Enhanced conductive body heat loss during sleep increases slow-wave sleep and calms the heart.

Substantial evidence suggests that the circadian decline of core body temperature (CBT) triggers the initiation of human sleep, with CBT continuing to decrease during sleep. Although the connection between habitual sleep and CBT patterns is established, the impact of external body cooling on sleep remains poorly understood. The main aim of the present study is to show whether a decline in body temperatures during sleep can be related to an increase in slow wave sleep (N3). This three-center study on 72 individuals of varying age, sex, and BMI used an identical type of a high-heat capacity mattress as a reproducible, non-disturbing way of body cooling, accompanied by measurements of CBT and proximal back skin temperatures, heart rate and sleep (polysomnography). The main findings were an increase in nocturnal sleep stage N3 (7.5 ± 21.6 min/7.5 h, mean ± SD; p = 0.0038) and a decrease in heart rate (- 2.36 ± 1.08 bpm, mean ± SD; p < 0.0001); sleep stage REM did not change (p = 0.3564). Subjects with a greater degree of body cooling exhibited a significant increase in nocturnal N3 and a decrease in REM sleep, mainly in the second part of the night. In addition, these subjects showed a phase advance in the NREM-REM sleep cycle distribution of N3 and REM. Both effects were significantly associated with increased conductive inner heat transfer, indicated by an increased CBT- proximal back skin temperature -gradient, rather than with changes in CBT itself. Our findings reveal a previously far disregarded mechanism in sleep research that has potential therapeutic implications: Conductive body cooling during sleep is a reliable method for promoting N3 and reducing heart rate.

Effects of manipulating body temperature on sleep in postmenopausal women.

STUDY OBJECTIVES: A decline in sleep quality, slow wave sleep (SWS) and slow wave activity (SWA) are common in older adults. Prior studies have shown that manipulating body temperature during sleep can increase SWS/SWA. The aim of this study was to determine the effects of manipulation of body temperatures during sleep, using a high heat capacity mattress, on SWS/SWA and heart rate in post-menopausal women. METHODS: Twenty-four healthy postmenopausal women between 40 and 75 years of age (mean age 62.4 ± 8.2 years, mean BMI 25.4 ± 3.5 kg/m2) were randomized in a single-blind, counterbalanced, cross-over manner to sleep on either a high heat capacity mattress (HHCM) or a low heat capacity mattress (LHCM) a week apart. Sleep was recorded using polysomnography during an 8-h sleep opportunity. Core and peripheral temperature were recorded using an ingestible capsule and thermochron respectively. RESULTS: In comparison to the LHCM, sleep on HHCM exhibited a selective increase in SWS (average increase in Stage N3 of 9.6 min (2.1%), p = 0.04) and in slow oscillatory (SO) activity (0.5-1 Hz) in the first NREM/REM cycle (p = 0.04). In addition, the HHCM induced a greater reduction in core body temperature (p = 0.002). The reduction in core body temperature (first 180 min after lights out) from LHCM to HHCM was associated (r = 0.5, p = 0.012) with the increase in SO activity (SO cycle 1 and 2/cycle 3 and 4). Average heart rate was 1.6 beats/minute lower across the night on the HHCM compared to the LHCM (p = 0.001). CONCLUSIONS: The results of this study indicate that manipulation of body temperature during sleep may be a useful approach to enhance SWS sleep in postmenopausal women.

Thermal discomfort with cold extremities in relation to age, gender, and body mass index in a random sample of a Swiss urban population.

BACKGROUND: The aim of this epidemiological study was to investigate the relationship of thermal discomfort with cold extremities (TDCE) to age, gender, and body mass index (BMI) in a Swiss urban population. METHODS: In a random population sample of Basel city, 2,800 subjects aged 20-40 years were asked to complete a questionnaire evaluating the extent of cold extremities. Values of cold extremities were based on questionnaire-derived scores. The correlation of age, gender, and BMI to TDCE was analyzed using multiple regression analysis. RESULTS: A total of 1,001 women (72.3% response rate) and 809 men (60% response rate) returned a completed questionnaire. Statistical analyses revealed the following findings: Younger subjects suffered more intensely from cold extremities than the elderly, and women suffered more than men (particularly younger women). Slimmer subjects suffered significantly more often from cold extremities than subjects with higher BMIs. CONCLUSIONS: Thermal discomfort with cold extremities (a relevant symptom of primary vascular dysregulation) occurs at highest intensity in younger, slimmer women and at lowest intensity in elderly, stouter men.

