[Biologic rhythms: their changes in night-shift workers]. / Les rythmes biologiques: leur altération chez les travailleurs de nuit.

ENVIRONMENTAL STRESS: Environmental cycles, such as the light-dark cycle, provide information used by the biological clock in the hypothalamus to synchronize the biological systems and maintain the organism's internal cohesion. In persons whose work schedules include night hours (approximately 20% of the working population in France) the sleep-wake cycles are not in phase with these environmental cycles. BIOLOGICAL RHYTHMS: What effect does the conflicting information perceived by night-shift workers have on their biological rhythms? Indices of the processes going on in the cerebral clock, these biological rhythms are the only tool available in man to determine possible dysfunction of the clock. Several studies have identified these rhythms in night-shift workers but results have been contradictory. PARTIAL ADAPTATION: Recently we made repeated measurements every 10 min over a 24 hour period in night-shift workers to determine the precise melatonin, cortisol, and thyrotropin (TSH) patterns, which reflect the endogenous clock, and prolactin (PRL) and growth hormone (GH) patterns which are influenced by sleep but also have a circadian component. This study demonstrated that there is some, but partial, adaptation of the biological rhythms in these persons. The shift in the melatonin pattern is quite variable from one individual to another. Night work causes a distortion in the cortisol and TSH rhythms. This partial adaptation is also seen in the GH and PRL curves, mainly related to sleep, but whose endogenous component previously described in other experimental situations is found in night workers with a distribution incompletely adapted to the secretory episodes. RESEARCH PERSPECTIVES: Both daytime sleep and night-time work are associated with perturbed endocrine functions which could explain certain health problems and sleep disorders observed (or avowed) after several years of night-shift work. These problems require further research into factors susceptible of resynchronizing the biological clock.

Endothelin participates in increased circulating atrial natriuretic peptide early after human heart transplantation.

BACKGROUND: Hemodynamic improvement after heart transplantation is expected to normalize the neuroendocrine balance, but circulating atrial natriuretic peptide (ANP) remains elevated. Endothelin stimulates ANP secretion and its concentration increases after heart transplantation, suggesting a role for this peptide in the cardiovascular adaptative response to heart transplantation. METHODS: To investigate whether endothelin may induce ANP increase in heart transplant recipients, we monitored daily ANP, endothelin, and related hormonal, biologic, and hemodynamic parameters before and during the first week after either heart transplantation (n = 15) or coronary artery bypass grafting (n = 10). RESULTS: Surgery induced a transient secretory peak of arginine vasopressin and endothelin in both groups at day 1. Bypass grafting did not modify normal ANP (11.8 +/- 2.1 pmol/L), endothelin (2.4 +/- 0.3 pmol/L), renin activity (0.11 +/- 0.04 pmol/L/sec), or aldosterone (492 +/- 122 pmol/L) values. Heart transplantation normalized the renin-aldosterone axis, but the early decrease observed for ANP (from 27.2 +/- 4.8 to 21.14 +/- 1.4 pmol/L) was only partial and transient. Endothelin further increased (from 4.4 +/- 0.8 to 9.14 +/- 1.8 pmol/L; p < 0.01) after transplantation. Positive correlations were observed between endothelin, isoproterenol dose, creatinine, right atrial pressure, and ANP, but multiple correlation analysis showed the important role of endothelin (r = 0.69, p < 0.001). Cyclic guanosine monophosphate correlated with ANP (r = 0.65, p < 0.001). CONCLUSIONS: Elevated endothelin, suggesting vascular dysfunction, likely contributes to the ANP increase observed early after heart transplantation. Furthermore, ANP, through a cardiac endothelium feedback, may act in the maintenance of circulatory homeostasis in heart transplant recipients.

Temporal relationships between pulsatile cortisol secretion and electroencephalographic activity during sleep in man.

