Growth hormone secretion during sleep

Plasma growth hormone (GH), insulin, cortisol, and glucose were measured during sleep on 38 nights in eight young adults. Blood was drawn from an indwelling catheter at 30-min intervals; EEG and electrooculogram were recorded throughout the night. In seven subjects, a plasma GH peak (13-72 mmug/ml) lasting 1.5-3.5 hr appeared with the onset of deep sleep. Smaller GH peaks (6-14 mmug/ml) occasionally appeared during subsequent deep sleep phases. Peak GH secretion was delayed if the onset of sleep was delayed. Subjects who were awakened for 2-3 hr and allowed to return to sleep exhibited another peak of GH secretion (14-46 mmug/ml). Peak GH secretion was not correlated with changes in plasma glucose, insulin, and cortisol. The effects of 6-CNS-active drugs on sleep-related GH secretion were investigated. Imipramine (50 mg) completely abolished GH peaks in two of four subjects, whereas chlorpromazine (30 mg), phenobarbital (97 mg), diphenylhydantoin (90 mg), chlordiazepoxide (20 mg), and isocarboxazid (30 mg) did not inhibit GH peaks. Altered hypothalamic activity associated with initiation of sleep results in a major peak of growth hormone secretion unrelated to hypoglycemia or changes in cortisol and insulin secretion.     

Adrenergic regulation of lipolysis in situ at rest and during exercise.

The adrenergic regulation of lipolysis was investigated in situ at rest and during standardized bicycle exercise in nonobese healthy subjects, using microdialysis of the extracellular space in subcutaneous adipose tissue. The glycerol concentration was about two times greater in adipose tissue than in venous blood. At rest, the glycerol concentration in adipose tissue was rapidly increased by 100% (P less than 0.01) after the addition of phentolamine to the ingoing perfusate, whereas addition of propranolol did not alter the adipose tissue glycerol level. Glycerol in adipose tissue and plasma increased during exercise and decreased in the postexercise period. Propranolol in the perfusate almost completely inhibited the increase in the tissue dialysate glycerol during the exercise-postexercise period. Phentolamine, however, was completely ineffective in this respect. During exercise, the lipolytic activity was significantly more marked in abdominal than in gluteal adipose tissue; this was much more apparent in women than in men. Thus, in vivo lipolysis in subcutaneous adipose tissue is regulated by different adrenergic mechanisms at rest and during exercise. Alpha-adrenergic inhibitory effects modulate lipolysis at rest, whereas beta-adrenergic stimulatory effects modulate lipolysis during exercise. In addition, regional differences in lipolysis are present in vivo during exercise, which seem governed by factors relating to sex.     

Mucociliary clearance in healthy men at rest and during exercise

Summary. We measured mucociliary clearance at rest and during exercise in 11 healthy non-smoking men. The subjects inhaled an aerosol containing [⁹⁹Tc^m]albumin millimicrospheres with deep inhalations. Four sets of scintigraphic images were obtained with 15-min intervals. Lung retention of radioactivity was quantified using a gamma camera and the clearance of particles from the lungs calculated for each 15-min period. The first image was obtained directly after inhalation, the second after a period of 15-min rest, the third after a period of exercise on a bicycle ergometer (workload approximately 80% of predicted maximum capacity) and the final fourth image after another period of rest. We found small differences in clearance rate at rest and during exercise indicating that there is no substantial change in the clearance rate during exercise in normal subjects.     

Diagnostic epidural opioid blockade in primary fibromyalgia at rest and during exercise

Nine patients with primary fibromyalgia participated. The patients were studied prior to, during and immediately after 4 identical periods of exercise (bicycle ergometer) each performed 30 min after injection with saline, repeated saline, an opioid and naloxone. All substances were given epidurally, except for naloxone which was given intravenously. Finally, with the patients resting in bed, lignocaine was injected epidurally. Physiological variables, general exertion, dyspnoea, lower extremity exhaustion, pain and tender points in the lower half of the body were examined. Resting pain and tender points diminished significantly after the opioid injection. Lignocaine completely abolished resting pain and tender points. Lower extremity exhaustion was reduced by the opioid. General exertion and dyspnoea were unaffected by the opioid. In conclusion the results support the hypothesis that the pain in fibromyalgia is of peripheral nociceptive or spinal origin. We raise the hypothesis that the fatigability is, at least partly, due to inhibition because of pain.     