Effects of sleep on a high-heat capacity mattress on sleep stages, EEG power spectra, cardiac interbeat intervals and body temperatures in healthy middle-aged men‡.

STUDY OBJECTIVES: This study deals with the question whether a slow (non-disturbing) reduction of core body temperature (CBT) during sleep increases sleep stage N3 and EEG slow wave energy (SWE) and leads to a slowing of heart rate in humans. PARTICIPANTS: Thirty-two healthy male subjects with a mean ± SD age 46 ± 4 years and body mass index 25.2 ± 1.8 kg/m2. METHODS: A high-heat capacity mattress (HM) was used to lower body temperatures in sleep and was compared to a conventional low-heat capacity mattress (LM) in a double-blinded fashion. Polysomnography was performed accompanied by measurements of skin-, core body- and mattress surface-temperatures, and heart rate. EEG power spectral analyses were carried out using Fast Fourier Transform. Interbeat intervals were derived from the electrocardiogram. RESULTS: The HM led to a larger decline in CBT, mediated through higher heat conduction from the core via the proximal back skin onto the mattress together with reduced heart rate. These effects occurred together with a significant increase in sleep stage N3 and standardized slow wave energy (sSWE, 0.791-4.297 Hz) accumulated in NREM sleep. In the 2nd half of the night sSWE increase was significantly correlated with body temperature changes, for example with CBT decline in the same phase. CONCLUSIONS: A HM subtly decreases CBT, leading to an increased amount of sleep stage N3 and of sSWE, as well as a slowing of heart rate.

Melatonin reduces arousal and startle responsiveness without influencing startle habituation or affective startle modulation in young women.

Melatonin has been suggested to affect human emotion, but conflicting evidence exists. Therefore, we tested the effect of a single dose of a 4 mg prolonged release formulation of melatonin on a biologically based model of emotional processing. Affective modulation of acoustic white noise startle (103 dB) by emotional slides selected from the International Affective Picture System (IAPS) was assessed in 16 healthy young women twice, in a double-blind, placebo-controlled, balanced cross-over design. Melatonin significantly reduced startle responsiveness, but did not impact affective startle modulation, nor startle habituation. Melatonin significantly reduced arousal ratings and induced a parasympathetically dominated heart rate variability pattern indicative of a non-aroused state. We conclude that melatonin reduces arousal and startle responsiveness. However, no evidence for a direct emotion-modulating effect of melatonin was found in this healthy cohort.

Cold extremities and difficulties initiating sleep: evidence of co-morbidity from a random sample of a Swiss urban population.

Difficulties initiating sleep (DIS) can frequently occur in psychiatric disorders but also in the general population. The primary vasospastic syndrome is a functional disorder of vascular regulation in otherwise healthy subjects complaining of thermal discomfort from cold extremities (TDCE). Laboratory studies have shown a close relationship between long sleep onset latency and increased distal vasoconstriction in healthy young subjects. Considering these findings, the aims of the Basel Survey were to assess the prevalence rates for DIS and TDCE and to determine whether both symptoms can be associated in the general population. In a random population sample of Basel-Stadt, 2800 subjects (age: 20-40 years) were requested to complete a questionnaire on sleep behavior and TDCE (response rate: 72.3% in women, n = 1001; 60.0% in men, n = 809). Values of DIS and TDCE were based on questionnaire-derived scores. In addition, TDCE was externally validated in a separate group of subjects (n = 256) by finger skin temperature measurements--high TDCE values were significantly associated with low finger skin temperature. A total of 31.1% of women and 6.9% of men complain of TDCE. In contrast, prevalence rates of DIS were only slightly higher in women in comparison to men (9.3% versus 6.7%, P < 0.1). Irrespective of gender, each seventh subject complaining of TDCE had concomitant DIS and the relative risk in these subjects was approximately doubled. Therefore, a thermophysiological approach to DIS may be relevant for its differential diagnosis and its treatment.