A temporal link between slow wave sleep and low or decreasing cortisol release has been previously demonstrated. This relationship was re-evaluated in 15 healthy male subjects using spectral analysis of their sleep electroencephalogram (EEG). EEG activity in the delta, theta, alpha and beta bands was cross-correlated with cortisol secretory rates at 10-min intervals. For the period of pulsatile cortisol secretion, an inverse relationship was found with the delta band with an average cross-correlation coefficient of -0.505 (P < 0.0001). Variations in cortisol secretory rates coincided with or anticipated opposite variations in delta wave activity by 10 or 20 min. A significant positive correlation was found with theta activity, but alpha and beta bands did not elicit any systematic association with cortisol profiles. These results demonstrate a temporal association between cortisol secretory pulses and delta wave activity in man, suggesting the existence of a central control common to both variables.

Twenty-four-hour melatonin and core body temperature rhythms: their adaptation in night workers.

To determine whether the melatonin (MT) rhythm is adapted to a permanent nocturnal schedule, 11 night workers were studied during their usual 24-h cycle, and 8 day-active subjects during two 24-h cycles, once with night sleep and once after an acute shift of their sleep period to daytime. Rectal temperature (Tre) was continuously recorded. In day-active subjects, the MT rhythm was not affected by the acute shift in the sleep period, whereas the Tre rhythm was split in a biphasic pattern with the circadian descending phase during the night of sleep deprivation and a second descending trend during day sleep. Night workers showed a great variability in their MT profiles, with the onset of the MT release varying between 2145 and 0505. In contrast, the Tre rhythm was homogeneously entrained to their usual sleep-wake cycle, with the onset of the descending trend initiated before sleep onset so that the large decrease was found, in some subjects, to be uncoupled with their MT increase. The night-active schedule did not induce any amplitude modification of the Tre and the rhythms compared with day-active subjects sleeping at night. No relationship between work-dependent factors and the extent of the MT shift could be found. These results show the great variability in the timing of MT secretion among night workers, in contrast to the homogeneity of their Tre rhythm. The exact mechanisms by which night workers adapt their circadian systems have not yet been identified.

Growth hormone secretion in night workers.

We previously reported that, in night workers, cortisol and TSH rhythms, known to have a high endogenous component, adapted only partially to the nocturnal schedule. The aim of the present study was to investigate the degree of adaptation of the growth hormone (GH) rhythm, considered to be mainly sleep-dependent, but for which a weak circadian drive has also been suggested. Eleven night workers were studied during their usual sleep-wake cycle, and two groups of 11 normally day-active subjects, sleeping once during the night and once after an 8-h sleep delay, were used as control groups. GH secretory rates were calculated by deconvolution of the plasma concentrations analyzed at 10-min intervals. The total amount of GH secreted during the 24 h did not differ between the three groups and the main secretory episode occurred, in most cases, during the first half of the sleep period. In night sleepers and night workers the enhanced amount of GH secreted at that time was followed by a significantly lower amount secreted during the second part of the sleep period (p < 0.001 and p < 0.05, respectively). For night sleepers, an enhanced GH pulse frequency was found at the beginning of sleep, whereas for night workers and day sleepers the pulses were distributed more randomly throughout the nychthemeron. After an abrupt sleep shift, all the subjects displayed a GH pulse at the usual time of early sleep, but such a pulse was present in only 8 of 11 night workers. Thus the amount of GH secreted between 23:00 h and 03:00 h in day sleepers did not differ significantly from that observed in night sleepers, whereas it differed for night workers. These results confirm the considerable influence of sleep in driving the GH rhythm and the existence of a circadian influence revealed by an acute shift in the sleep period. They also provide evidence of an incomplete adjustment of GH rhythms in night workers.

A quantitative evaluation of the relationships between growth hormone secretion and delta wave electroencephalographic activity during normal sleep and after enrichment in delta waves.

