Met-enkephalin, β-endorphin and cortisol responses to sub-maximal exercise after sleep disturbances

The present study compared the effects of partial sleep deprivation and the effects of an intake of a hypnotic compound (zolpidem) prior to bedtime, on sleep and on hormonal and metabolic adaptations to subsequent exercise. Sleep deprivation consisted of a delayed bedtime and an early getting-up time. Eight young subjects, who slept well and were highly trained athletes, were enrolled in this study. Sleep was recorded polygraphically and the following afternoon exercise was performed on a cycle ergometer for 30 min at 75% of maximal oxygen consumption (VO2max) after a 10-min warm up. Met-enkephalin, beta-endorphin, cortisol, and lactate concentrations were measured at rest and during exercise. The data obtained after experimental sleep, with and without medication were compared with those obtained in the reference condition with normal sleep. Both types of sleep reduction decreased the total sleep time, stage 2 sleep, and rapid eye movement sleep, whereas zolpidem administration did not modify either the duration of sleep or the sleep stages. After the reference night, plasma met-enkephalin did not show any significant change at the end of the submaximal exercise, whereas beta-endorphin, cortisol, and lactic acid concentrations increased significantly in all subjects. The changes in concentration in beta-endorphin were significantly related to the changes in cortisol (r = 0.78; P less than 0.01) and to the changes in plasma lactic acid (r = 0.58; P less than 0.05). Cortisol concentrations were also related to lactic acid values (r = 0.94; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of exhaustive submaximal exercise on cardiovascular function during sleep

The influence of an afternoon bout of exhaustive submaximal exercise on cardiovascular function and catecholamine excretion during sleep was examined in five female and four male subjects. Subjects walked on a treadmill for successive 50-min periods at 50, 60, and 70% maximal O2 consumption, separated by 10-min rest periods. Exercise terminated with volitional exhaustion. Following an adaptation night, electroencephalographic and impedance cardiographic measures were obtained during three successive nights of sleep, with exercise preceding night 3. Relative to the base-line night (night 2), exhaustive exercise resulted in a sustained elevation of heart rate and cardiac output throughout the entire night's sleep. The magnitude of these elevations was unaffected by sleep stage but decreased over the night. The typical pattern of circadian decline in cardiac output was unaltered. However, the decline in heart rate with sleep onset was greater on the exercise night. Changes in impedance dZ/dt and R-Z interval suggested an enhanced myocardial contractility during the first 3 h of sleep postexercise. Analysis of morning urine samples revealed that in seven of nine subjects norepinephrine excretion increased, epinephrine excretion decreased, and dopamine excretion was unchanged during sleep on the exercise night. It is suggested that these cardiac changes reflect a sustained increase in myocardial beta-receptor activity.     

Sleep processes exert a predominant influence on the 24-h profile of heart rate variability

Adverse cardiovascular events are known to exhibit 24-h variations with a peak incidence in the morning hours and a nonuniform distribution during the night. The authors examined whether these 24-h variations could be related to circadian or sleep-related changes in heart rate (HR) and in HR variability (HRV). To differentiate the effect of circadian and sleep-related influences, independent of posture and of meal ingestion, seven normal subjects were studied over 24 h, once with nocturnal sleep from 2300 to 0700 h and once after a night of sleep deprivation followed by 8 h of daytime sleep from 0700 to 1500 h. The subjects were submitted to constant conditions (continuous enteral nutrition and bed rest). HRV was calculated every 5 min using two indexes: the standard deviation of normal R-R intervals (SDNN) and the ratio of low-frequency to low-frequency plus high-frequency power. Sleep processes exerted a predominant influence on the 24-h profiles of HR and HRV, with lowest HRV levels during slow wave sleep, high levels during REM sleep and intrasleep awakenings, and abrupt increases in HR at each transition from deeper sleep to lighter sleep or awakenings. The circadian influence was smaller, except for SDNN, which displayed a nocturnal increase of 140% whether the subjects slept or not. This study demonstrates that 24-h variations in HR and HRV are little influenced by the circadian clock andare mainly sleep-stage dependent. The results suggest an important role for exogenous factors in the morning increase in cardiovascular events. During sleep, the sudden rises in HR at each transition from deeper sleep to lighter sleep or awakenings might precipitate the adverse cardiac events.     

