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Peripheral vasoconstriction during REM sleep detected by a new plethysmographic method

  • Technion - Israel Institute of Technology, Haifa, Israel


Rapid-eye-movement (REM) sleep is associated with more sympathetic activation than is NONREM sleep1, 2. So far, there are no data regarding vascular tone during REM and NONREM sleep in humans. Using a new plethysmographic technique to measure peripheral arterial tone (PAT), we report here that REM sleep in humans is associated with considerable peripheral vasoconstriction. The apparatus is essentially a plethysmograph that, unlike models now available, is able to envelop the finger up to and beyond its tip with a uniform pressure field. The applied pressure field is sufficient to substantially unload arterial wall tension, thereby improving the dynamic range of the system, while preventing the potential occurrence of venous engorgement that promotes vasoconstriction. Pressure within the probe originates from a pressurized balloon located over its outside wall. Pulsatile volume signals were recorded as optical density changes from the finger's palmar surface within the applied pressure field. The device was tolerated well for extended periods.
To the editor—Rapid-eye-movement (REM)
sleep is associated with more sympathetic
activation than is NONREM sleep1,2. So
far, there are no data regarding vascular
tone during REM and NONREM sleep in
humans. Using a new plethysmographic
technique to measure peripheral arterial
tone (PAT), we report here that REM sleep
in humans is associated with consider-
able peripheral vasoconstriction. The ap-
paratus is essentially a plethysmograph
that, unlike models now available, is able
to envelop the finger up to and beyond
its tip with a uniform pressure field. The
applied pressure field is sufficient to sub-
stantially unload arterial wall tension,
thereby improving the dynamic range of
the system, while preventing the poten-
tial occurrence of venous engorgement
that promotes vasoconstriction. Pressure
within the probe originates from a pres-
surized balloon located over its outside
wall. Pulsatile volume signals were
recorded as optical density changes from
the finger’s palmar surface within the ap-
plied pressure field. The device was toler-
ated well for extended periods.
We measured pulsatile finger blood
flow throughout the night in 9 normal
young adults (25–40 years of age) and 17
patients with light-to-moderate sleep
apnea syndrome (35–60 years of age;
mean respiratory disturbance index, less
than 30). The PAT signals were analyzed
by a dedicated computer program in
terms of mean relative peak to peak am-
plitude in 1-minute ‘bins’ for the first
and second REM periods, and for 20 min-
utes of NONREM periods before and after
each REM period. PAT amplitudes were
expressed as percentages of the mean am-
plitude during the initial 5 minutes of
the NONREM period preceding each
REM period. Minutes with body move-
ments were omitted before analysis. In
both groups, REM sleep was associated
with considerable attenuation of the PAT
signal (Fig. 1). The decrease in amplitude
began during NONREM sleep and
reached a nadir during REM sleep. As
there were neither differences between
groups nor differences between the first
and second REM periods, we pooled data
and analyzed these by repeated measures
ANOVA . The percent change during
REM sleep (–16.3 ± 19.7%) was signifi-
cantly higher than that during NONREM
sleep before (–3.39 ± 14%) or after (–2.39
± 27.2%) REM sleep (P < 0.009). The
curves describing the change in ampli-
tudes during the transition from NON-
REM to REM and back to NONREM sleep
could be fitted with a quadratic trend (P <
0.02) with a minimum occurring 8.5
minutes after the start of REM sleep.
The intense sympathetic activation
during REM sleep and the preponderance
of REM in the early morning hours have
led to the suggestion that REM sleep may
be responsible for increased cardiac
events seen at this time3. Although we
have no data to show that REM-related
vasoconstriction also occurs in larger
blood vessels or is specific to the periph-
ery, the report that in a canine model, ex-
perimental occlusion of the coronary
arteries during REM sleep results in a
greater than expected decrease in coro-
nary blood flow4indicates that REM-re-
lated vasoconstriction may predispose
patients with compromised coronary ar-
teries to ischemic events during sleep5.
1Sleep Laboratory,
B. Rappaport Faculty of Medicine,
Technion-Israel Institute of Technology,
Haifa, Israel
2Itamar Medical Ltd.,
Caesarea, Israel
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Peripheral vasoconstriction during REM sleep detected by a
new plethysmographic method
Fig. 1 Peripheral vasoconstruction during REM sleep. a, Compressed
records of the PAT signal and electro-oculogram (EOG) during the transition
from NONREM to REM and back to NONREM sleep, in two subjects. The
EOG records help identify the times of the traditionally scored REM periods.