The existence of a relationship between growth hormone (GH) release and slow-wave sleep (SWS), often studied in the past using conventional scoring of sleep stages, remains controversial. In the present study, this relationship was reevaluated by spectral analysis of the sleep electroencephalogram (EEG) and deconvolution analysis of the plasma GH concentrations during normal nocturnal sleep and after enrichment in SWS by means of ritanserin, a selective 5-HT2 receptor antagonist. Eight healthy male subjects each participated in two randomized night studies after having received either a placebo or a 5-mg dose of ritanserin. They were subjected to 8 hours of polysomnography, including spectral analysis of the sleep EEG. Plasma GH levels were measured at 10-minute intervals. The mean delta absolute power and the mean GH secretory rates were significantly higher under ritanserin than under placebo for the first 3 hours after sleep onset (+24% and +29%, respectively). Their nocturnal profiles were significantly and positively correlated in all subjects (average r = 0.710 under placebo, 0.567 under ritanserin; p < 0.0001 in both cases). GH secretory pulses were found to be coincident with delta activity peaks in both directions. The amount of GH secreted during significant GH pulses was correlated with the amount of concomitant delta wave activity (r = 0.803 under placebo, r = 0.764 under ritanserin, p < 0.0001). Similarly, the amount of delta wave activity found during delta wave peaks was correlated with the amount of GH secreted concomitantly (r = 0.715 under placebo, r = 0.723 under ritanserin: p < 0.0001). These results demonstrate a close temporal and quantitative relationship between GH secretion and delta wave activity, which may be evidence of common stimulatory mechanisms.

Twenty-four-hour prolactin profiles in night workers.

In addition to sleep processes, it has been suggested that an intrinsic circadian rhythmicity is involved in the temporal organization of prolactin (PRL) secretion. Eight night workers were studied to determine whether the PRL rhythm is adapted to their rest-activity schedule and whether this provides evidence in favor of an endogenous clock-driven component. Ten day-active subjects, sleeping once during the night and once after an 8-h delay in their sleep period, were used as a control group. Plasma PRL, body temperature, and plasma melatonin were measured at 10-min intervals. Twenty-four-hour PRL profiles did not differ between night workers sleeping as usual during the daytime and day-active subjects submitted to an abrupt sleep shift to daytime. For the two groups of subjects a transient PRL peak, similar in size and time of occurrence, was observed during the night. Melatonin, a strong marker of the primary circadian oscillator, displayed a phase shift that differed widely among night workers. Body temperature, on the other hand, was found to be more regularly adapted despite the persistence of a small decrease or leveling off during the night. Although no relationship was found between the melatonin increase and the nocturnal PRL peak, a concomitance with this transient temperature decrease could be demonstrated. The persistence of this PRL peak in night workers raises the question of its significance.

5-HT2 receptors are partially involved in the relationship between renin release and delta relative power.

A strong relationship was previously described between the nocturnal oscillations of plasma renin activity (PRA) and the sleep cycles, with levels of PRA that increase during non rapid eye movement sleep and decrease during rapid eye movement sleep. This study was designed to determine whether ritanserin, a 5-hydroxytryptamine-2 (5-HT2) receptor antagonist known to increase slow wave sleep both in human and in animals and to decrease plasma renin activity response to serotonergic stimulation in the rat, would uncouple this relationship. Eight subjects underwent two randomized night studies after having received either placebo or 5 mg ritanserin administered in the morning. They were subjected to 8 hour polysomnography, including spectral analysis of the electroencephalogram and to continuous blood sampling. Blood was sampled from 2300 to 700h every 10 min and plasma renin activity (PRA) was measured by radioimmunoassay of angiotensin 1. The nocturnal profiles were analysed using the pulse detection program ULTRA. Ritanserin produced the expected increase in slow wave sleep (SWS) duration (132 +/- 10 min under ritanserin vs 72 +/- 9 min under placebo; p < 0.001) and a significant increase in delta relative power (69 +/- 2% under ritanserin vs 60 +/- 2% under placebo; p < 0.01). The mean overnight PRA levels had a tendency to decrease under ritanserin (1.66 +/- 0.34 ngAngl/ml per h under ritanserin vs 1.48 +/- 0.31 ngAngl/ml per h under placebo; p = 0.08). Individual PRA oscillations were preserved and remained strongly associated with delta power oscillations. PRA peak levels were similar in both experimental conditions, but the absolute amplitude of the oscillations was decreased under ritanserin (1.50 +/- 0.36 ngAngl/ml per h vs 1.04 +/- 0.14 ngAngl/ml per h; p < 0.05). These results demonstrate that ritanserin, at a dose that augments delta power, only weakly affects renin release, which suggests that 5-HT2 receptors are only partially involved in the processes coupling renin release and SWS and that other mechanisms probably control the sleep-associated variations in PRA.

