Spectral analysis of the heart rate variability in sleep

Spectral analysis of heart rate variability (HRV) during overnight polygraphic recording was performed in 11 healthy subjects. The total spectrum power, power of the VLF, LF and HF spectral bands and the mean R-R were evaluated. Compared to Stage 2 and Stage 4 non-REM sleep, the total spectrum power was significantly higher in REM sleep and its value gradually increased in the course of each REM cycle. The value of the VLF component (reflects slow regulatory mechanisms, e.g. the renin-angiotensin system, thermoregulation) was significantly higher in REM sleep than in Stage 2 and Stage 4 of non-REM sleep. The LF spectral component (linked to the sympathetic modulation) was significantly higher in REM sleep than in Stage 2 and Stage 4 non-REM sleep. On the contrary, a power of the HF spectral band (related to parasympathetic activity) was significantly higher in Stage 2 and Stage 4 non-REM than in REM sleep. The LF/HF ratio, which reflects the sympathovagal balance, had its maximal value during REM sleep and a minimal value in synchronous sleep. The LF/HF ratio significantly increased during 5-min segments of Stage 2 non-REM sleep immediately preceding REM sleep compared to 5-min segments of Stage 2 non-REM sleep preceding the slow-wave sleep. This expresses the sympathovagal shift to sympathetic predominance occurring before the onset of REM sleep. A significant lengthening of the R-R interval during subsequent cycles of Stage 2 non-REM sleep was documented, which is probably related to the shift of sympathovagal balance to a prevailing parasympathetic influence in the course of sleep. This finding corresponds to a trend of a gradual decrease of the LF/HF ratio in subsequent cycles of Stage 2 non-REM sleep.     

Cardiac Autonomic Activity During Human Sleep: Analysis of Sleep Stages and Sleep Cycles

In this study characteristics of cardiac functioning were investigated in nine subjects during their nocturnal sleep. The pre-ejection period and the high frequency component of heart rate variability were used as indices of cardiac sympathetic and parasympathetic activity of the autonomic nervous system respectively. Heart rate and the autonomic indices were assessed across physiological determined sleep stages and consecutive temporal sleep cycles. Repeated measures ANOVA analyses indicated a significant pattern of heart rate as a function of sleep stages, which was mirrored by parasympathetic activity. Further, a significant decrease of heart rate as a function of sleep cycles was mirrored by an increase of sympathetic activity. Moreover, non-REM/REM differences revealed a dominant role of parasympathetic activity during sleep stages as well as sleep cycles. These findings demonstrate that sympathetic activity is influenced by time asleep, whereas parasympathetic activity is influenced by the depth of sleep.     

Cardiac Autonomic Activity During Human Sleep: Analysis of Sleep Stages and Sleep Cycles

In this study characteristics of cardiac functioning were investigated in nine subjects during their nocturnal sleep. The pre-ejection period and the high frequency component of heart rate variability were used as indices of cardiac sympathetic and parasympathetic activity of the autonomic nervous system respectively. Heart rate and the autonomic indices were assessed across physiological determined sleep stages and consecutive temporal sleep cycles. Repeated measures ANOVA analyses indicated a significant pattern of heart rate as a function of sleep stages, which was mirrored by parasympathetic activity. Further, a significant decrease of heart rate as a function of sleep cycles was mirrored by an increase of sympathetic activity. Moreover, non-REM/REM differences revealed a dominant role of parasympathetic activity during sleep stages as well as sleep cycles. These findings demonstrate that sympathetic activity is influenced by time asleep, whereas parasympathetic activity is influenced by the depth of sleep.     

Decreased fractal component of human heart rate variability during non-REM sleep

The physiological significance of the fractal component of short-term, spontaneous heart rate variability (HRV) in humans remains unclear. The aim of the present study was to gain further information about the respective fractal components by extracting them from HRV, blood pressure variability (BPV), and instantaneous lung volume (ILV) time series via coarse graining spectral analysis in nine healthy subjects during waking and sleep states. The results show that the contribution made by the fractal component to the total variance in the beat-to-beat R-R interval declined significantly as the depth of non-rapid eye movement (non-REM) sleep increased, that the ILV time series was largely periodic (i.e., nonfractal), and that BPV was unaffected by sleep stage. Finally, the fractal component of HRV during REM sleep was found to be quite similar to that seen during waking. These results suggest that mechanisms involving electroencephalographic desynchronization and/or conscious states of the brain are reflected in the fractal component of HRV.     