Influence of timed nutrient diet on depression and light sensitivity in seasonal affective disorder.

Seasonal Affective Disorder (SAD) patients crave and eat more carbohydrates (CHO) in fall-winter when depressed, especially in the evenings, and feel energetic thereafter. Evening CHO-rich meals can phase delay circadian rhythms, and glucose increases retinal response to light. We studied timed CHO- or protein-rich (PROT) diet as a putative therapy for SAD. Unmedicated, DSM-IV-diagnosed depressed women with SAD (n=22, 19-63 yrs) in the follicular phase of the menstrual cycle (present in 19) were randomized to nine days of eating approximately 1600 kcal of either CHO before 12:00 h (n=9), CHO after 18:00 h (n=6), or PROT after 18:00 h (n=7); only water was allowed for the rest of the day. Measurements included the depression questionnaire SIGH-SAD (with 21-item Hamilton depression subscale), Eating Behavior Questionnaire (DEBQ), percentage fat (by bioimpedancemetry), clinical biochemistry (glucose, cholesterol, triglycerides, TSH, T4, cortisol), and electroretinogram (ERG). No differential effects of diet were found on any of the studied parameters (except DEBQ). Clinically, participants improved slightly; the 21-HDRS score (mean+/-SD) decreased from 19.6+/-6.4 to 14.4+/-7.4 (p=.004). Percent change correlated significantly with menstrual day at diet onset (mood improved the first week after menstruation onset), change in available sunshine (more sunlight, better mood), and initial percentage fat (fatter patients improved more). Scotopic ERG amplitude was diminished after treatment (p=.025, three groups combined), probably due to greater exposure to sunshine in 14/22 subjects (partial correlation analysis significant). Keeping in mind the limitations of this ambulatory study (i.e., inability to control outdoor light exposure, small number of participants, and briefness of intervention), it is suggested that the 25% clinical improvement (of the order of magnitude of placebo) is not related to nutrient diet or its timing, but rather to natural changes during the menstrual cycle, available sunshine, and ease of dieting for fatter patients.

Sleep on a high heat capacity mattress increases conductive body heat loss and slow wave sleep.

Environmental temperature can strongly affect sleep. The habitual sleep phase is usually located between evening decline and morning rise of the circadian rhythm of core body temperature (CBT). However, the thermophysiological mechanisms promoting or disturbing sleep are not yet fully understood. The purpose of this study was to examine the effects of a high heat capacity mattress (HHCM) on CBT, skin temperatures and sleep in comparison to a conventional low heat capacity mattress (LHCM). Based on the higher heat capacity of HHCM an increase in conductive body heat loss enhances the nocturnal decline in CBT can be expected. Based on previous findings this may then be accompanied by an increase in slow wave sleep (SWS). The mattresses were studied in a randomized single-blind crossover design in fifteen healthy young men (Age: 26.9±2.1yr, BMI: 22.2±0.4kg/m2) by overnight in laboratory standard video-polysomnography in a temperature stabilized setting. CBT, room temperature, and skin and mattress surface temperatures were continuously recorded in order to get information about inner and outer body heat flow. Additionally, subjective sleep quality was estimated by visual analogue scale. In comparison to LHCM sleep on HHCM exhibited a selective increase in SWS (16%, p<0.05), increased subjective sleep quality and sleep stability [reduced cyclic alternating pattern (CAP) rate; 5.3%, p<0.01]. Additionally, analyses of the sleep stages showed in the second part of the night a significant increase in SWS and a decrease in REMS. In addition, HHCM induced a greater reduction in CBT (maximally by -0.28°C), reduced the increase in proximal skin temperatures on the back (PROBA; maximally by -0.98°C), and delayed the increase in mattress surface temperature (maximal difference LHCM-HHCM: 6.12°C). Thus, the CBT reduction can be explained by an increase in conductive heat loss to the mattress via proximal back skin regions. Regression analysis identified PROBA as the critical variable to predict inner conductive heat transfer from core to shell and SWS. In conclusion, the study expands the previous findings that a steeper nocturnal decline in CBT increases SWS and subjective sleep quality, whereas inner conductive heat transfer could be identified as the crucial thermophysiological variable, and not CBT.