Bradyarrythmias in the obstructive sleep apnea sundrome: a dangerous complication or defense mechanism?

Sleep is characterized by cycling and consecutive alternation of different phases and stages, each of which features intrinsic changes in autonomic regulation with heart rate oscillations; this may cause heart rhythm disorders, especially in the presence of comorbidities. This review addresses the issues of interrelationship between cardiac conduction disorders and obstructive sleep apnea. It is shown that some mechanisms of bradyarrythmia emergence (first of all, features of autonomic regulation with increases in parasympathetic tone) under respiratory arrest during sleep are also inherent to human divers as well as aquatic or para-aquatic mammals that have to hold their breath when diving or staying under water for a long time. These mechanisms may fulfill the defense function.     

Different times of day do not change heart rate variability recovery after light exercise in sedentary subjects: 24 hours Holter monitoring

Incidence of cardiovascular events follows a circadian rhythm with peak occurrence during morning. Disturbance of autonomic control caused by exercise had raised the question of the safety in morning exercise and its recovery. Furthermore, we sought to investigate whether light aerobic exercise performed at night would increase HR and decrease HRV during sleep. Therefore, the aim of this study was to test the hypothesis that morning exercise would delay HR and HRV recovery after light aerobic exercise, additionally, we tested the impact of late night light aerobic exercise on HR and HRV during sleep in sedentary subjects. Nine sedentary healthy men (age 24 ± 3 yr; height 180 ± 5 cm; weight 79 ± 8 kg; fat 12 ± 3%; mean±SD) performed 35 min of cycling exercise, at an intensity of first anaerobic threshold, at three times of day (7 a.m., 2 p.m. and 11 p.m.). R-R intervals were recorded during exercise and during short-time (60 min) and long-time recovery (24 hours) after cycling exercise. Exercise evoked increase in HR and decrease in HRV, and different times of day did not change the magnitude (p < 0.05 for time). Morning exercise did not delay exercise recovery, HR was similar to rest after 15 minutes recovery and HRV was similar to rest after 30 minutes recovery at morning, afternoon, and night. Low frequency power (LF) in normalized unites (n.u.) decreased during recovery when compared to exercise, but was still above resting values after 60 minutes of recovery. High frequency power (HF-n.u.) increased after exercise cessation (p < 0.05 for time) and was still below resting values after 60 minutes of recovery. The LF/HF ratio decreased after exercise cessation (p < 0.05 for time), but was still different to baseline levels after 60 minutes of recovery. In conclusion, morning exercise did not delay HR and HRV recovery after light aerobic cycling exercise in sedentary subjects. Additionally, exercise performed in the night did change autonomic control during the sleep. So, it seems that sedentary subjects can engage physical activity at any time of day without higher risk.     

Plasma catecholamine responses to exercise after training with beta-adrenergic blockade

Exercise training has been shown to decrease plasma norepinephrine (NE) and epinephrine (EPI) levels during absolute levels of submaximal exercise, which may reflect alterations in sympathetic tone as a result of training. To determine if beta-adrenergic blockade altered these changes in the plasma concentration of catecholamines with exercise conditioning, we studied the effects of beta-adrenergic blockade on NE and EPI at rest and during exercise in 24 healthy, male subjects after a 6-wk exercise training program. The subjects were randomized to placebo (P), atenolol 50 mg twice daily (A), and nadolol 40 mg twice daily (N). There were no changes in resting NE and EPI compared with pretraining values in any subject group. During the same absolute level of submaximal exercise NE decreased in P and A but was unchanged in N, whereas EPI decreased only in P. At maximal exercise all three groups developed significant increases in NE after training that paralleled increases in systolic blood pressure. EPI at maximal exercise increased after training with N but was unchanged with P or A. These training-induced changes in plasma catecholamine levels were masked or blunted when the A and N groups were studied while still on medication after training. Thus beta-adrenergic blockade has important effects on adaptations of the sympathetic nervous system to training, especially during submaximal exercise.     

