Lacunar stroke and heart rate variability during sleep

ObjectiveAutonomic instability during sleep can influence the risk of cerebrovascular diseases. In this study, we performed a polygraphy to evaluate, heart rate variability (HRV) in a group of patients with lacunar stroke that is a condition at high risk of recurrence.MethodsTwenty-one lacunar stroke patients were enrolled one month after stroke occurrence. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). The presence of common sleep disorders and autonomic changes during the night was investigated by a polygraphy monitoring. Results were compared with those obtained in a group of 21 healthy subjects.ResultsPatients and controls were similar for age, sex distribution and main cardiovascular risk factors with the exception of the body mass index. Significant differences were detected for all polysomnographic (PSG) parameters and for the PSQI score. By considering HRV values, patients with pathologic values (12 patients, HRV>2) showed significantly higher values in BMI (31 ± 2.9 vs. 26.6 ± 3.6, p = 0.006) and PSQI scores (7.9 ± 2.6 vs. 4.2 ± 1.9) with respect to patients with normal HRV values (nine patients, HRV≤2).ConclusionsThe results of this study suggest that the prevalence of nocturnal autonomic dysfunction is high in lacunar stroke patients even in the absence of the commonest sleep-related disorders. An abnormal HRV may contribute to increase the risk of stroke recurrence. Based on our results, the indication to polygraphy in patients with lacunar stroke should be carefully considered.     

Effects of bright light exposure on heart rate variability during sleep in young women.

To investigate the effects of evening bright light on the autonomic nervous system, heart rate variability (HRV) during sleep was analyzed in dim light (DL) and bright light (BL) conditions. We recorded polysomnography in nine healthy young women aged 20-21 years. Time series of % delta power was calculated in the 0.49-2.20 Hz band. Heart rate variability was analyzed from a 10-min segment of slow wave sleep. The low- to high-frequency ratio and the low-frequency component decreased significantly in the BL conditions compared with the DL conditions. However, the power of the high-frequency component did not change in the two conditions. These results indicate that evening BL affects the autonomic nervous system during slow wave sleep.     

Correlation between electroencephalography and heart rate variability during sleep

It is known that autonomic nervous activities change in correspondence with sleep stages. However, the characteristics of continuous fluctuations in nocturnal autonomic nerve tone have not been clarified in detail. The study aimed to determine the possible correlation between the electroencephalogram (EEG) and autonomic nervous activities, and to clarify in detail the nocturnal fluctuations in autonomic nerve activities. Overnight EEGs and electrocardiograms of seven healthy males were obtained. These EEGs were analyzed by fast Fourier transformation algorithm to extract delta, sigma and beta power. Heart rate and heart rate variability (HRV) were calculated in consecutive 5-min epochs. The HRV indices of low frequency (LF), high frequency (HF) and LF/HF ratio were calculated from the spectral analysis of R-R intervals. The sleep stages were manually scored according to Rechtschaffen and Kales' criteria. Low frequency and LF/HF were significantly lower during non-rapid eye movement (NREM) than REM, and were lower in stages 3 and 4 than in stages 1 and 2. Furthermore, delta EEG showed inverse correlations with LF (r = - 0.44, P < 0.001) and LF/HF (r = - 0.41, P < 0.001). In contrast, HF differed neither between REM and NREM nor among NREM sleep stages. Detailed analysis revealed that correlation was evident from the first to third NREM, but not in the fourth and fifth NREM. Delta EEG power showed negative correlations with LF and LF/HF, suggesting that sympathetic nervous activities continuously fluctuate in accordance with sleep deepening and lightening.     