The gradual decrease in PAT amplitude starts at least 30 min before the be-
ginning of the traditionally scored REM sleep. *, Body movements artifact.
b, Mean percent change (± s.e.m.) in PAT amplitude, referenced to the
mean amplitude in the initial 5 minutes of the preceding NONREM period,
averaged across all 54 REM periods. The curve describing the
NONREM–REM transition is synchronized to the first minute of REM sleep
(vertical line). The curve for succeeding NONREM periods is synchronized
to the first NONREM minute (vertical line). As REM periods varied in length,
the percent change during REM sleep were calculated only when there were
at least five data points. Red line, quadratic trend fitted to the data.
© 2000 Nature America Inc. •
© 2000 Nature America Inc. •
... Besides PRV, the ANS may modulate peripheral BF differently during different sleep stages. For example, the peripheral arterial tone (PAT) signal from BF, an index of sympathetic vasoconstrictor mechanisms (Pépin et al., 2009;Lanfranchi and Somers, 2010), decreases from Wk to NREM sleep and reaches its nadir during REM sleep (Lavie et al., 2000). The decreasing pattern of the PAT Table S6). ...
... Furthermore, previous studies have shown that the modulation of BF by sleep stages (e.g., REM sleep with higher sympathetic activity) may be different between the peripheral and cerebral regions. While peripheral BF may decrease in REM sleep compared with NREM sleep (Lavie et al., 2000), cerebral BF shows a marked increase instead (Hanak and Somers, 2011;Klingelhófer, 2012). Therefore, peripheral BF has its own characteristics during sleep, and these characteristics may be different across sleep stages. ...
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Pulse rate variability (PRV), derived from Laser Doppler flowmetry (LDF) or photoplethysmography, has recently become widely used for sleep state assessment, although it cannot identify all the sleep stages. Peripheral blood flow (BF), also estimated by LDF, may be modulated by sleep stages; however, few studies have explored its potential for assessing sleep state. Thus, we aimed to investigate whether peripheral BF could provide information about sleep stages, and thus improve sleep state assessment. We performed electrocardiography and simultaneously recorded BF signals by LDF from the right-index finger and ear concha of 45 healthy participants (13 women; mean age, 22.5 ± 3.4 years) during one night of polysomnographic recording. Time- and frequency-domain parameters of peripheral BF, and time-domain, frequency-domain, and non-linear indices of PRV and heart rate variability (HRV) were calculated. Finger-BF parameters in the time and frequency domains provided information about different sleep stages, some of which (such as the difference between N1 and rapid eye movement sleep) were not revealed by finger-PRV. In addition, finger-PRV patterns and HRV patterns were similar for most parameters. Further, both finger- and ear-BF results showed 0.2–0.3 Hz oscillations that varied with sleep stages, with a significant increase in N3, suggesting a modulation of respiration within this frequency band. These results showed that peripheral BF could provide information for different sleep stages, some of which was complementary to the information provided by PRV. Furthermore, the combination of peripheral BF and PRV may be more advantageous than HRV alone in assessing sleep states and related autonomic nervous activity.
... It can be considered as a gauge of the tone of the sympathetic nervous system (Shelley, 2007). It is activation leads to higher vasoconstriction (Lavie et al., 2000;Iani et al., 2004) and hence to lower values of BVPA or BVP (Nestoriuc and Martin, 2007). Thanks to the parasympathetic nervous system of vasodilatation (e.g., respiratory sinus arrhythmia and baroreflex, see Vila et al., 2007), the BVPA values on the other hand grow (Lin et al., 2015) or exhibit a flatter curve (Kumazawa et al., 1964). ...
... We presume that compared with listening to forest sounds (pleasant natural acoustic stimuli), listening to the sound of a chainsaw, which can be classified in the category of unpleasant, monotonous and urban acoustic stimuli, will be associated more with the physiological manifestations of defensive arousal (Vila et al., 2007). Specifically, we presume that due to stronger contraction of muscle fibres, higher defensive arousal (sustained sympathetic arousal) will cause greater vasoconstriction that will manifest primarily in lower BVPA values (Lavie et al., 2000;Martin et al., 2007). While listening to both sounds, a similar increase can be expected in HR values (Ulrich et al., 1991;Parrot et al., 1992) or a decrease of SCL values (Gomez and Danuser, 2004;Medvedev et al., 2015) and R values, but RR values in particular will occur (Boiten, 1998;Gomez and Danuser, 2004). ...