The thermophysiological cascade leading to sleep initiation in relation to phase of entrainment.

This article reviews circadian thermoregulation in relation to sleep induction and phase of entrainment in the light of the comprehensive thermophysiological and chronobiological concepts of Jürgen Aschoff. The idea that temperature and sleep are interrelated is based on evolutionary history. Mammalian sleep developed in association with endothermy, and all species, independent of temporal niche, usually sleep during the circadian trough of their core body temperature (CBT) rhythm. The circadian pattern of CBT results from the balance between heat production and heat loss, the latter being relevant for sleep induction. Sleep under entrained conditions is typically initiated on the declining portion of the CBT curve when its rate of change and body heat loss is maximal. Body heat loss before lights off, via selective vasodilatation of distal skin regions, promotes sleepiness and the rapid onset of sleep. This thermophysiological effect represents the cement between the circadian clock and the sleep-wake cycle, and in turn determines phase of entrainment (Psi) and sleep onset latency (SOL). These interrelationships have been recently studied in a particular subset of the general population, mainly women, who suffer from cold hands and feet (the so-called vasospastic syndrome, VS). Women with VS exhibit not only a lower capacity to lose heat during the daytime but also a prolonged SOL, a disturbed Psi of the circadian clock with respect to the sleep-wake cycle and psychologically, a disposition to turn experienced anger inwards. This naturalistic model leads us to a more general conclusion that regulation of distal skin blood flow may have clinical relevance for insomnia, in particular sleep onset insomnia.

The human sleep-wake cycle reconsidered from a thermoregulatory point of view.

Sleep is typically initiated on the declining portion of the circadian rhythm of core body temperature (CBT) when its rate of change, and body heat loss, is maximal. Distal vasodilatation plays a primary role in the circadian regulation of body heat loss and is strongly associated with sleepiness and sleep induction. In contrast, sleep (i.e. non-REM sleep and slow-wave activity, SWA) has no or only a minor thermoregulatory function. Two lines of evidence support this statement. First, detailed analyses of thermoregulatory changes before and after lights off show clearly that they start before stage 2 sleep begins. Second, accumulation of sleep pressure with increasing time awake, increases subjective sleepiness and SWA during the succeeding recovery night, but does not influence the thermoregulatory system. Taken together, the circadian modulation of sleepiness and sleep induction is clearly associated with thermoregulatory changes, but the thermoregulatory system seems to be independent of the sleepiness/sleep regulatory system. A simplified model is presented which attempts to explain the relationship between these two systems. It is based on the main hypothesis that all thermoregulatory effects which lead to an increase in the core/shell ratio (e.g. a reduced shell by increased distal skin temperature) lead to increased sleepiness and, as a consequence, to increased sleep propensity. However, the sleepiness/sleep regulatory system feeds back onto the thermoregulatory system only indirectly via sleep-related behaviors (e.g. relaxation, lying down).

Thermoregulatory effects of melatonin in relation to sleepiness.