Effects of caffeine on heart rate and QT variability during sleep

Administration of caffeine in the evening produces poor sleep. Patients with insomnia have characteristic electrocardiogram (ECG) changes, including increased heart rate (HR), increased sympathetic activity, and decreased parasympathetic activity. Fifteen young adult normal subjects slept in the laboratory for several nights prior to randomization into a caffeine protocol where subjects received caffeine 400 mg 30 min prior to one night of sleep and placebo randomly prior to another night. ECG was sampled at a rate of 500 Hz and recorded onto a PC. Data samples of 256-s periods of the ECG trace were taken from wake (before sleep), stage II, and REM for placebo and caffeine conditions. A peak detection algorithm was used to identify the R-R intervals (in milliseconds) from the ECG. A common QT variability algorithm was used to find the QT interval for each beat using the time-stretch model. The powers for HR and QT series were integrated in the bands of LF (low frequency: 0.04-0.15 Hz) and HF (high frequency: 0.15-0.5 Hz) bands. There was a significant caffeine by sleep stage interaction for LF/HF ratios (F = 4.0; df = 2, 18; P = .04). LF/HF ratios were significantly higher during REM following caffeine administration. There was also a significant caffeine by sleep stage interaction for QTvi (QT variability normalized for mean QT interval divided by HR variability normalized for mean HR; F = 5.6; df = 2, 12; P = .02). QTvi was also significantly higher during REM following caffeine administration. The higher LF/HF ratios and QTvi during REM are most likely due to the sympathetic effects of caffeine. These findings suggest that excessive caffeine intake may result in adverse cardiovascular events in vulnerable subjects.     

High-frequency heart rate variability during worry predicts stress-related increases in sleep disturbances

ObjectiveThe aim of this study was to evaluate whether high-frequency heart rate variability (HF-HRV) during waking restfulness and during worry predicts increases in sleep disturbances in response to a stressful life event.MethodsA longitudinal study following up 22 individuals from well-defined periods of lower and higher stress was conducted. HF-HRV during waking restfulness and in response to a worry induction was measured during a low-stress period. Sleep disturbances were assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Insomnia Severity Index (ISI) during low-stress and high-stress periods.ResultsDuring both the low- and high-stress periods, lower HF-HRV during worry was associated with greater PSQI scores. Importantly, lower HF-HRV during the worry induction prospectively predicted greater increases in the PSQI score from the low-stress to the high-stress periods.ConclusionHF-HRV during worry might represent an index of vulnerability to stress-induced sleep disturbances.     

Human heart rate variability and sleep stages

With the aim of better understanding the dynamic changes in sympatho-vagal tone occurring during the night, human heart rate variability (HRV) during the various sleep stages was evaluated by means of autoregressive spectral analysis.Each recording consisted of an electroencephalogram, an electrooculogram, and electromyogram, an electrocardiogram, and a spirometry trace. All of the data were sampled and stored in digital form.Sleep was analysed visually, but HRV was analysed off-line by means of original software using Burg's algorithm to calculate the LF/HF ratio (LF: 0.04–0.12 Hz; HF: 0.15–0.35 Hz) for each sleep stage.Seven healthy subjects (four males; mean age 35 years) were enrolled in the study.Our findings show a progressive and significant reduction in the LF/HF ratio through sleep stages S1–S4, as a result of an increase in the HF component; this indicates the prevalence of parasympathetic activity during slow-wave sleep. During wakefulness, S1 and REM, the LF/HF values were similar and close to 1.

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Sommario Allo scopo di comprendere meglio le modificazioni del tono del sistema nervoso autonomo durante la notte, è stata valutata la variabilità del ritmo cardiaco (HRV) negli stadi del sonno, impiegando una metodica autoregressiva di analisi spettrale.Ciascuna registrazione consisteva di elettroencefalogramma, elettro-oculogramma, elettromiografia, spirometria ed elettrocardiogramma, campionati e registrati in forma digitale.L'ipnogramma è stato ottenuto ispettivamente, mentre l'analisi dell'HRV è stata eseguita con un software dedicato, utilizzando l'algoritmo di Burg e calcolando il rapporto LF/HF (LF: 0.04–0.12 Hz; HF: 0.15–0.35 Hz) per ciascuno stadio del sonno.Sono stati arruolati nello studio 7 soggetti sani (4 maschi, età media 35 anni). I nostri risultati mostrano una progressiva e significativa diminuzione di LF/HF dallo stadio 1 al 4, imputabile ad un aumento del tono del parasimpatico (aumento della componente HF), mentre il valore del rapporto durante veglia, REM e fase 1 è risultato simile (circa 1).