Ventilatory responses to inhaled carbon dioxide at rest and during exercise in man

1. Rapid steady-state CO2 responses were determined in six normal subjects at rest and five subjects at four different work loads up to 125 W, by injecting pure CO2 at constant flow into a small mixing chamber in the inspiratory limb of a breathing circuit. 2. The time course of the response of ventilation (V) and mean alveolar PCO2 (PACO2) was checked in separate experiments, where the flow rate of injected CO2 was changed abruptly and the effects were followed for 10 min. 3. V and PACO2 were measured every breath, and the results ensemble-averaged for each subject (two or three runs per subject) and then for the groups as a whole, in 30 s or 60 s time bins. 4. PACO2 during exercise was estimated by graphical reconstruction from the sloping alveolar plateau, and separately by the empirical equation of Jones, Robertson & Kane [1]. At rest, PACO2 was assumed equal to end-tidal PCO2 (PetCO2). 5. With the constant inflow technique, 4 min was required to reach steady-state V and PACO2 during exercise, and 6 min at rest. 6. At rest, with 4 min steps (doubtful steady state) the averaged CO2 response was concave up. With 6 min steps the response was almost linear. In neither case was the deviation from linearity statistically significant. 7. During exercise, the averaged CO2 responses were essentially isocapnic at work loads greater than 75 W with either method of deriving PACO2.     

Substrate utilization in non-obese Type II diabetic patients at rest and during exercise

Recently, we observed that impairments exist in skeletal muscle free fatty acid (FFA) utilization during exercise in obese subjects with Type II diabetes. The main objective of the present study was to investigate whether plasma FFA oxidation is impaired during exercise in non-obese Type II diabetic patients. Stable isotope tracers of palmitate and glucose were infused for 2 h at rest and 1h of bicycle exercise at 40% peak oxygen consumption ( V*O(2)max) in volunteers with Type II diabetes and a healthy control group. At rest, plasma FFA oxidation was not significantly different between subjects with Type II diabetes and control subjects (2.13+/-0.51 versus 1.93+/-0.54 micromol.kg(-1).min(-1) respectively). During exercise, Type II diabetic patients and control subjects had similar rates of total fat [Type II diabetes, 9.62+/-1.84 micromol.kg(-1).min(-1); control, 12.08+/-4.59 micromol.kg(-1).min(-1); not significant (NS)] and glucose oxidation (Type II diabetes, 44.24+/-10.36 micromol.kg(-1).min(-1); control, 57.37+/-14.54 micromol.kg(-1).min(-1); NS). No aberrations were present in plasma FFA uptake [rate of disappearance ( Rd ); Type II diabetes, 11.78+/-4.82; control, 10.84+/-3.39; NS] and oxidation rates (Type II diabetes 8.10+/-1.44; control 8.00+/-3.12, NS) in Type II diabetic patients; triacylglycerol-derived fatty acid oxidation was 2.6-fold lower in Type II diabetic patients than in control subjects, but this difference was not statistically significant. Muscle glycogen oxidation was lower in diabetes patients than in control subjects (Type II diabetes, 25.16+/-13.82 micromol.kg(-1).min(-1); control, 42.04+/-10.58 micromol.kg(-1).min(-1); P <0.05) and plasma glucose contributed more to energy expenditure in Type II diabetes (26+/-3% in diabetic versus 15+/-2% in control, P <0.05). We conclude that plasma FFA oxidation is not impaired during exercise in non-obese Type II diabetic patients. The data confirm that Type II diabetes is a heterogeneous disease, and that the adaptation at the substrate level differs between obese and non-obese patients and may contribute to differences in the final appearance of the various phenotypes.     

Heart rate variability at rest and during exercise in persons with Down syndrome

OBJECTIVES: To determine whether autonomic dysfunction explains chronotropic incompetence observed in persons with Down syndrome (DS) and to measure heart rate variability (HRV) at rest and during exercise in persons with mental retardation with and without DS. DESIGN: Comparative study. SETTING: University exercise science laboratory. PARTICIPANTS: Thirty-one subjects with mental retardation (age, 20.2 y) with DS (n=16; 10 men, 6 women) and without DS (n=15; 8 men, 7 women). INTERVENTIONS: Not applicable.Main outcome measures HRV was determined at rest and at 2 steady-state exercise intensities on the treadmill in both time (standard deviation of the R-R interval, percentage of R-R intervals deviating by more than 50 ms from the previous R-R interval [deviation >50], square root of the mean squared differences of successive differences) and frequency (low-frequency power [LF]), high-frequency power [HF], the LF/HF ratio) domains. RESULTS: The DS group demonstrated a statistically lower peak heart rate (161 beats/min vs 178 beats/min, P<.05), and peak oxygen consumption (27.4 mL.kg(-1).min(-1) vs 34.3 mL. kg(-1).min(-1), P<.05) than did the group with mental retardation without DS. At rest, all time domain measures of HRV and absolute HF power were significantly higher in the DS group (P<.05). Yet, LF power and LF/HF values did not differ between groups. All HRV variables decreased significantly at both exercise intensities, with no differences between groups during exercise (P<.05). CONCLUSIONS: People with DS have greater parasympathetic activity at rest, but group differences disappear with the onset of exercise, which suggests that other variables are responsible for chronotropic incompetence in persons with DS.     