Effects of autonomic blockade on cardiac function at rest and during upright exercise in humans

The cardiac function was studied by radionuclide cardiography in eight healthy subjects at rest and during submaximal upright exercise before and after autonomic blockade with metoprolol and atropine. At rest the median stroke volume was reduced by 21% during autonomic blockade (P less than 0.01), but cardiac output was maintained by a concomitant increase in heart rate. The systolic blood pressure was reduced from 120 to 105 mmHg (P less than 0.01), and left ventricular ejection fraction was reduced from 61 to 56% (P less than 0.05). After autonomic blockade the heart rate reached during exercise was the same. Stroke volume and cardiac output were maintained through cardiac dilation. The increase in left ventricular end-diastolic volume was 31 vs. 10% during control conditions (P less than 0.01). The systolic blood pressure was reduced from 174 to 135 mmHg (P less than 0.01). Left ventricular ejection fraction was reduced from 75 to 67% (P less than 0.05), but the increase from rest to exercise was preserved. Total peripheral resistance was reduced by 17% (P less than 0.05). These findings suggest that the heart possesses intrinsic mechanisms to maintain cardiac output during submaximal upright exercise. End-diastolic dilation results in a preserved stroke volume despite a reduced contractility.     

Effects of supramaximal exercise on blood glucose levels during a subsequent exercise

The purpose of the present investigation was to examine the effects of hyperglycemia induced by supramaximal exercise on blood glucose homeostasis during submaximal exercise following immediately after. Six men were subjected to three experimental situations; in two of these situations, 3 min of high-intensity exercise (corresponding to 112, SD 1% VO2max) was immediately followed by either a 60-min period of submaximal exercise (68, SD 2% VO2max) or a 60-min resting period. In the third situation, subjects performed a 63-min period of submaximal exercise only. There were no significant differences between the heart rates, oxygen uptakes, and respiratory exchange ratios during the two submaximal exercise bouts (greater than 15 min) whether or not preceded by supramaximal exercise. The supramaximal exercise was associated within 10 min of the start increases (P less than 0.05) in blood glucose, insulin, and lactate concentrations. This hyperglycemia was more pronounced when subjects continued to exercise submaximally than when they rested (at 7.5 min; P less than 0.05). There was a more rapid return to normal exercise blood glucose and insulin values during submaximal exercise compared with rest. The data show that the hyperinsulinemia following supramaximal exercise is corrected in between 10-30 min during submaximal exercise following immediately, suggesting that this exercise combination does not lead to premature hypoglycemia.     

Exercise responses following ozone exposure.

We have tested the response of 28 subjects to a three-stage ergometer test, with loads adjusted to 45, 60, and 75% of maximum aerobic power following ozone exposure. The subjects were exposed to one of 0.37, 0.50, or 0.75 ppm O3 for 2 h either at rest (R) or while exercising intermittently (IE) (15 min rest alternated with 15 min exercise at approximately 50 W. sufficient to increase VE by a factor of 2.5). Also, all subjects completed a mock exposure VE, respiratory frequency (fR), mixed expired PO2 and PCO2, and electrocardiogram were monitored continuously during the exercise test. Neither submaximal exercise oxygen consumption nor minute ventilation was significantly altered following any level of ozone exposure. The major response noted was an increase in respiratory frequency during exercise following ozone exposure. The increase in fR was closely correlated with the total dose of ozone (r = 0.98) and was accompanied by a decrease in tidal volume (r = 0.91) so that minute volume was unchanged. It is concluded that through its irritant properties, ozone modifies the normal ventilatory response to exercise, and that this effect is dose dependent.     