Internal dissociation of the circadian markers of the cortisol rhythm in night workers.

To determine whether the circadian system of night workers is adapted to a night-active schedule, we submitted 11 night workers and 11 day-active subjects to a 10-min blood sampling procedure during their usual sleep-wake cycle, permitting a precise determination of circadian and ultradian cortisol variations. In night works, the usual shift of 8 h in the sleep period was associated with a distortion of the normal 24-h cortisol rhythm. The acrophase exhibited a shift of approximately 6.5 h, whereas the quiescent period, abruptly interrupted by a large peak, underwent a shift of only 3 h and lasted for approximately 5 h, as in day-active subjects. Slow-wave sleep and sleep onset occurred during periods of low or decreasing cortisol secretory rates, whereas awakenings were associated with an increase in cortisol secretory rates. These results revealed that the circadian system of night workers only partially adapts to night work and that adaptation processes rely on an internal dissociation of the markers of the cortisol pattern, without disturbing the processes that couple cortisol release and specific sleep stages.

Atrial natriuretic factor secretion: a role for atrial systolic ejection force?

The increase in plasma concentration of atrial natriuretic factor in heart transplant patients has not been fully elucidated. Besides an eventual pressure or volume overload leading to passive atrial distension, the atrial tension developed during atrial systole, or atrial ejection force, which may be increased by the transplantation procedure, is an important determinant of atrial natriuretic factor release. We therefore determined the plasma concentration of atrial natriuretic factor and the maximal atrial ejection force in 15 heart transplant patients and 8 controls, matched for age and body mass. Atrial ejection force, as defined as the force exerted by the left atrium to accelerate blood into the left ventricle during atrial systole, was obtained using combined two-dimensional imaging and doppler echocardiography. Serum creatinin concentrations, heart rate [91.9 (SD 13.2) vs 71.8 (SD 10.9) beats.min-1], mean arterial blood pressure [103.9 (SD 9.8) vs 87.4 (SD 5.8) mmHg, 13.85 (SD 1.31) vs 11.65 (SD 0.77) kPa], left ventricular posterior wall thickness and interventricular septum thickness were higher in heart transplant patients compared to controls. Plasma concentration of atrial natriuretic factor was also elevated in heart transplant patients [63.9 (SD 18.1) vs 34.0 (SD 3.2) pg.ml-1; P < 0.001]. In contrast, although the left atrial area was greater in heart transplant patients [28.2 (SD 4.8) vs 15.8 (SD 2.5) cm2; P < 0.001], mitral area, transmitral Doppler A-wave maximal velocity and atrial ejection force were similar in transplant and in control patients [7.7 (SD 3.5) vs 8.9 (SD 2.8) kdyn, 77 (SD 35) vs 89 (SD 28)mN]. No significant correlation was observed between concentration of atrial natriuretic factor and atrial ejection force, either in heart transplant patients or in controls. Thus, the elevated plasma concentration of atrial natriuretic factor observed in these heart transplant patients was multifactorial in origin, and was considered to depend upon an hypersecretion rather than upon a decreased clearance rate. Moreover, it is suggested that the atrial ejection force was unlikely to have participated in this enhanced release of atrial natriuretic factor.

Effect of short-term endurance training on exercise capacity, haemodynamics and atrial natriuretic peptide secretion in heart transplant recipients.