Quantitative radiocardiographic evaluation of cardiac dynamics in man at rest and during exercise

113Inm radiocardiography in conjunction with a gamma camera and a digital computer is applied to measurements of cardiac output, stroke volume, ejection fraction, end-diastolic volume, pulmonary blood volume, pulmonary transfer time and dispersion both at rest and during muscular exercise. A modified gamma function is used in calculations of radiocardiographic curves. In twelve supine male subjects the maximal increase of cardiac output was 220%, stroke volume 30%, ejection fraction 15%, and pulmonary blood volume 30%. The present method provides a non-invasive tool for cardiovascular examinations during exercise.     

Acute and short-term effects of nitrendipine and diltiazem at rest and during exercise in hypertensive patients.

The subjects were 30 patients with mild-to-moderate hypertension randomly assigned to receive 10 mg of nitrendipine twice daily or 60 mg of diltiazem thrice daily for 14 days. On days 1 and 14 the patients performed an effort test (to a maximum of 100 W) before and after drug administration. Both nitrendipine and diltiazem reduced systolic and diastolic blood pressure; after 14 days of treatment, the reductions in blood pressure were significantly greater in the nitrendipine-treated patients than in the diltiazem-treated patients. Blood pressures were reduced at maximum effort in both treatment groups before drug administration on day 14 compared with day 1. Two hours after drug administration on days 1 and 14, the reductions in effort blood pressures were significantly greater after nitrendipine than after diltiazem. No side effects were noted in either group. It is concluded that nitrendipine is safe and effective in patients with mild-to-moderate hypertension at rest and during exercise.     

Influence of age on pulmonary haemodynamics at rest and during supine exercise

To determine the effects of age on the pulmonary circulation at rest and on exercise we analysed the results of right heart catheterization studies performed in 125 asymptomatic subjects aged 14-68 years, who were healthy or had indispositions which did not impair cardiac or pulmonary function. Age accounted for less than 10% of total variation in resting values of right atrial, pulmonary artery and wedge pressures, and of cardiac output. The pulmonary artery-wedge pressure gradient and flow resistance at rest significantly increased with age. On exercise there were significant increases with age in right atrial, pulmonary artery and wedge pressures, pulmonary to wedge pressure gradient and flow resistance, but cardiac output was not influenced by age. Pulmonary circulation variables at rest are mainly influenced by sex and size, but during exercise significant effects of age are apparent.     

Growth hormone secretion and sulfation factor activity in pseudohypoparathyroidism.

The role of growth hormone and serum sulfation factor in the pathogenesis of the short stature of pseudohypoparathyroidism was investigated in two adults with this syndrome. Growth hormone levels rose to 10.6 and 26.0 ng. per milliliter with insulin hypoglycemia, and reached 6.6 and 6.4 ng. per milliliter 120 minutes after 500 mg. of L-Dopa orally in these patients. Serum from both patients supported the incorporation of 35S-sulfate into chick embryo pelvic rudiments when incubated for 6 hours in a physiologic salt solution containing 13 amino acids. Pseudohypoparathyroid serum also stimulated the incorporation of radioactive sulfate into rat costal and xyphoid cartilage at a level similar to that observed with normal serum. It is concluded that growth hormone and sulfation factor deficiency are not implicated in the short statue of pseudohypoparathyroidism.     

Nasal, pulmonary and autoinhaled nitric oxide at rest and during moderate exercise