Effects of increased training load on vagal-related indexes of heart rate variability: a novel sleep approach

There is little doubt that moderate training improves cardiac vagal activity and thus has a cardioprotective effect against lethal arrhythmias. Our purpose was to learn whether a higher training load would further increase this beneficial effect. Cardiac autonomic control was inferred from heart rate variability (HRV) and analyzed in three groups of young subjects (24.5 +/- 3.0 yr) with different training states in a period free of stressful stimuli or overload. HRV was analyzed in 5-min segments during slow-wave sleep (SWS, a parasympathetic state that offers high electrocardiographic stationarity) and compared with data collected during quiet waking periods in the morning. Sleep parameters, fatigue, and stress levels checked by questionnaire were identical for all three groups with no signs of overtraining in the highly trained (HT) participants. During SWS, a significant (P <0.05) increase in absolute and normalized vagal-related HRV indexes was observed in moderately trained (MT) individuals compared with sedentary (Sed) subjects; this increase did not persist in HT athletes. During waking periods, most of the absolute HRV indexes indistinctly increased in MT individuals compared with controls (P < 0.05) but did not increase in HT athletes. Normalized spectral HRV indexes did not change significantly among the three groups. Heart rate was similar for MT and Sed subjects but was significantly (P <0.05) lower in HT athletes under both recording conditions. These results indicate that SWS discriminates the state of sympathovagal balance better than waking periods. A moderate training load is sufficient to increase vagal-related HRV indexes. However, in HT individuals, despite lower heart rate, vagal-related HRV indexes return to Sed values even in the absence of competition, fatigue, or overload.     

Ventilation during sleep onset

There is now considerable evidence which indicates that respiratory activity is different during sleep compared with wakefulness. However, there has been little work on respiratory changes during the transitional period from wakefulness to sleep. The present study was concerned with the quantitative and temporal properties of ventilation during sleep onset. Sleep onsets were studied in five young male adults in a series of single-subject designs in which sleep onsets were replications. The results indicated that during sleep onset the loss of alpha-activity in the electroencephalogram was associated with a substantial, rapid, and highly predictable reduction in ventilation. The change in ventilation was typically due to a reduction in tidal volume and was, in part, secondary to a reduction in metabolic rate. We speculate that the nonmetabolic component may reflect the loss of waking neural drive to respiration, though the present study did not eliminate a variety of other interpretations.     

Respiration During Sleep in Children

In 22 children (11 boys and 11 girls), aged 9 to 13 years, respiration was monitored during one night of sleep. No child had a significant history of breathing problems during sleep. Sleep was recorded using standard techniques (electroencephalography, electrooculography, electromyography), and respiration was measured with nasal thermistors and abdominal or thoracic strain gauges. Respiratory pauses (five seconds or longer) were determined for all sleep stages. Respiratory rate was scored only in the first and last sleep cycles and during ten waking minutes before sleep onset. Respiratory rate was significantly affected by wakefulness or stage of sleep: highest in wakefulness and stage 1, lowest in stage 2 of the last sleep cycle. Regularity of respiratory rate showed a similar effect. Variance of respiratory rate was significantly lower in girls than boys. Respiratory pauses during sleep were seen in every child, ranging from 3 to 40 pauses per night (average, 17.2 for boys and 18.0 for girls). Significantly greater numbers of pauses per minute were seen in stage 1 and rapid eye movement (REM) sleep than in stages 2, 3 and 4. The longest respiratory pause was 25 seconds. The conclusion is made that a small number of respiratory pauses during sleep are normal in children of this age.     

The effects of sleep deprivation and time of day on cognitive performance

The extent to which the diurnal fluctuations of different cognitive processes could be affected by sleep loss may be explored to predict performance decrements observed in the real world. Twenty healthy male subjects voluntarily took part in 8 test sessions at 06:00, 10:00, 14:00, and 18:00 h, following either a night with or without sleep in random order. Measurements included oral temperature, simple reaction time, sign cancelation, Go/NoGo, and the Purdue pegboard test. The results indicate that simple reaction time and motor coordination had morning–afternoon variations closely following the rhythms of temperature and vigilance. Inhibitory attention (Go/NoGo) presented no morning–afternoon variations. Sleep deprivation may affect the profiles of cognitive performance depending on the processes solicited. Sustained and inhibitory attention are particularly affected in the morning (after 24 and 28 waking hours), while a complex task (visuo-motor coordination) would be affected after 32 waking hours only.     

Comparison of hyperthermic hyperpnea elicited during rest and submaximal, moderate-intensity exercise.