Thermoregulatory processes have long been implicated in the initiation of human sleep. In this paper, we review our own studies conducted over the last decade showing a crucial role for melatonin as a mediator between the thermoregulatory and arousal system in humans. Distal heat loss, via increased skin temperature, seems to be intimately coupled with increased sleepiness and sleep induction. Exogenous melatonin administration during the day when melatonin is essentially absent mimics the endogenous thermophysiological processes occurring in the evening and induces sleepiness. Using a cold thermic challenge test, it was shown that melatonin-induced sleepiness occurs in parallel with reduction in the thermoregulatory set-point (threshold); thus, melatonin may act as a circadian modulator of the thermoregulatory set-point. In addition, an orthostatic challenge can partially block the melatonin-induced effects, suggesting an important role of the sympathetic nervous system as a link between the thermoregulatory and arousal systems. A topographical analysis of finger skin temperature with infrared thermometry revealed that the most distal parts of the fingers, i.e., fingertips, represent the important skin regions for heat loss regulation, most probably via opening the arteriovenous anastomoses, and this is clearly potentiated by melatonin. Taken together, melatonin is involved in the fine-tuning of vascular tone in selective vascular beds, as circulating melatonin levels rise and fall throughout the night. Besides the role of melatonin as "nature's soporific", it can also serve as nature's nocturnal vascular modulator.

High sensitivity of human melatonin, alertness, thermoregulation, and heart rate to short wavelength light.

Light can elicit acute physiological and alerting responses in humans, the magnitude of which depends on the timing, intensity, and duration of light exposure. Here, we report that the alerting response of light as well as its effects on thermoregulation and heart rate are also wavelength dependent. Exposure to 2 h of monochromatic light at 460 nm in the late evening induced a significantly greater melatonin suppression than occurred with 550-nm monochromatic light, concomitant with a significantly greater alerting response and increased core body temperature and heart rate ( approximately 2.8 x 10(13) photons/cm(2)/sec for each light treatment). Light diminished the distal-proximal skin temperature gradient, a measure of the degree of vasoconstriction, independent of wavelength. Nonclassical ocular photoreceptors with peak sensitivity around 460 nm have been found to regulate circadian rhythm function as measured by melatonin suppression and phase shifting. Our findings-that the sensitivity of the human alerting response to light and its thermoregulatory sequelae are blue-shifted relative to the three-cone visual photopic system-indicate an additional role for these novel photoreceptors in modifying human alertness, thermophysiology, and heart rate.

Age-related attenuation of the evening circadian arousal signal in humans.

The human circadian pacemaker maintains timing and consolidation of sleep-wake behavior by opposing the build-up of homeostatic sleep pressure during the wake episode, particularly in the evening during the 'wake maintenance zone'. We tested whether age-related changes in sleep are a consequence of a weaker circadian arousal signal in the evening. Circadian rhythms and spectral components of the sleep EEG were investigated in 17 young (20-31 year) and 15 older (57-74 year) volunteers under constant posture conditions during a 40-h nap protocol (75/150 min sleep/wake schedule). Quantitative evidence for a weaker circadian arousal signal in aging arose from significantly more sleep occurring during the wake maintenance zone and higher subjective sleepiness ratings in the late afternoon and evening in the older group. In addition, we found a diminished melatonin secretion and a reduced circadian modulation of REM sleep together with less pronounced day-night differences in the lower alpha and spindle range of sleep EEG activity in the older group. Thus, our data indicate that age-related changes in sleep propensity are clearly related to a reduced circadian signal opposing the homeostatic drive for sleep.

Alteration of internal circadian phase relationships after morning versus evening carbohydrate-rich meals in humans.

The effects of a single morning and evening carbohydrate-rich meal for 3 consecutive days on circadian phase of core body temperature (CBT), heart rate, and salivary melatonin rhythms were compared under controlled constant routine conditions. In 10 healthy young men entrained to a natural light-dark cycle with regular sleep timing, CBT and heart rate were significantly elevated for approximately 8 h after the last evening carbohydrate-rich meal (EM), and nocturnal melatonin secretion (as measured by salivary melatonin and urinary 6-sulphatoxymelatonin levels) was reduced, compared to the morning carbohydrate-rich meal (MM) condition. Thus, circadian phase could not be measured until the following day due to this acute masking effect. The day after the last meal intervention, MM showed a significant advanced circadian phase position in CBT (+59+/-12 min) and heart rate (+43+/-18 min) compared to EM. However, dim-light melatonin onset was not significantly changed (+15+/-13 min). The results are discussed with respect to central (light-entrainable) and peripheral (food-entrainable) oscillators. Food may be a zeitgeber in humans for the food-entrainable peripheral oscillators, but melatonin data do not support such a conclusion for the light-entrainable oscillator in the suprachiasmatic nucleus.