     

Postnatal development of rat pups is altered by prenatal methamphetamine exposure

There are studies showing that drug abuse during pregnancy may have impairing effect on progeny of drug-abusing mothers. Methamphetamine (MA) is one of the most common illicit drugs throughout the world. The purpose of the present study was to assess the effect of prenatal MA exposure on postnatal development of rat pups before the time of separation from their mothers. Female rats were injected with MA (5 mg/kg daily) for the duration of their pregnancy. Pups were then tested throughout the lactation period. They were weighed daily and the ano-genital distance was measured on postnatal day (PD) 1. Development of postural motor reaction was tested by righting reflex on surface between PD 1 and 12, and righting reflex in mid-air after PD 12 until successfully accomplished. On PD 15 homing test was examined as a test of pup acute learning. On PD 23 sensory-motor coordination was examined using the rotarod and bar-holding tests. Additionally, the markers of physical maturation, such as eye opening, testes descent in males and vaginal opening in females were also recorded. The birth weight in prenatally MA-exposed pups was lower than in controls or saline-exposed pups regardless of sex. There were no changes induced by prenatal MA exposure in weight gain or in sexual maturation. In righting reflexes, we demonstrated that pups exposed prenatally to MA were slower in righting reflex on surface and that they accomplished the test of righting reflex in mid-air later than controls or saline-exposed pups. The performance of homing test was not affected by prenatal drug exposure. The sensory-motor coordination was impaired in prenatally MA-exposed pups when testing in the rotarod test. Also, the number of falls in the bar-holding test was higher in MA-exposed pups than in controls. There were no sex differences in any measures. Thus, the present study demonstrated that prenatal MA exposure impairs development of postural motor movements of rat pups during the first 3 weeks after birth, while not affecting physical or sexual maturation.     

Nocturnal magnetic field exposure: gender-specific effects on heart rate variability and sleep.

OBJECTIVE: To determine if controlled exposure to power-frequency magnetic fields alters heart rate variability (HRV) and polysomnographic endpoints in healthy men (n=22) and women (n=24), 40-60 years of age. METHODS: A randomized, double-blind, crossover design was used. Study endpoints collected during all-night exposure to 60 Hz magnetic fields at an occupational intensity (resultant flux density=28.3 microTesla, microT) were compared to similar endpoints obtained under equivalent, counterbalanced, no-exposure (< or =0.2 microT) control conditions. RESULTS: Older men, but not women, exposed to the magnetic fields showed power reductions in the LF band of the HRV frequency spectrum, which is associated with sympathetically-mediated blood pressure and thermoregulatory control (P<0.04). Older women, but not men, exposed to the fields showed a pattern of disrupted sleep, with reductions in the duration of REM sleep (P=0.03), and strong trends for reductions in sleep efficiency (P=0.06) and total sleep time (P=0.06). CONCLUSIONS: The gender-specific effects seen here with older volunteers replicate the results of previous exposure studies with younger men and women.     

Spectral analyses of electroencephalography and heart rate variability during sleep in normal subjects

We investigated the relationship between electroencephalogram (EEG) activity and autonomic nervous system function using spectral analyses of EEG and heart rate variability (HRV) in healthy subjects during sleep. Eleven subjects were enrolled in this study. From EEG, the spectral edge frequencies (SEFs including SEF50, SEF90 and SEF95) were calculated. From electrocardiogram (ECG), the spectral powers of low-frequency band (LF: 0.04-0.15 Hz), high-frequency band (HF: 0.15-0.4 Hz) and the ratio of LF to HF (LF/HF) were calculated. During sleep, each set of data was obtained as the average of a 5-min measurement. We found that SEFs and LF/HF or LF decreased simultaneously and periodically, suggesting simultaneous depression of EEG activity and relative sympathetic activity, and SEFs significantly correlated with LF/HF and LF in all subjects during sleep, but not with HF. The existence of a clear correlation of SEFs with LF or LF/HF may offer a simple approach to estimate the relationship between EEG activity and autonomic nervous system function during sleep.     