Heart rate variability in healthy humans during night sleep

Polysomnography has been performed and heart rate variability has been studied during night sleep in healthy young subjects of both sexes. It has been shown that, on average, a shift in autonomic support towards parasympathicotonia occurs during sleep, with a maximum at stages III and IV of NREM sleep. At stage II of NREM sleep and during REM sleep, a short-term activation of the sympathetic nervous system comparable to wakefulness is observed.     

Complexity of heart rate fluctuations in near-term sheep and human fetuses during sleep.

We investigated how the complexity of fetal heart rate fluctuations (fHRF) is related to the sleep states in sheep and human fetuses. The complexity as a function of time scale for fetal heart rate data for 7 sheep and 27 human fetuses was estimated in rapid eye movement (REM) and non-REM sleep by means of permutation entropy and the associated Kullback-Leibler entropy. We found that in humans, fHRF complexity is higher in non-REM than REM sleep, whereas in sheep this relationship is reversed. To show this relation, choice of the appropriate time scale is crucial. In sheep fetuses, we found differences in the complexity of fHRF between REM and non-REM sleep only for larger time scales (above 2.5 s), whereas in human fetuses the complexity was clearly different between REM and non-REM sleep over the whole range of time scales. This may be due to inherent time scales of complexity, which reflect species-specific functions of the autonomic nervous system. Such differences have to be considered when animal data are translated to the human situation.     

Relationship between renal sympathetic nerve activity and arterial pressure during REM sleep in rats

The relationship between renal sympathetic nerve activity (RSNA) and systemic arterial pressure obtained during rapid eye movement (REM) sleep was compared with that obtained in other sleep and awake states. Electrodes for the measurements of RSNA, electrocardiogram, electromyogram, and electroencephalogram and a catheter for the measurement of systemic arterial pressure were implanted while the animals were under aseptic conditions at least 5 days before the experiment. During the transition from non-REM (NREM) to REM sleep, RSNA and heart rate (HR) decreased immediately by 46 +/- 2% (P < 0.05) and 22 +/- 3 beats/min (P < 0.05), respectively, over 3 s after the onset of REM sleep. Meanwhile, systemic arterial pressure increased gradually after the onset of REM sleep, which was apparently independent of the changes in RSNA. During REM sleep, the relationships between RSNA/HR and systemic arterial pressure were dissociated compared with that obtained during the other behavioral states. These data indicate that the interdependency between systemic arterial pressure and RSNA during REM sleep is likely to be modified compared with other behavioral states.     

Selective REM sleep deprivation during daytime. II. Muscle atonia in non-REM sleep

One of the hallmarks of rapid eye movement (REM) sleep is muscle atonia. Here we report extended epochs of muscle atonia in non-REM sleep (MAN). Their extent and time course was studied in a protocol that included a baseline night, a daytime sleep episode with or without selective REM sleep deprivation, and a recovery night. The distribution of the latency to the first occurrence of MAN was bimodal with a first mode shortly after sleep onset and a second mode 40 min later. Within a non-REM sleep episode, MAN showed a U-shaped distribution with the highest values before and after REM sleep. Whereas MAN was at a constant level over consecutive 2-h intervals of nighttime sleep, MAN showed high initial values when sleep began in the morning. Selective daytime REM sleep deprivation caused an initial enhancement of MAN during recovery sleep. It is concluded that episodes of MAN may represent an REM sleep equivalent and that it may be a marker of homeostatic and circadian REM sleep regulating processes. MAN episodes may contribute to the compensation of an REM sleep deficit.     

Cardiopulmonary regulation after rapid-eye-movement sleep deprivation.

Arterial blood pressure, chest movement, electroencephalogram, and electromyogram were monitored in six normotensive Sprague-Dawley rats for 4 h/day 3 days before and 4 days after 114 h of rapid-eye-movement (REM) sleep deprivation. During recovery sleep immediately after REM sleep deprivation (RD), there was a significant increase in the amount of time spent in REM sleep. During this rebound in REM sleep, there was a significant rise (26%) in heart rate in wakefulness, non-REM sleep, and REM sleep during the first 4 h after RD. Systolic blood pressure was also significantly elevated (14%) but only during wakefulness before recovery sleep. Rats with the greatest waking systolic blood pressure after RD had the lowest REM sleep rebound in the 4 h immediately after RD (r = -0.885, P less than 0.05). The rise in heart rate, systolic blood pressure, and REM sleep time evident on day 1 immediately after RD was absent on recovery days 2-4. The respiratory rate tended to be higher throughout the recovery period in every state of consciousness; however, these values never reached the level of significance. In the initial recovery sleep period, regulation of heart rate was more disrupted by REM sleep deprivation than either arterial blood pressure or respiratory rate.     

