumented for the continuous measurement of cardiac output (CO, electromagnetic flow probe on the aorta), MAP (aortic catheter) and left ventricular pressure (Konigsberg gauge). Total peripheral resistance (TPR) was calculated as MAP/CO ratio and dP/dt was used as an index of cardiac inotropism. The dogs were treated from day 0 (D0) to 7 (D7) by the NOS inhibitor, N omega-nitro-L-arginine (L-NNA), 20 mg/kg/day (IV). Such a dose regimen resulted in NOS inhibition evidenced (a) in vivo by a reduction of the hypotensive responses to graded doses of acetylcholine and bradykinin, (b) ex vivo by a decrease in the relaxation of the femoral artery to acetylcholine (EC 50 = 2.2 +/- 0.6 10(-7) M after L-NNA vs 2.2 +/- 0.8 10(-8) M in controls). One month after instrumentation, the dogs being conscious, MAP measured at rest remained unchanged following one week L-NNA treatment (from 90 +/- 2 at D0 to 91 +/- 5 mmHg at D7). However, TPR increased (from 3,600 +/- 290 at D0 to 6,300 +/- 510 dyn.s.cm-5 at D7) and CO decreased (from 2.1 +/- 0.2 at D0 to 1.2 +/- 0.1 l/min at D7) (all p < 0.01), partly as the result of a marked bradycardia (from 100 +/- 7 at D0 to 60 +/- 7 beats/min at D7). L-NNA induced-increase in TPR was completely reversed by a bolus injection of nitroglycerin (10 micrograms/kg). During treadmill exercise (12 km/h), heart rate (251 +/- 9 at D0 vs 226 +/- 11 beats/min at D7), CO (6.3 +/- 0.9 at D0 vs 4.3 +/- 0.7 l/min at D7) and stroke volume remained significantly lower, and TPR significantly higher (1,662 +/- 278 at D0 vs 2,621 +/- 489 dyn.s.cm-5 at D7) after L-NNA than in the control state. Thus, NOS inhibition in resting conscious dogs by L-NNA markedly increases peripheral resistance but does not increase arterial pressure. In addition, L-NNA blunts both exercise-induced peripheral vasodilation and increase in cardiac output, despite metabolic vasodilation.     

Aerobic exercise capacity remains normal despite impaired endothelial function in the micro- and macrocirculation of physically active IDDM patients

The aim of the present study was to examine if diabetes in the absence of neuropathy affects the exercising capacity of IDDM patients, and whether regular, intense training has a beneficial effect on endothelial function. Five groups of subjects were studied: 23 healthy control subjects who exercised regularly (age 33 +/- 6 years), 23 nonneuropathic type 1 diabetic patients who exercised regularly (age 33 +/- 6 years, IDDM duration 11 +/- 8 years), 7 neuropathic type 1 diabetic patients who exercised regularly (age 36 +/- 7 years, IDDM duration 22 +/- 8 years), 18 healthy subjects who did not exercise regularly (age 34 +/- 7 years), and 5 nonneuropathic type 1 diabetic patients who did not exercise regularly (age 31 +/- 4 years, IDDM duration 20 +/- 3 years). All groups were matched for age, sex, and body weight. No differences existed in the energy expenditure per week in physical activity among the three exercising groups or between the two nonexercising groups. The maximal oxygen uptake was similar between control and diabetic nonneuropathic exercisers, and among diabetic neuropathic exercisers, control nonexercisers, and diabetic nonexercisers; however, a significant difference existed between the first two and the last three groups (P < 0.0001). A stepwise increase was found in the resting heart rate among the groups, ranging from the lowest in control exercisers to the highest in diabetic nonexercisers, but the maximal heart rate was lower only in diabetic neuropathic exercisers compared with all other groups (P < 0.05). Assessments of endothelial function in both macro- and microcirculation were performed in 12 control exercisers, 10 diabetic nonneuropathic exercisers, 5 diabetic neuropathic exercisers, 17 control nonexercisers, and 4 diabetic nonexercisers. When all diabetic patients were considered as one group and all control subjects as another, the microcirculation endothelial function in the diabetic group was reduced compared with the control subjects (91 +/- 49 vs. 122 +/- 41% flux increase over baseline; P < 0.05). In contrast, no differences existed among the three diabetic groups or between the two control groups. Similarly, in macrocirculation, a reduced response during reactive hyperemia was observed in the diabetic patients compared with control subjects (7.0 +/- 4.5 vs. 11.2 +/- 6.6% diameter increase; P < 0.05), whereas again no difference existed among the three diabetic groups or between the two control groups. These data suggest that diabetes per se does not affect aerobic exercise capacity (VO2max) in physically active individuals, but is reduced in the presence of neuropathy. In addition, regular exercise training involving the lower extremities does not improve the endothelial function in the micro- and macrocirculation of the nonexercised upper extremity in type 1 diabetic patients.     

Mechanisms for increasing stroke volume during static exercise with fixed heart rate in humans

Ten patients with preserved inotropic function having a dual-chamber (right atrium and right ventricle) pacemaker placed for complete heart block were studied. They performed static one-legged knee extension at 20% of their maximal voluntary contraction for 5 min during three conditions: 1) atrioventricular sensing and pacing mode [normal increase in heart rate (HR; DDD)], 2) HR fixed at the resting value (DOO-Rest; 73 +/- 3 beats/min), and 3) HR fixed at peak exercise rate (DOO-Ex; 107 +/- 4 beats/min). During control exercise (DDD mode), mean arterial pressure (MAP) increased by 25 mmHg with no change in stroke volume (SV) or systemic vascular resistance. During DOO-Rest and DOO-Ex, MAP increased (+25 and +29 mmHg, respectively) because of a SV-dependent increase in cardiac output (+1.3 and +1.8 l/min, respectively). The increase in SV during DOO-Rest utilized a combination of increased contractility and the Frank-Starling mechanism (end-diastolic volume 118-136 ml). However, during DOO-Ex, a greater left ventricular contractility (end-systolic volume 55-38 ml) mediated the increase in SV.