Daytime variation in ambient temperature affects skin temperatures and blood pressure: Ambulatory winter/summer comparison in healthy young women.

It is widely accepted that cold exposure increases peripheral vascular resistance and arterial blood pressure (BP) and, hence, increases cardiovascular risk primarily in the elderly. However, there is a lack of concomitantly longitudinal recordings at personal level of environmental temperature (PET) and cardiophysiological variables together with skin temperatures (STs, the "interface-variable" between the body core and ambient temperature). To investigate the intra-individual temporal relationships between PET, STs and BP 60 healthy young women (52 completed the entire study) were prospectively studied in a winter/summer design for 26 h under real life conditions. The main hypothesis was tested whether distal ST (Tdist)mediates the effect of PET-changes on mean arterial BP (MAP). Diurnal profiles of cardiophysiological variables (including BP), STs and PET were ambulatory recorded. Daytime variations between 0930 and 2030 h were analyzed in detail by intra-individual longitudinal path analysis. Additionally, time segments before, during and after outdoor exposure were separately analyzed. In both seasons short-term variations in PET were positively associated with short-term changes in Tdist (not proximal ST, Tprox) and negatively with those in MAP. However, long-term seasonal differences in daytime mean levels were observed in STs but not in BP leading to non-significant inter-individual correlation between STs and BP. Additionally, higher individual body mass index (BMI) was significantly associated with lower daytime mean levels of Tprox and higher MAP suggesting Tprox as potential mediator variable for the association of BMI with MAP. In healthy young women the thermoregulatory and BP-regulatory systems are closely linked with respect to short-term, but not long-term changes in PET. One hypothetical explanation could serve recent findings that thermogenesis in brown adipose tissue is activated in a cool environment, which could be responsible for the counter-regulation of cold induced increase of BP in winter leading to no seasonal differences in MAP. Our findings suggest that the assessment of diurnal patterns of STs and PET, in addition to the conventional ambulatory BP monitoring, might improve individual cardiovascular risk prediction.

Distribution of melatonin MT1 receptor immunoreactivity in human retina.

Melatonin is synthesized in the pineal gland and retina during the night. Retinal melatonin is believed to be involved in local cellular modulation and in regulation of light-induced entrainment of circadian rhythms. The present study provides the first immunohistochemical evidence for the localization of melatonin 1a-receptor (MT1) in human retina of aged subjects. Ganglion, amacrine, and photoreceptor cells expressed MT1. In addition, MT1 immunoreactivity was localized to cell processes in the inner plexiform layer and to central vessels of the retina, as well as to retinal vessels but not to ciliary or choroidal vessels. These results support a variety of cellular and vascular effects of melatonin in the human retina. Preliminary evidence from patients with Alzheimer's disease (AD) revealed increased MT1 immunoreactivity in ganglion and amacrine cells, as well as in vessels. In AD cases photoreceptor cells were degenerated and showed low MT1 expression.

Dawn-dusk simulation light therapy of disturbed circadian rest-activity cycles in demented elderly.

We investigated whether low intensity dawn-dusk simulation (DDS), a 'naturalistic' form of light therapy designed to embed sleep in its accustomed phase, could improve the disturbed circadian rest-activity cycle, nocturnal sleep and and/or cognitive functions in dementia. A protocol of 3 weeks each of baseline, treatment and follow-up was completed by 13 patients (85yr old+/-5yr, MMSE 14+/-5; n=9 DDS versus n=4 'placebo' dim red light) who wore an activity/lux monitor throughout. There were no significant changes in clinical or cognitive status, nor modification of circadian stability or amplitude characteristics of the rest-activity cycle. However, two aspects of sleep responded to DDS but not to dim red light. The main sleep episode was 1:14h earlier during treatment (p=0.03) compared with before and after DDS. With respect to actimetry-determined sleep variables, the DDS group tended to have shortened 'sleep latency', longer 'sleep duration', more nocturnal immobility and less nocturnal activity than the dim red group (p<0.1). In parallel, nighttime light exposure tended to be reduced (p=0.07). These promising findings-after only 3 weeks of light treatment in elderly patients with advanced dementia-suggest that the circadian timing system remains functionally responsive even to low intensity DDS light. Increasing zeitgeber strength is an important strategy for improving sleep quality and timing in dementia, and DDS light therapy may provide one of the appropriate means to do so.