Exercise tolerance of heart transplant patients is often limited. Central and peripheral factors have been proposed to explain such exercise limitation but, to date, the leading factors remain to be determined. We examined how a short-term endurance exercise training programme may improve exercise capacity after heart transplantation, and whether atrial natriuretic peptide (ANP) release may contribute to the beneficial effects of exercise training by minimizing ischaemia and/or cardiac and circulatory congestion through its vasodilatation and haemoconcentration properties. Seven heart transplant recipients performed a square-wave endurance exercise test before and after 6 weeks of supervised training, while monitoring haemodynamic parameters, ANP and catecholamine concentrations. After training, the maximal tolerated power and the total mechanical work load increased from 130.4 (SEM 6.5) to 150.0 (SEM 6.0) W (P < 0.05) and from 2.05 (SEM 0.1) to 3.58 (SEM 0.14) kJ.kg-1 (P < 0.001). Resting heart rate decreased from 100.0 (SEM 3.4) to 92.4 (SEM 3.5) beats.min-1 (P < 0.05) but resting and exercise induced increases in cardiac output, stroke volume, right atrial, pulmonary capillary wedge, systemic and pulmonary artery pressures were not significantly changed by training. Exercise-induced decrease of systemic vascular resistance was similar before and after training. After training arterio-venous differences in oxygen content were similar but maximal lactate concentrations decreased from 6.20 (SEM 0.55) to 4.88 (SEM 0.6) mmol.l-1 (P < 0.05) during exercise. Similarly, maximal exercise noradrenaline concentration tended to decrease from 2060 (SEM 327) to 1168 (SEM 227) pg.ml-1. A significant correlation was observed between lactate and catecholamines concentrations. The ANP concentration at rest and the exercise-induced ANP concentration did not change throughout the experiment [104.8 (SEM 13.1) pg.ml-1 vs 116.0 (SEM 13.5) pg.ml-1 and 200.0 (SEM 23.0) pg.ml-1 vs 206.5 (SEM 25.9) pg.ml-1, respectively]. The results of this study suggested that the significant improvement in exercise capacity observed after this short-term endurance training period may have arisen mainly through peripheral mechanisms, associated with the possible decrease in plasma catecholamine concentrations and reversal of muscle deconditioning and/or prednisone-induced myopathy.

Temporal link between plasma thyrotropin levels and electroencephalographic activity in man.

Plasma thyrotropin (TSH) levels have been previously shown to be associated with the internal sleep structure determined by conventional scoring of sleep stages. This temporal relationship was re-evaluated using spectral analysis of the sleep electroencephalogram (EEG). Eight healthy male subjects underwent two randomized night studies after having received either placebo or 5 mg ritanserin, a selective 5-HT2 receptor antagonist known to increase slow-wave sleep. Delta relative power and TSH levels, determined at 10 min intervals, were found to be inversely related with an average cross-correlation coefficient highly significant (P < 0.0001) in both experimental conditions. Alpha slow-wave index, an estimator of awakenings, and TSH pulses exhibited a significant temporal association in both conditions. These results demonstrate that TSH fluctuations are linked to the sleep EEG activity in man.

Slow wave electroencephalic activity parallels renin oscillations during sleep in humans.

Previous studies have demonstrated that the nocturnal oscillations of plasma renin activity (PRA) exactly reflect rapid eye movement (REM) non-REM (NREM) sleep alternation with levels of PRA that increase during NREM sleep and decrease during REM sleep. These studies were based exclusively on conventional scoring of sleep stages. In the present study, we used spectral analysis of the sleep EEG to determine the variations in the different EEG frequency bands, together with PRA profiles. Eight male volunteers participated in a 1 night study. They were subjected to 8 h polysomnography including spectral analysis of the EEG, and to blood sampling every 10 min. Delta relative power and Sleep Intensity Index and PRA oscillations ran parallel in all individuals. An increase in slow waves was associated with an increase in PRA, whereas a decrease was associated with a decrease in PRA. Cross-correlation coefficients were significant and ranged between 0.34 and 0.74. Conversely, theta, alpha and beta bands and the EEG mean frequency were inversely proportional to PRA, with lower cross-correlation coefficients. These results may give further support to the hypothesis of a common mechanism controlling both SWA and renin release from the kidney.