Accelerated neuromuscular development in the rat with prenatal exposure to nicotine

Nicotine, administered to pregnant Sprague-Dawley rats either throughout gestation or during two selective prenatal periods before or after muscular innervation (i.e. before or after gestational day 13), accelerated the maturation of developing nerve and muscle as viewed in 2-week-old offspring. Prenatal treatment of rats with nicotine (tartrate salt; 0.25 mg/kg twice a day; i.p.) induced marked changes in the contractile force and speed of the developing extensor digitorum longus (EDL) muscle when tested in situ on 14 to 15-day-old pups. In all nicotine treatment groups isometric twitch and tetanus half contraction durations were shorter than controls. Use of 2,3,5-triphenyltetrazolium chloride, a biochemical indicator for cellular respiration, showed that totigestational nicotine administration increases cellular metabolic activity of EDL muscle. Hypertrophy of adrenal glands in these animals also was noted. While each of the three courses of nicotine administration accelerated muscle development and maturation, nicotine during the first half of prenatal development, prior to EDL muscle innervation, produced a more dramatic effect than nicotine during the second half of prenatal life.     

Developmental changes in heart rate variability during exposure to prolonged hypercapnia in piglets

The hypothesis that hypercapnia-induced differences in heart rate variability (HRV) would emerge during early maturation was tested using a developing porcine model. Piglets were randomly assigned to either exposed (10% CO2 for 1 h) or control (100% O2) conditions, and then to one of three study groups: (a) 5-8 days old, (b) 13-15 days old, (c) 26-34 days old. Experiments were performed on pairs of age-and litter-matched animals that were anesthetized, paralyzed, and artificially ventilated. HRV was evaluated using power spectral analysis, SD of differences between successive RR intervals, and cardiac interval analysis. Statistical comparisons of simultaneously studied animals were made at baseline, 15 and 55 min after onset of hypercapnia, and 2 h after offset of hypercapnia. Our analyses revealed that only HRV of 26-34-day-old animals differed significantly from values of control animals. Cardiac intervals of those animals were distributed in such a manner that hypercapnia likely elicited coactivation of sympathetic and parasympathetic systems. Comparison of the distribution of cardiac intervals for other animals showed that 5-8-day-old animals had high frequency of balanced intervals at baseline that remained so during hypercapnia. Given that such coactivation may be neuroprotective, the paucity of balanced intervals in 13-15-day-old animals could mean that the end of the second postnatal week is associated with increased vulnerability.     

State-related differences in heart rate variability in bipolar disorder

Heart rate variability (HRV) is a validated measure of sympato-vagal balance in the autonomic nervous system. HRV appears decreased in patients with bipolar disorder (BD) compared with healthy individuals, but the extent of state-related alterations has been sparingly investigated. The present study examined differences in HRV between affective states in BD.A heart rate and movement sensor weighing 8 g collected average acceleration, heart rate and the two slowest and fastest heart beats (of the most recent 16 beats) every 30 s over a period of at least three consecutive weekdays and nights in a prospective longitudinal design from a total of 31 different affective states in 16 outpatients with BD. A proxy measure of HRV was calculated as the difference between the second-shortest and the second-longest inter-beat-interval collected during each of the epochs. Analyses were based on over 100.000 HRV data-points.In unadjusted analyses and in analyses adjusted for age, gender and heart rate, during a manic state HRV was increased by 18% compared with a depressed state (e^B = 1.18, 95% CI: 1.16–1.20, p < 0.001) and increased by 17% compared with a euthymic state (e^B = 1.17, 95% CI: 1.15–1.19, p < 0.001), whereas there was no difference between a depressive state and a euthymic state (e^B = 0.98, 95% CI: 0.96–1.00, p = 0.12). Further inclusion of BMI as a covariate did not alter any of the associations.HRV appears to be altered in a state-dependent manner in bipolar disorder and could represent a candidate state marker. Further studies with larger sample sizes are warranted.     