Objective: To investigate nasal nitric oxide (NO) excretion, pulmonary NO excretion, and autoinhalation of nasally released NO at rest compared with that during moderate exercise in smokers and non-smokers.¶Design: Prospective observational study.¶Setting: University laboratory.¶Participants: Fourteen healthy adult volunteers.¶Interventions: Breathing of NO-purified air supplied via a tube system at rest and during a bicycle-ergometer workload of 60 Watt over a time of 10 min.¶Measurement and results: We examined nasal and pulmonary NO excretion in smoking (n = 7) and non-smoking (n = 7) adult human volunteers. At rest, we measured constant nasal NO excretion rates of 311 ± 89 nl/min for non-smokers and 261 ± 142 nl/min for smokers (mean ± SD, n. s.). During 60 W exercise, nasal NO release remained unchanged, while pulmonary NO excretion doubled compared with the rates at rest (non-smokers: 40 ± 21 nl/min versus 23 ± 14 nl/min, p < 0.05; smokers: 41 ± 8 nl/min versus 22 ± 8 nl/min, p < 0.05). The differences between smokers and non-smokers in nasal or pulmonary NO excretion were not significant. To determine the autoinhaled amount of nasally released NO, we also measured the NO concentration within the nasopharynx of five volunteers during nasal breathing. The average inhaled NO concentration was 17.8 ± 3.1 ppb at rest and this decreased to 9.3 ± 1.8 ppb during exercise of 60 W, while minute ventilation approximately doubled from 9 ± 2 to 21 ± 3 l/min.¶Conclusion: Our results demonstrate that moderate exercise increased exclusively pulmonary NO excretion. Nasal NO release, which is 10 times higher at rest, was not changed. The decrease in autoinhaled NO concentration during exercise results from dilution of the continuous nasal release by the increased respiratory gas flow. The individual NO release allows no conclusion about smoking habits.     

Dietary-induced alterations in thyroid hormone metabolism during overnutrition.

Diet-induced alterations in thyroid hormone concentrations have been found in studies of long-term (7 mo) overfeeding in man (the Vermont Study). In these studies of weight gain in normal weight volunteers, increased calories were required to maintain weight after gain over and above that predicted from their increased size. This was associated with increased concentrations of triiodothyronine (T3). No change in the caloric requirement to maintain weight or concentrations of T3 was found after long-term (3 mo) fat overfeeding. In studies of short-term overfeeding (3 wk) the serum concentrations of T3 and its metabolic clearance were increased, resulting in a marked increase in the production rate of T3 irrespective of the composition of the diet overfed (carbohydrate 29.6 +/- 2.1 to 54.0 +/- 3.3, fat 28.2 +/- 3.7 to 49.1 +/- 3.4, and protein 31.2 +/- 2.1 to 53.2 +/- 3.7 microgram/d per 70 kg). Thyroxine production was unaltered by overfeeding (93.7 +/- 6.5 vs. 89.2 +/- 4.9 microgram/d per 70 kg). It is still speculative whether these dietary-induced alterations in thyroid hormone metabolism are responsible for the simultaneously increased expenditure of energy in these subjects and therefore might represent an important physiological adaptation in times of caloric affluence. During the weight-maintenance phases of the long-term overfeeding studies, concentrations of T3 were increased when carbohydrate was isocalorically substituted for fat in the diet. In short-term studies the peripheral concentrations of T3 and reverse T3 found during fasting were mimicked in direction, if not in degree, with equal or hypocaloric diets restricted in carbohydrate were fed. It is apparent from these studies that the caloric content as well as the composition of the diet, specifically, the carbohydrate content, can be important factors in regulating the peripheral metabolism of thyroid hormones.     

Adrenaline secretion during exercise

By studying six normal subjects during graduated treadmill exercise, we have confirmed that there is very little rise in venous plasma adrenaline levels during mild or moderate exercise. During a second study, adrenaline was infused intravenously in six resting subjects at a rate of 0.025 micrograms min-1 kg-1. This elevated the basal plasma adrenaline level from 0.28 +/- 0.04 nmol/l to 0.92 +/- 0.16, 1.16 +/- 0.20 and 1.28 +/- 0.19 nmol/l at 3, 5 and 7 min after the start of the infusion. The same adrenaline infusion was repeated in the same subjects 7 min after they started moderate exercise at a constant rate on a static exercise bicycle. Just before the start of the infusion, 7 min after the onset of exercise, plasma adrenaline had risen to 0.36 +/- 0.07 nmol/l. This rose to 1.86 +/- 0.30, 1.98 +/- 0.26 and 2.19 +/- 0.29 nmol/l at 3, 5 and 7 min after the start of this second infusion. Five minutes after the end of the infusion, while the subjects were still exercising, the mean level was 0.56 +/- 0.04 nmol/l. The venous plasma level of adrenaline is the result of a balance between the secretion of adrenaline by the adrenal medulla and the clearance of adrenaline from plasma. Our results suggest that the lack of any significant rise in plasma adrenaline during moderate exercise does not result from an accelerated clearance of adrenaline by exercising tissue. The clearance rate of adrenaline from plasma is reduced during exercise. There is no significant increase in secretion by the adrenal medulla in response to the stimulus of mild or moderate exercise.