Temporal relationship between prolactin secretion and slow-wave electroencephalic activity during sleep.

It is well established that plasma prolactin (PRL) concentrations exhibit a sleep-dependent pattern, with the highest levels occurring during sleep and the lowest during waking. Still, controversy exists concerning an association between rapid eye movement (REM) and non-REM sleep cycles and plasma PRL pulses. These studies were all based on conventional scoring of sleep stages. In the present study, plasma PRL concentrations were analyzed at 10-minute intervals in 10 subjects during the night when sleeping. PRL secretory rates were calculated by a deconvolution procedure. Spectral parameters of sleep electroencephalographic (EEG) recordings were analyzed together with PRL secretion using cross-correlation. Slow-wave activity of the EEG and PRL secretion ran parallel in all individuals. Conversely, alpha and beta bands and the EEG mean frequency were inversely proportional to PRL secretion. In 9 of the 10 subjects studied, PRL secretion was concomitant with delta waves or lagged behind by 10-20 minutes, depending on subjects, with maximum cross-correlation coefficients ranging between 0.40 and 0.67. This temporal relationship between PRL secretion and delta waves was further assessed by a pulse-by-pulse analysis based on the calculation of probability levels after computer simulations. Nine of the 10 subjects displayed significant concomitance between delta wave activity and PRL secretory oscillations. These results demonstrate that PRL secretion during sleep is coupled to delta waves in young healthy men.

Comparative effect of night and daytime sleep on the 24-hour cortisol secretory profile.

To determine whether cortisol secretion interacts with daytime sleep in a similar manner to that reported for night sleep, 14 healthy young men were studied during two 24-hour cycles. During one cycle they slept during the night, during the other the sleep period was delayed by 8 hours. Secretory rates were calculated by a deconvolution procedure from plasma cortisol, measured at 10-minute intervals. The amount of cortisol secreted during night sleep was lower than during the corresponding period of sleep deprivation (12.7 +/- 1.1 vs. 16.3 +/- 1.6 mg; p < 0.05), but daytime sleep beginning at the habitual time of morning awakening failed to inhibit cortisol secretion significantly. There was no difference between the amount of cortisol secreted from 0700 to 1500 hours in sleeping subjects and in subjects who were awake during the same period of time (24.2 +/- 1.5 vs. 22.5 +/- 1.4 mg). Even if the comparison between sleeping and waking subjects was restricted to the period 0700-1100 hours or 0700-0900 hours, no significant difference was found. Neither secretory pulse amplitude nor frequency differed significantly in either period. However, detailed analysis of the secretory rates in day sleepers demonstrated a transient decrease in cortisol secretion at about the time of sleep onset, which began 10 minutes before and lasted 20 minutes after falling asleep. Spontaneous or provoked awakenings had a determining influence on the secretory profiles. Ten to 20 minutes after awakening from either night or day sleep cortisol secretion increased significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Distinct modes of melatonin secretion in normal men.

As for many hormones, melatonin levels in the blood suggest that it is discharged from the pineal gland in a pulsatile manner. Recently, the existence of short-term episodes, superimposed on the circadian pattern of circulating melatonin, has been questioned. Because plasma melatonin levels reflect not only the secretory process, but also the effects of distribution and degradation, secretory rates were estimated from peripheral levels, using a deconvolution procedure. Fourteen healthy volunteers were studied during the night, while sleeping in the dark (2300-0700), and seven of them subsequently were used in a replicate study. Plasma melatonin levels were measured at 10-min intervals by a direct, specific radioimmunoassay. Pulse analysis was performed using the computer program ULTRA. Approximately 30% more pulses were detected on the overall secretory were often superimposed on tonic basal secretion. Their number, amplitude, and distribution over time were variable depending on subjects. Also the mean melatonin secretory rate varied more than threefold across individuals. Despite the large interindividual variability, the subjects, who were used in replicate experiment, displayed a rather similar secretory profile. We conclude that in normal adult men, melatonin secretion undergoes two distinct secretory modes, in which episodic secretion is superimposed on tonic secretion in subject-dependent variable proportions.