Light-Dark Difference in Arterial Pressure Variability During REM Sleep in the Rat

We have observed mean arterial pressure (MAP) variability during rapid eye movement (REM) sleep and brain temperature (Tb) in the rat during both light and dark periods over 24 h. MAP was measured using a telemetric device with a computer data capture and analysis system. As markers of MAP variability, the maximum and coefficient of variation (CV%) of MAP during REM sleep were determined. The following results were obtained: (a) there was a light-dark difference in MAP during non-REM (NREM) sleep and Tb during both NREM and REM sleep; (b) the increase of MAP in going from NREM to REM sleep in the light period was greater than that in the dark period, whereas the increase of Tb in the light period was not different from that in the dark period; (c) the maximum and CV% for MAP during REM sleep in the light period were greater than those in the dark period; (d) there was a negative correlation between the average Tb and MAP CV% during REM sleep. We suggest that phasic fluctuation of MAP during REM sleep may be influenced, in part, by a factor independent of sleep mechanisms.     

Light-Dark Difference in Arterial Pressure Variability During REM Sleep in the Rat

We have observed mean arterial pressure (MAP) variability during rapid eye movement (REM) sleep and brain temperature (Tb) in the rat during both light and dark periods over 24 h. MAP was measured using a telemetric device with a computer data capture and analysis system. As markers of MAP variability, the maximum and coefficient of variation (CV%) of MAP during REM sleep were determined. The following results were obtained: (a) there was a light-dark difference in MAP during non-REM (NREM) sleep and Tb during both NREM and REM sleep; (b) the increase of MAP in going from NREM to REM sleep in the light period was greater than that in the dark period, whereas the increase of Tb in the light period was not different from that in the dark period; (c) the maximum and CV% for MAP during REM sleep in the light period were greater than those in the dark period; (d) there was a negative correlation between the average Tb and MAP CV% during REM sleep. We suggest that phasic fluctuation of MAP during REM sleep may be influenced, in part, by a factor independent of sleep mechanisms.     

Increased ventricular premature contraction frequency during rem sleep in patients with coronary artery disease and obstructive sleep apnea

Background

Patients with obstructive sleep apnea are reported to have a peak of sudden cardiac death at night, in contrast to patients without apnea whose peak is in the morning. We hypothesized that ventricular premature contraction (VPC) frequency would correlate with measures of apnea and sympathetic activity.

Methods

Electrocardiograms from a sleep study of 125 patients with coronary artery disease were evaluated. Patients were categorized by apnea-hypopnea index (AHI) into Moderate (AHI <15) or Severe (AHI>15) apnea groups. Sleep stages studied were Wake, S1, S2, S34, and rapid eye movement (REM). Parameters of a potent autonomically-based risk predictor for sudden cardiac death called heart rate turbulence were calculated.

Results

There were 74 Moderate and 51 Severe obstructive sleep apnea patients. VPC frequency was affected significantly by sleep stage (Wake, S2 and REM, F=5.8, p<.005) and by AHI (F=8.7, p<.005). In Severe apnea patients, VPC frequency was higher in REM than in Wake (p=.011). In contrast, patients with Moderate apnea had fewer VPCs and exhibited no sleep stage dependence (p=.19). Oxygen desaturation duration per apnea episode correlated positively with AHI (r²=.71, p<.0001), and was longer in REM than in non-REM (p<.0001). The heart rate turbulence parameter TS correlated negatively with oxygen desaturation duration in REM (r²=.06, p=.014).

Conclusions

Higher VPC frequency coupled with higher sympathetic activity caused by longer apnea episodes in REM sleep may be one reason for increased nocturnal death in apneic patients.     