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We explored differences in the course of physiological functions and in the subjective evaluations in response to listening to a 7-min recording of the sound of a chainsaw and to the sounds of a forest. A Biofeedback 2000x-pert apparatus was used for continual recording of the following physiological functions in 50 examined persons: abdominal and thoracic respiration and their amplitude and frequency, electrodermal activity (skin conductance level), finger skin temperature, heart rate (pulse, blood volume pulse and blood volume pulse amplitude) and heart rate variability (HRV). The group of 25 subjects listening to the sound of a chainsaw exhibited significantly lower values of blood volume pulse amplitude, lower values in peak alpha frequency HRV and higher values in peak high-frequency HRV. In the time interval from 80 s to 209 s, in which the two groups showed the greatest differences, lower values of blood volume pulse were also recorded while listening to the sound of a chainsaw. Listening to the sound of a chainsaw is associated with a greater feeling of fatigue and higher tension, while listening to the sounds of a forest is even considered to elicit feelings of improved learning abilities. The assumption that listening to the sound of a chainsaw results in higher defense arousal was confirmed. The greater variability which is exhibited by a majority of physiological functions while listening to the forest sounds may also be an innovative finding. It seems that there are two types of arousal (sympathetic and parasympathetic) following from correlations between physiological functions and subjective assessment. Low values of blood volume pulse amplitude are especially important from the health perspective. They correspond to the amount of vasoconstriction which occurs in the endothelial dysfunction related to increased mortality, incidence of myocardial infarction, leg atherosclerosis and topically to COVID-19.
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In most cultures the age-old saying, health is wealth has been widely used in some form or other. Healthy living is desirable by all. A variety of definitions have been offered from time to time to explain healthy living under various circumstances. The World Health Organization has defined health as “a state of complete physical, mental and social well-being and not merely the absence of disease and infirmity”. The normal physical and mental states of an individual are dependent on an equilibrium of functioning of various systems of the body. The healthy body is one entity, which suffers due to dysfunction of one or more of the systems in the body. Supported by evidence, we argue that loss of a fundamental and an instinct behaviour, sleep and REMS in particular, of an individual modulates the level of noradrenaline (NA) and that affects almost all physiological processes. Thus, maintenance of optimum sleep is necessary for a healthy living. We argue that ageing is a natural progression of living. However, through life as one may experience sleep loss to various degrees and that may affect one or more physiological processes, ageing persons may experience symptoms depending on the system(s) gets affected. Thus, we propose that as ageing cannot be avoided, maintenance of optimum sleep may favour healthy ageing or ageing with minimum pathophysiological changes. Accordingly, we also recommend regular and routine sleep recording so that any significant variation may act as an early indication of future disease(s).
... It can be detected by identifying specific "sympathetic signatures" in the PAT signal, such as reported by . These authors reported that in addition to the phasic changes in PAT signal amplitude characteristic of arousals, a different facet of the PAT signal during sleep was that REM stage sleep is characterized by tonic reductions in PAT amplitude of extended duration [44]. ...
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Sleep-disordered breathing (SDB) is a common comorbidity in patients with heart failure (HF). Prevalence of the most common subtypes of SDB, central sleep apnea (CSA) and obstructive sleep apnea (OSA), is increasing, which is concerning due to the association of SDB with increased mortality in patients with heart failure. Despite an increasing burden of CSA in HF, it is difficult to detect using current diagnostic tools and the treatment modalities are limited by variable efficacy and patient adherence. Though positive airway pressure therapies remain the cornerstone of OSA treatment, the management of CSA in the setting of HF continues to evolve. The association of the presence of CSA with worse prognosis in HF patients warrants the need for routine screening for signs and symptoms of CSA in this population. In this review, we examine the connection between CSA and HF, highlighting advancements in timely diagnostics, treatment modalities, and strategies to promote facilitation of compliance in this high-risk cohort.