We tested the hypothesis that, in humans, hyperthermic hyperpnea elicited in resting subjects differs from that elicited during submaximal, moderate-intensity exercise. In the rest trial, hot-water legs-only immersion and a water-perfused suit were used to increase esophageal temperature (T(es)) in 19 healthy male subjects; in the exercise trial, T(es) was increased by prolonged submaximal cycling [50% peak O(2) uptake (Vo(2))] in the heat (35 degrees C). Minute ventilation (Ve), ventilatory equivalent for Vo(2) (Ve/Vo(2)) and CO(2) output (Ve/Vco(2)), tidal volume (Vt), and respiratory frequency (f) were plotted as functions of T(es). In the exercise trial, Ve increased linearly with increases (from 37.0 to 38.7 degrees C) in T(es) in all subjects; in the rest trial, 14 of the 19 subjects showed a T(es) threshold for hyperpnea (37.8 +/- 0.5 degrees C). Above the threshold for hyperpnea, the slope of the regression line relating Ve and T(es) was significantly greater for the rest than the exercise trial. Moreover, the slopes of the regression lines relating Ve/Vo(2), Ve/Vco(2), and T(es) were significantly greater for the rest than the exercise trial. The increase in Ve reflected increases in Vt and f in the rest trial, but only f in the exercise trial, after an initial increase in ventilation due to Vt. Finally, the slope of the regression line relating T(es) and Vt or f was significantly greater for the rest than the exercise trial. These findings indicate that hyperthermic hyperpnea does indeed differ, depending on whether one is at rest or exercising at submaximal, moderate intensity.     

From slow waves to sleep homeostasis: new perspectives

EEG slow waves are the epitome of deep nonREM sleep. The level of slow-wave activity (SWA; defined as spectral power in the 0.5-4.5 Hz band) in the initial part of sleep is determined by prior sleep and waking, and thereby represents a marker of a homeostatic sleep regulating process (Process S). Models based on SWA were successful in simulating sleep architecture in a variety of experimental protocols. SWA is an exceptional sleep variable in that it is little influenced by circadian phase and variations of the photoperiod. There is recent evidence that it is not waking per se but the absence of sleep, which engenders a rise in sleep propensity. Thus animals emerging from the hypometabolic states of hibernation or daily torpor exhibit an increase in SWA akin to sleep deprivation. Recent human studies showed SWA to be a marker of a local, use-dependent facet of sleep. Selective activation of specific cortical areas during waking enhanced SWA over the activated region during sleep. A frontal predominance of power in the 2-Hz band was documented in the initial part of a normal sleep episode. Sleep homeostasis may be a valuable concept for exploring the evolutionary origin of sleep. Thus 'rest homeostasis' has been demonstrated in invertebrate species, and the search for homologies of rest and sleep on a molecular genetic level has begun. Conceptualizing and characterizing sleep as a regulated process may eventually shed light on its function.     

Forearm metabolic asymmetry detected by 31P-NMR during submaximal exercise

This study evaluated the relationship of skeletal muscle energy metabolism to forearm blood flow and muscle mass in the dominant (D) and nondominant (ND) forearms of normal subjects. 31P-Magnetic resonance spectroscopy was used to determine intracellular pH and the ratio of inorganic phosphate to phosphocreatine (Pi/PCr), an index of energy metabolism. Forearm blood flow and muscle mass were measured by venous occlusion plethysmography and magnetic resonance imaging, respectively. Metabolic measurements and flow were determined at rest and during submaximal exercise in both forearms. After a warm-up period, six normal right-handed male subjects performed 7.5 min of wrist flexion exercise in the magnet (1 contraction every 5 s), first with the ND forearm and then with the D forearm, at 23, 46, and 69 J/min. At rest, there were no differences between forearms in Pi/PCr or pH. However, at each work load the D forearm demonstrated significantly lower Pi/PCr and higher pH than the ND forearm. Blood flow was not significantly different between the forearms at rest or during exercise. Because these subjects were not engaged in unilateral arm training, we conclude that 1) Pi/PCr is lower and pH is higher in the D compared with the ND forearm in normal subjects during submaximal exercise, 2) these differences are independent of muscle mass and blood flow, and 3) the cumulative effect of long-term, low-level daily activity provides an adequate training stimulus for muscular metabolic adaptations.     