Sleep-Stage Correlates of Hippocampal Electroencephalogram in Primates

It has been demonstrated in the rodent hippocampus that rhythmic slow activity (theta) predominantly occurs during rapid eye movement (REM) sleep, while sharp waves and associated ripples occur mainly during non-REM sleep. However, evidence is lacking for correlates of sleep stages with electroencephalogram (EEG) in the hippocampus of monkeys. In the present study, we recorded hippocampal EEG from the dentate gyrus in monkeys overnight under conditions of polysomnographical monitoring. As result, the hippocampal EEG changed in a manner similar to that of the surface EEG: during wakefulness, the hippocampal EEG showed fast, desynchronized waves, which were partly replaced with slower waves of intermediate amplitudes during the shallow stages of non-REM sleep. During the deep stages of non-REM sleep, continuous, slower oscillations (0.5–8 Hz) with high amplitudes were predominant. During REM sleep, the hippocampal EEG again showed fast, desynchronized waves similar to those found during wakefulness. These results indicate that in the monkey, hippocampal rhythmic slow activity rarely occurs during REM sleep, which is in clear contrast to that of rodents. In addition, the increase in the slower oscillations of hippocampal EEG during non-REM sleep, which resembled that of the surface EEG, may at least partly reflect cortical inputs to the dentate gyrus during this behavioral state.     

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.     

Nonlinear analysis of continuous ECG during sleep II. Dynamical measures

The hypothesis that cardiac rhythms are associated with chaotic dynamics implicating a healthy flexibility has motivated the investigation of continuous ECG with methods of nonlinear system theory. Sleep is known to be associated with modulations of the sympathetic and parasympathetic control of cardiac dynamics. Thus, the differentiation of ECG signals recorded during different sleep stages can serve to determine the usefulness of nonlinear measures in discriminating ECG states in general. For this purpose the following six nonlinear measures were implemented: correlation dimension D2, Lyapunov exponent L1. Kolmogorov entropy K2, as well as three measures derived from the analysis of unstable periodic orbits. Results of this study show that continuous ECG signals can be differentiated from linear stochastic surrogates by each of the nonlinear measures. The most significant finding with respect to the sleep-related differentiation of ECG signals is an increase in dominant chaoticity assessed by L1 and a reduction in the degrees of freedom estimated by D2 during REM sleep compared to slow wave sleep. Our findings suggest that the increase in dominant chaoticity during REM sleep with regard to time-continuous nonlinear analysis is comparable to an increased heart rate variability. The reduction in the correlation dimension may be interpreted as an expression of the withdrawal of respiratory influences during REM sleep. Received: 7 June 1999 / Accepted in revised form: 10 December 1999     

Basal forebrain acetylcholine release during REM sleep is significantly greater than during waking

Cholinergic neurons of the basal forebrain supply the neocortex with ACh and play a major role in regulating behavioral arousal and cortical electroencephalographic activation. Cortical ACh release is greatest during waking and rapid eye movement (REM) sleep and reduced during non-REM (NREM) sleep. Loss of basal forebrain cholinergic neurons contributes to sleep disruption and to the cognitive deficits of many neurological disorders. ACh release within the basal forebrain previously has not been quantified during sleep. This study used in vivo microdialysis to test the hypothesis that basal forebrain ACh release varies as a function of sleep and waking. Cats were trained to sleep in a head-stable position, and dialysis samples were collected during polygraphically defined states of waking, NREM sleep, and REM sleep. Results from 22 experiments in four animals demonstrated that means +/- SE ACh release (pmol/10 min) was greatest during REM sleep (0.77 +/- 0.07), intermediate during waking (0.58 +/- 0.03), and lowest during NREM sleep (0.34 +/- 0.01). The finding that, during REM sleep, basal forebrain ACh release is significantly elevated over waking levels suggests a differential role for basal forebrain ACh during REM sleep and waking.     

Identification of development and autonomic nerve activity from heart rate variability in preterm infants

Heartbeat intervals, which are determined basically by regular excitations of the sinoatrial node, show significant fluctuation referred to as the heart rate variability (HRV). The HRV is mostly due to nerve activities through the sympathetic and parasympathetic branches of the autonomic nervous system (ANS). In recent years, it has been recognized that the HRV shows a greater complexity than ever expected, suggesting that it includes much information about ANS activities. In this study, we investigated relationship between HRV and development in preterm infants. To this end, heartbeat intervals were continuously recorded from 11 preterm infants in NICU. The recording periods were ranging from several days to weeks depending on the individuals. The HRV at various ages was then characterized by several indices. They include power spectrum as well as the mean and standard deviation of the series. For the power spectrum, the low-frequency band power (LF), high-frequency band power (HF), LF/HF (the ratio between LF and HF), beta (scaling exponent of the spectrum) were estimated. The detrended fluctuation analysis (DFA) was also employed to obtain short- and long-range scaling exponents. Each of these indices showed a correlation with the age. We showed that the long-range scaling exponent, derived from the DFA, was most significantly correlated with the age, suggesting that it could be a robust index to characterize the development of preterm infants.     