The day-night differences in environmental light intensity and ambient temperature play significant roles in modulating the sleep and wakefulness of humans. This chapter summarizes existing knowledge regarding the mechanisms through which ambient light and temperature affect sleep; (2) reviews the current evidence regarding the relationship between these environmental factors and the sleep of children and adolescents; and (3) integrates and appraise the results of the empirical studies and identify future research directions based on gaps in our current understanding. It is expected that integrated current knowledge regarding the impact of ambient light and temperature on sleep will facilitate the creation of high-quality sleep environments that can promote healthy sleep among children and adolescents.
New trends in sleep medicine make use of the increased computational power of digital transformation. A current trend toward fewer sensors on the body of the sleeper and to more data processing from derived signals is observed. Telemedicine technologies are used for data transmission and for better patient management in terms of diagnosis and in terms of treatment of chronic conditions.
Assessing sleep in children is challenging. While polysomnography (PSG) remains the gold standard test in laboratory, many times it has been difficult to perform polysomnography in small children. They tend to remove the electrodes and thus the failure rate of PSG in children is relatively high. Furthermore, in pediatric obstructive sleep apnea (OSA), sometimes the single laboratory finding is hypercapnia, and hence measuring CO2 is also required, which may even increase the failure rate. In addition, PSG (regardless of CO2) is relatively complex and is disadvantageous when children need several consecutive nights of assessments. Some newer technologies such as pulse transit time, sophisticated computerized analyses of ECG, or peripheral arterial tonometry are validated when assessing sleep in adults and are in various stages of development/research for usage in children (in the home environment). Other technologies such as actigraphy are excellent for children, including longitudinal assessment of nights-weeks, but the data provided are limited compared to PSG. Some even newer technologies such as snoring sound analyzers, wearable activity trackers, or even smartphone applications may open the horizon for simpler sleep assessments in children at home, although the science and data in this regard are still insufficient. This chapter deals with various technologies, reports their advantages and disadvantages, and attempts to foresee the future for sleep assessment in children.
The present study investigated autonomic activity during NREM and REM sleep stages and wakefulness by spectral analysis of heart rate variability. The results demonstrated that NREM sleep in humans was characterized by a widely different autonomic activation pattern than REM sleep: high parasympathetic activity was found in NREM, while REM was characterized by attenuated vagal tone, and augmented sympathetic activity. The overall pattern during wakefulness showed an intermediate position between NREM and REM patterns; parasympathetic activity was lower than in NREM and higher than in REM, with an opposite trend for sympathetic activity.
The events that convert chronic coronary artery disease to acute myocardial infarction or sudden cardiac death are poorly understood. We studied the time of day of onset of nonfatal myocardial infarction (as judged objectively by CK-MB values, n = 703) and sudden cardiac death (as judged by death certificates, n = 2,203) to determine if there was an increased incidence associated with a particular time of day. Both conditions were found to have prominent circadian rhythms with a primary peak in the morning and a secondary peak in the evening. Platelet aggregability, which has been proposed as a component of myocardial infarction and sudden cardiac death, was also found to increase during the morning. These findings suggest a mechanism for myocardial infarction and sudden cardiac death and may lead to improved methods of prevention.
The sleep-wake cycle results in distinctive patterns of autonomic nervous system activity. The present study examined the effects of rapid eye movement and slow-wave sleep on coronary hemodynamic function in chronically instrumented dogs. Mean arterial blood pressure was measured via a catheter in the aorta, and coronary blood flow was determined with Doppler probes placed around the left circumflex and right coronary artery. Identification of sleep stages was accomplished by means of electrodes implanted via the frontal sinus to record electro-oculogram, electromyogram, and electroencephalogram. Results indicated that during slow-wave sleep there were moderate but significant reductions in heart rate, 9% decreases in left coronary blood flow, and increases in coronary vascular resistance. In rapid-eye-movement sleep, the circumflex coronary blood flow base line returned to awake levels, and there were pronounced, phasic 35% increases in heart rate and 35% increases in coronary blood flow lasting 15-20 s. These surges were eliminated by stellectomy, indicating that they were mediated by the sympathetic nervous system.