Abnormal heart rate variability in a subject with second degree atrioventricular blocks during sleep.

OBJECTIVE: We compare the profiles of heart rate variability (HRV) during sleep stages in 9 healthy controls and one subject with second degree atrioventricular blocks (AVB), investigating the role of sympathovagal balance in such pathology. METHOD: Sleep and cardiac records were taken for one night in 9 male subjects from 21:00 to 07:00 h and for two nights in a male subject with AVB. Time and frequency domain indexes of HRV were calculated over 5 min-periods. RESULTS: In one subject without any daytime heart disease, 253 and 318 AVB of type 2 (Mobitz 2) were observed during the two experimental nights, predominantly during rapid eye movement (REM) sleep and the surrounding sleep stage 2 in the second half of the night. In the 9 control subjects, absolute HRV indexes and low frequency (LF)/(LF+high frequency, HF) (where LF and HF are low frequency and high frequency power) were low during slow wave sleep, and significantly increased during REM sleep and the preceding sleep stage 2. In the subject with AVB, these HRV indexes were abnormally low during all sleep stages, with a predominant increase in parasympathetic activity as inferred from low LF/(LF+HF). During wake, however, LF/(LF+HF) normally increased, and the tachycardia observed with the arousal that terminates SWS was preserved in the subject with AVB. CONCLUSION: These results suggest that in the subject with second degree atrioventricular blocks, sleep processes, particularly during REM sleep, create a specific neurological background that prevents an increase in sympathetic tone and triggers cardiac pauses.     

The impact of cyclic alternating pattern on heart rate variability during sleep in healthy young adults

Objective: Cyclic alternating pattern (CAP) consists of arousal-related phasic events while the complementary condition, non-CAP (NCAP), is characterized by a rhythmic background activity, reflecting a condition of stable arousal, during non-REM sleep. The arousal swings that accompany the appearance of CAP on the EEG are associated with transient variations of muscle tone and autonomic activities, including heart rate (HR). The aim of our study was to evaluate HR variability in relation to CAP during non-REM sleep in healthy adults.Methods: Ten healthy subjects (mean age=28.1 years) underwent 8 h polysomnography. HR variations were measured by power spectrum analysis. The ECG signals were segmented in correspondence of the different sleep stages and different CAP conditions.Results: A significant difference between CAP and NCAP conditions was found in low frequency (LF) component (increased in CAP) and high frequency (HF) component (decreased in CAP). LF/HF ratio was increased in CAP.Conclusion: Physiological fluctuations of the EEG arousal level influence cardiac autonomic activity in normal subjects. The studies on nocturnal variation in sympathetic and vagal tone should take in account the microstructural sleep changes, other than the conventional polysomnographic parameters.     

Inverse coupling between ultradian oscillations in delta wave activity and heart rate variability during sleep.

OBJECTIVE: We investigate the relationship between changes in heart rate variability and electroencephalographic (EEG) activity during sleep. METHOD: Nine male subjects with regular non-rapid-eye movement-rapid-eye movement (NREM-REM) sleep cycles were included in the study. They underwent EEG and cardiac recordings during one experimental night. Heart rate variability was determined over 5-min periods by the ratio of low frequency to low frequency plus high frequency power [LF/(LF+HF)] calculated using spectral analysis of R-R intervals. EEG spectra were analyzed using a fast Fourier transform algorithm. RESULTS: We found an ultradian 80-120 min rhythm in the LF/(LF+HF) ratio, with high levels during rapid eye movement (REM) sleep and low levels during slow wave sleep (SWS). During sleep stage 2 there was a progressive decrease in the transition from REM sleep to SWS, and an abrupt increase from SWS to REM sleep. These oscillations were significantly coupled in a 'mirror-image' to the overnight oscillations in delta wave activity, which reflect sleep deepening and lightening. Cardiac changes preceded EEG changes by about 5 min. CONCLUSIONS: These findings demonstrate the existence of an inverse coupling between oscillations in delta wave activity and heart rate variability. They indicate a non-uniformity in sleep stage 2 that underlies ultradian sleep regulation.     