Distinct narcolepsy syndromes in Orexin receptor-2 and Orexin null mice: molecular genetic dissection of Non-REM and REM sleep regulatory processes

Narcolepsy-cataplexy, a neurological disorder associated with the absence of hypothalamic orexin (hypocretin) neuropeptides, consists of two underlying problems: inability to maintain wakefulness and intrusion of rapid eye movement (REM) sleep into wakefulness. Here we document, using behavioral, electrophysiological, and pharmacological criteria, two distinct classes of behavioral arrests exhibited by mice deficient in orexin-mediated signaling. Both OX2R(-/-) and orexin(-/-) mice are similarly affected with behaviorally abnormal attacks of non-REM sleep ("sleep attacks") and show similar degrees of disrupted wakefulness. In contrast, OX2R(-/-) mice are only mildly affected with cataplexy-like attacks of REM sleep, whereas orexin(-/-) mice are severely affected. Absence of OX2Rs eliminates orexin-evoked excitation of histaminergic neurons in the hypothalamus, which gate non-REM sleep onset. While normal regulation of wake/non-REM sleep transitions depends critically upon OX2R activation, the profound dysregulation of REM sleep control unique to the narcolepsy-cataplexy syndrome emerges from loss of signaling through both OX2R-dependent and OX2R-independent pathways.     

Quantitative differences among EMG activities of muscles innervated by subpopulations of hypoglossal and upper spinal motoneurons during non-REM sleep - REM sleep transitions: a window on neural processes in the sleeping brain

In the rat, a species widely used to study the neural mechanisms of sleep and motor control, lingual electromyographic activity (EMG) is minimal during non-rapid eye movement (non-REM) sleep and then phasic twitches gradually increase after the onset of REM sleep. To better characterize the central neural processes underlying this pattern, we quantified EMG of muscles innervated by distinct subpopulations of hypoglossal motoneurons and nuchal (N) EMG during transitions from non-REM sleep to REM sleep. In 8 chronically instrumented rats, we recorded cortical EEG, EMG at sites near the base of the tongue where genioglossal and intrinsic muscle fibers predominate (GG-I), EMG of the geniohyoid (GH) muscle, and N EMG. Sleep-wake states were identified and EMGs quantified relative to their mean levels in wakefulness in successive 10 s epochs. During non-REM sleep, the average EMG levels differed among the three muscles, with the order being N>GH>GG-I. During REM sleep, due to different magnitudes of phasic twitches, the order was reversed to GG-I>GH>N. GG-I and GH exhibited a gradual increase of twitching that peaked at 70-120 s after the onset of REM sleep and then declined if the REM sleep episode lasted longer. We propose that a common phasic excitatory generator impinges on motoneuron pools that innervate different muscles, but twitching magnitudes are different due to different levels of tonic motoneuronal hyperpolarization. We also propose that REM sleep episodes of average durations are terminated by intense activity of the central generator of phasic events, whereas long REM sleep episodes end as a result of a gradual waning of the tonic disfacilitatory and inhibitory processes.     

Effect of sleep stage on breathing in children with central hypoventilation.

The early literature suggests that hypoventilation in infants with congenital central hypoventilation syndrome (CHS) is less severe during rapid eye movement (REM) than during non-REM (NREM) sleep. However, this supposition has not been rigorously tested, and subjects older than infancy have not been studied. Given the differences in anatomy, physiology, and REM sleep distribution between infants and older children, and the reduced number of limb movements during REM sleep, we hypothesized that older subjects with CHS would have more severe hypoventilation during REM than NREM sleep. Nine subjects with CHS, aged (mean +/- SD) 13 +/- 7 yr, were studied. Spontaneous ventilation was evaluated by briefly disconnecting the ventilator under controlled circumstances. Arousal was common, occurring in 46% of REM vs. 38% of NREM trials [not significant (NS)]. Central apnea occurred during 31% of REM and 54% of NREM trials (NS). Although minute ventilation declined precipitously during both REM and NREM trials, hypoventilation was less severe during REM (drop in minute ventilation of 65 +/- 23%) than NREM (drop of 87 +/- 16%, P = 0.036). Despite large changes in gas exchange during trials, there was no significant change in heart rate during either REM or NREM sleep. We conclude that older patients with CHS frequently have arousal and central apnea, in addition to hypoventilation, when breathing spontaneously during sleep. The hypoventilation in CHS is more severe during NREM than REM sleep. We speculate that this may be due to increased excitatory inputs to the respiratory system during REM sleep.