We have demonstrated in a previous study that in the normal heart REM sleep induces surges in heart rate and coronary blood flow which are abolished by bilateral stellectomy. To study the effects of sleep in the stenosed coronary circulation, dogs were instrumented with Doppler flow probes and hydraulic occluders around the left circumflex coronary artery to measure coronary blood flow and to produce a 60% flow reduction. Catheters were placed in the aorta to measure mean arterial blood pressure. Electrodes were implanted via the frontal sinus to identify sleep stages. In the absence of stenosis, mean blood pressure was 95 +/- 3 mmHg, HR was 111 +/- 4 bpm, and coronary blood flow was 33 +/- 2 ml/min. During stenosis, REM induced episodic increases in heart rate which were accompanied by 38% decreases in coronary blood flow. We conclude that in the stenosed coronary circulation, REM sleep produces episodic sinus tachycardia and coronary blood flow reduction.
The early hours of the morning after awakening are associated with an increased frequency of events such as myocardial infarction and ischemic stroke. The triggering mechanisms for these events are not clear. We investigated whether autonomic changes occurring during sleep, particularly rapid-eye-movement (REM) sleep, contribute to the initiation of such events. We measured blood pressure, heart rate, and sympathetic-nerve activity (using microneurography, which provides direct measurements of efferent sympathetic-nerve activity related to muscle blood vessels) in eight normal subjects while they were awake and while in the five stages of sleep. The mean (+/- SE) amplitude of bursts of sympathetic-nerve activity and levels of blood pressure and heart rate declined significantly (P < 0.001), from 100 +/- 9 percent, 90 +/- 4 mm Hg, and 64 +/- 2 beats per minute, respectively, during wakefulness to 41 +/- 9 percent, 80 +/- 4 mm Hg, and 59 +/- 2 beats per minute, respectively, during stage 4 of non-REM sleep. Arousal stimuli during stage 2 sleep elicited high-amplitude deflections on the electroencephalogram (called K complexes), which were frequently associated with bursts of sympathetic-nerve activity and transient increases in blood pressure. During REM sleep, sympathetic-nerve activity increased significantly (to 215 +/- 11 percent; P < 0.001) and the blood pressure and heart rate returned to levels similar to those during wakefulness. Momentary restorations of muscle tone during REM sleep (REM twitches) were associated with cessation of sympathetic-nerve discharge and surges in blood pressure. REM sleep is associated with profound sympathetic activation in normal subjects, possibly linked to changes in muscle tone. The hemodynamic and sympathetic changes during REM sleep could play a part in triggering ischemic events in patients with vascular disease.
Patients with coronary heart disease (CHD) and obstructive sleep apnea may have an increased cardiac risk due to nocturnal myocardial ischemia triggered by apnea-associated oxygen desaturation. Sleep structure in patients with obstructive sleep apnea is fragmented by activation of the central nervous system (CNS) (arousal) due to obstructive apneas. Nocturnal myocardial ischemia may lead to activation of the CNS as well. Fourteen patients with obstructive sleep apnea and CHD disease and seven patients suffering from obstructive sleep apnea without CHD were studied. Overnight sleep studies and simultaneous six-lead ECG recordings were performed. In addition, sleep studies and ECG recordings were performed with administration of a sustained-release nitrate in these patients in a double-blinded crossover design. Analysis of three nights' recordings revealed 144 episodes of nocturnal myocardial ischemia in six subjects. Five patients had underlying CHD and one patient exhibited diffuse wall defects of the coronary arteries; also, 85.4% of ischemic episodes were concomitant with apneas and oxygen desaturation > 3%, and 77.8% of ischemic episodes occurred during rapid eye movement (REM) sleep, although total amount of REM sleep was only 18% of total sleep time. Mean oxygen saturation was significantly lower (p < 0.05) during apnea-associated ischemic episodes than during nonapnea-associated ischemia (77.3% vs 93.1%). Nitrate administration did not reduce ischemic episodes. Sleep architecture (macrostructure) exhibited a reduction in sleep stages non-REM 3 and 4 and REM sleep. Comparing the microstructure of sleep (arousals) within episodes with and without ischemia but similar criteria like sleep stage, apnea activity, and oxygen saturation, we found significantly more (p < 0.01) and severe (p < 0.001) arousals during periods with myocardial ischemia than during control episodes. In addition, microstructure of sleep was disturbed by myocardial ischemia itself in absence of apneas. It is concluded that patients with CHD and obstructive sleep apnea are endangered by apnea-associated ischemia and that these ischemic episodes lead to activation of the CNS and additional fragmentation of sleep. Patients with nocturnal ischemia should be screened for underlying sleep apnea even if nitrate therapy fails.