Circadian modulation of sequence learning under high and low sleep pressure conditions.

Humans are able to learn complex sequences even without conscious awareness. We have studied the repercussions of circadian phase and sleep pressure on the ability to learn structured sequences using a serial reaction time task (SRT). Sixteen young healthy volunteers were studied in a 40-h "constant posture protocol" under high sleep pressure (i.e. sleep deprivation) and low sleep pressure conditions (i.e. sleep satiation attained by multiple naps). Here we show that learning of different sequence structures improved after multiple naps, in particular after naps that followed the circadian peak of rapid-eye-movement (REM) sleep. This situation following sleep contrasted with the lack of learning without sleep. We have evidenced that the observed amelioration of learning new sequences came about by memorizing short sub-fragments ("chunks") of the sequence train. However, SRT performance did not deteriorate under high sleep pressure, despite the high level of sleepiness. Our data indicate that sequence learning is modulated by circadian phase, and the neurophysiological medium required for this type of learning is related to sleep.

Circadian and wake-dependent modulation of fastest and slowest reaction times during the psychomotor vigilance task.

Performance on the psychomotor vigilance task (PVT) sensitively reflects a circadian modulation of neurobehavioral functions, as well as the effect of sleep pressure developing with duration of time awake, without being confounded by a learning curve. Sixteen healthy volunteers underwent two 40-h constant posture protocols in a balanced crossover design. During these protocols, either low sleep pressure conditions were attained by an alternating cycle of 150 min of wakefulness and 75 min of sleep (NAP) protocol, or high sleep pressure conditions were achieved by total sleep deprivation (SD) protocol. During scheduled wakefulness in both protocols, the PVT was carried out every 225 min. Quantitative analysis of the lapses, slowest (90th percentile) and fastest (10th percentile) reaction times (RTs) during the protocols, indicated that the lapses and slowest RTs were sensitive to changes in homeostatic sleep pressure. Our data indicate that the difference between the fastest and slowest RTs (interpercentile range 10th-90th percentile) was particular sensitive to detect very early effects of growing sleep pressure. On the other hand, decrements in PVT performance which were related to circadian phase did not depend significantly on any categorization (such as percentiles of the RTs).

Effect of melatonin on vascular responses of porcine ciliary arteries.

PURPOSE: To investigate the effect of melatonin on isolated porcine ciliary arteries. METHODS: Isolated porcine ciliary arteries were suspended in myograph chambers filled with modified Krebs-Ringer solution (37 degrees C; 95% O2/5% CO2) for isometric tension recording. RESULTS: In quiescent porcine ciliary arteries with endothelium, melatonin (10(-11)--10(-5) M) evoked no change in vascular tone. The highest concentration of melatonin (10(-4 ) M) evoked a small but significant contraction. In vessels precontracted with U-46619 (10(-7) M), increasing concentrations of melatonin (10(-11)--10(-5) M) did not evoke a response. In precontracted arteries with endothelium, contractile response of vascular smooth muscle to increasing concentrations of serotonin (10(-10)--10(-5) M) and noradrenaline (10(-10)--10(-5) M) was reduced after preincubation with melatonin (10(-4) M). Melatonin (10(-4) M) did not alter the response to endothelin-1 (10(-10)--10( -7) M) and U-46619 (10(-10)--10(-6 ) M) in precontracted arteries with endothelium. CONCLUSION: These findings demonstrate that melatonin attenuates the effect of serotonin and noradrenaline and is itself a mild vasoconstrictor in porcine ciliary arteries. The role of melatonin in human ocular circulation remains to be established.