The circadian thyrotropin rhythm is delayed in regular night workers.

In order to determine whether the circadian thyrotropin (TSH) rhythm is adapted to a night-active schedule, plasma TSH and body temperature were measured for 28 h every 10-min in 8 regular night workers and in 8 day-active subjects. In night workers, the shift of 8-h in the sleep period induced a mean shift of 6 h 30 min of the TSH acrophase which remained located, as in day-active subjects, at about the time of sleep onset. The nadir of the body temperature rhythm was shifted by an equivalent amount and occurred systematically during the sleep period, so that both parameters maintained a fixed phase relationship. TSH and temperature rhythms had similar amplitudes in the two groups. However, mean TSH values in night workers returned more rapidly to basal values. These results demonstrate that, together with body temperature, TSH acrophase is adapted to regular night work, suggesting that TSH may be a good index for evaluating the orientation of the endogenous clock.

Prolactin secretion during sleep in obstructive sleep apnoea patients.

Plasma prolactin (PRL) concentration exhibits a sleep-dependent pattern, with highest levels during sleep and lowest levels during the waking period. The syndrome of obstructive sleep apnoea (OSA) is associated with severe hypoxaemia and chronic sleep fragmentation, both of which could affect the sleep-entrained PRL rhythm. Treatment with nasal continuous positive airway pressure (CPAP) immediately restores a normal sleep structure by successful abolition of the apnoeas. In the present study, seven OSA patients underwent two night studies, once when no treatment was given and once during the first night of CPAP treatment. Sleep was recorded polygraphically in all experiments. Plasma PRL was measured at 10 min intervals and secretory rates were calculated by a deconvolution procedure. CPAP treatment greatly reduced hypoxaemia and improved sleep quality. The secretory pulse amplitude and the total amount of PRL secreted during the night remained constant regardless of whether patients were treated or not. The only difference found was a lower pulse frequency in untreated OSA patients as compared to treated patients, which may be attributed either to hypoxaemia or to sleep disturbance or to the combined action of both. Treatment may be considered to normalize PRL release by restoring pulse frequency to values similar to those observed for normal subjects.

Slow oscillations of plasma glucose and insulin secretion rate are amplified during sleep in humans under continuous enteral nutrition.

Concomitant oscillations of plasma glucose and insulin secretion rate with a periodicity of about 80 minutes have been identified in normal humans. To determine whether these slow oscillations are influenced by sleep, peripheral levels of glucose and C-peptide were measured at 10-minute intervals over 24 hours in seven subjects, once with a normal nocturnal sleep from 2300 to 0700 hours, and once with a shifted daytime sleep from 0700 to 1500 hours. The subjects received continuous enteral nutrition and remained supine for the 8 hours preceding blood sampling and throughout the whole experiment. Insulin secretion rate was estimated by deconvoluting peripheral C-peptide levels using an open two-compartment model. The amplitude of glucose and insulin secretion rate oscillations increased by 160% during the 8-hour sleep periods, at whatever time they occurred, whereas the influence of the time of day was not significant. Glucose and insulin secretion rate mean levels were also significantly increased during normal nocturnal sleep compared to the remaining 8-hour waking periods, but this effect did not persist when sleep was shifted to the daytime. The number of oscillations was similar in both experimental series and was not affected by sleep. No systematic concordance was found between glucose and insulin secretion rate oscillations and the rapid eye movement-nonrapid eye movement sleep cycles, despite them having similar periodicities. This study demonstrates that increased amplitude of glucose and insulin secretion rate oscillations is related to sleep rather than to the time of day, without any associated frequency variations.(ABSTRACT TRUNCATED AT 250 WORDS)