State influences on ventral medullary surface and physiological responses to sodium cyanide challenges.

Intravenous sodium cyanide (NaCN) administration lowers ventral medullary surface (VMS) activity in anesthetized cats. Sleep states modify spontaneous and blood pressure-evoked VMS activity and may alter VMS responses to chemoreceptor input. We studied VMS activation during peripheral chemoreceptor stimulation by intravenous NaCN using optical procedures in six cats instrumented for recording sleep physiology during sham saline and control site trials. Images of scattered 660-nm light were collected at 50 frames/s with an optical device after 80-100 microg total bolus intravenous NaCN delivery during waking and sleep states. Cyanide elicited an initial ventilatory decline, followed by large inspiratory efforts and an increase in respiratory rate, except in rapid eye movement sleep, in which an initial breathing increase occurred. NaCN evoked a pronounced decrease in VMS activity in all states; control sites and sham injections showed little effect. The activity decline was faster in rapid eye movement sleep, and the activity nadir occurred later in waking. Sleep states alter the time course but not the extent of decline in VMS activity.     

Effects of sleep pressure on endogenous cardiac autonomic activity and body temperature.

This study investigated the effects of variations in sleep pressure on cardiac autonomic activity and body temperature. In a counterbalanced design, 12 healthy, young subjects (6 men and 6 women) remained recumbent during 30 h of wakefulness (high sleep pressure) and 6 h of wakefulness (low sleep pressure). Both periods of wakefulness were immediately followed by a sleep opportunity, and the first 2 h of sleep were analyzed. During extended hours of wakefulness, a reduction in heart rate was mediated by a decline in cardiac sympathetic activity (measured via preejection period) and the maintenance of cardiac parasympathetic activity (measured via respiratory sinus arrhythmia). In subsequent high-pressure sleep, parasympathetic activity was amplified and sympathetic activity was negatively associated with electroencephalographic slow-wave activity. Sleep deprivation had no impact on foot temperature, but it did alter the pattern of change in core body temperature. A downregulation of cardiac autonomic activity during both extended hours of wakefulness and subsequent sleep may respectively provide "protection" and "recovery" from the temporal extension of cardiac demand.     

Autonomic nervous control of postprandial hemodynamic changes at rest and upright exercise

Postprandial hemodynamic changes were studied in healthy subjects at rest and during exercise in the upright position with and without autonomic blockade of the heart. At rest cardiac output increased 61% mostly because of a stroke volume increase accomplished by left ventricular end-diastolic dilation. These changes seemed to be dependent on the autonomic nervous system, whereas the postprandial heart rate increase did not. During exercise cardiac output was 23% higher after food intake due to a rise in both stroke volume and heart rate. These changes were apparently under influence of the autonomic nervous system, whereas left ventricular dilation was not. The present findings indicate that most of the postprandial changes in the central circulation are under control of the autonomic nervous system.     

Evaluation of left ventricular diastolic function at rest and during exercise by gated radionuclide angiocardiography in coronary artery disease patients

The peak filling rate (PFR) is an index of the diastolic function and has been proposed as an excellent parameter for the evaluation and early detection of left ventricular (LV) dysfunction. This study contributes to the assessment of LV diastolic function at rest and during submaximal exercise in 19 normal subjects and in 42 patients with coronary artery disease (CAD). The PFR was compared to the ejection fraction (EF) and the peak ejection rate (PER)--both indexes of systolic LV function--after acquiring a high-resolution time-activity curve (time/frame between 10 and 30 msec) with gated radionuclide angiocardiography. In 23 patients with normal EF at rest (greater than or equal to 50%), PFR and PER were abnormally low in 87% and 43% of the cases respectively. During submaximal exercise in 13 CAD patients, EF, PFR and PER varied very little from baseline values but were significantly reduced compared to the values of normal subjects. The PFR proved to be a very sensitive indicator of LV dysfunction in coronary patients but was not capable of discriminating between one-, two- or three-vessel disease. Our results tend to show the PFR to be a good indicator of LV dysfunction at rest and during exercise and its usefulness for the assessment of LV function is becoming more and more evident in clinical practice.