Relationship between frequency spectrum of heart rate variability and autonomic nervous activities during sleep in newborns

Introduction

We analyzed the frequency spectrum of two neonatal sleep stages, namely active sleep and quiet sleep, and the relationship between these sleep stages and autonomic nervous activity in 74 newborns and 16 adults as a comparison.

Obstructive sleep apnea and heart rate asymmetry microstructure during sleep

Purpose

Heart rate decelerations and accelerations have unequal input to heart rate variability (HRV) and patterns created by consecutive cardiac cycles—this phenomenon is known as heart rate asymmetry (HRA). The analysis of monotonic runs of heart rate decelerations and accelerations provides a detailed insight into the HRA microstructure and thus of HRV.

Aim

To evaluate the relation between the severity of obstructive sleep apnea (OSA) and the HRA microstructure during sleep.

Methods

Seventy-eight patients with suspected OSA underwent overnight polysomnography. The 300-min ECGs from the polysomnography were selected and analyzed. The HRA microstructure was quantified by measuring (1) the contribution of monotonic runs of decelerations or accelerations of different lengths to the number of all sinus beats, and (2) the length of the longest deceleration and acceleration runs.

Results

There were 19 patients with no/mild OSA (Apnea/Hypopnea Index (AHI) 5.1 ± 2.5/h), 18 with moderate OSA (AHI 21.8 ± 4.0/h) and 41 with severe OSA (AHI 42.8 ± 17.4/h). Patients with severe OSA had significantly reduced deceleration and acceleration runs of length 1 compared to the moderate OSA group, and compared to patients with no/mild OSA they had an increased number of longer runs (from 5 to 10 for accelerations and from 5 to 8 for decelerations; p < 0.05 for all comparisons). The longest acceleration runs were significantly longer in severe OSA group (p < 0.05) than in subjects with no/mild OSA.

Conclusions

HRA microstructure is related with OSA severity. An increased number of longer deceleration and acceleration runs is more common in severe OSA patients.     

Sex differences in neurotensin and substance P following nicotine self‐administration in rats

Investigator‐administered nicotine alters neurotensin and substance P levels in Sprague‐Dawley rats. This finding suggested a role of the dopamine‐related endogenous neuropeptides in nicotine addiction. We sought to extend this observation by determining the responses of neurotensin and substance P systems (assessed using radioimmunoassay) in male and female rats following nicotine self‐administration (SA). Male and female Sprague‐Dawley were trained to self‐administer nicotine, or receive saline infusions yoked to a nicotine‐administering rat during daily sessions (1‐h; 21 days). Brains were extracted 3 h after the last SA session. Nicotine SA increased tissue levels of neurotensin in the males in the anterior and posterior caudate, globus pallidus, frontal cortex, nucleus accumbens core and shell, and ventral tegmental area. Nicotine SA also increased tissue levels of neurotensin in the females in the anterior caudate, globus pallidus, nucleus accumbens core and shell, but not in the posterior caudate, frontal cortex, or ventral tegmental area. There were fewer sex differences observed in the substance P systems. Nicotine SA increased tissue levels of substance P in both the males and females in the posterior caudate, globus pallidus, frontal cortex, nucleus accumbens shell, and ventral tegmental area. A sex difference was observed in the nucleus accumbens core, where nicotine SA increased tissue levels of substance P in the males, yet decreased levels in the females. The regulation of neuropeptides following nicotine SA may play a role in the susceptibility to nicotine dependence in females and males. Synapse 70:336–346, 2016 . © 2016 Wiley Periodicals, Inc.