Desynchronization of daily rest-activity rhythm in the days following light propofol anesthesia for colonoscopy

Anesthesia and surgery are associated with fatigue and sleep disorders, suggestive of disturbance of the circadian rest-activity rhythm. Previous studies on circadian rhythm disturbance were focused on patients undergoing general anesthesia associated with surgery. This does not permit one to draw valid conclusions about the effects of general anesthesia per se on circadian rhythms. Our study was set up to determine the impact of a hypnotic dose of propofol on the circadian rest-activity rhythm in humans under real-life conditions. Seventeen healthy subjects scheduled to receive light propofol anesthesia for ambulatory colonoscopy were investigated. Their rest-activity rhythms were assessed using actigraphic monitoring. Diurnal rest was increased, whereas nocturnal sleep was unchanged in the days following anesthesia. Nonparametric analyses showed a decrease in the strength of coupling of the rhythm to stable environmental zeitgebers and increase of fragmentation of the rhythm after anesthesia. Light general anesthesia itself impairs synchronization of the circadian rest-activity rhythm to local time in patients by acting directly on the circadian clock.     

Circadian disruption and surgical recovery

Circadian rhythms were investigated in rats following surgery, as measured by body temperature and locomotor activity, and postoperative recovery was measured by activity level. Eight randomly selected Sprague-Dawley rats were implanted with radio temperature-transmitters under general anesthesia. Timer-controlled cassette recorders recorded body temperature at predetermined intervals. To monitor activity, the rats were placed in individual metabolic cages equipped with infrared-sensitive locomotor activity monitors. Temperature was sampled hourly. Activity was measured continuously and summed every 15 minutes for sampling. Measurement was begun before surgery and continued from 12 to 20 days following surgery, depending on when the animals regained their typical rhythmic patterns. Temperature and activity rhythms were altered and uncoupled from external cues in a manner similar to that previously found in humans. The animals demonstrated individual variation in their return to presurgical activity levels. Six days after surgery, the rats experienced a second period of disrhythmic and decreased activity. Rats with the greatest activity phase-shifts took longest to return to presurgical activity levels. This suggests that the degree of circadian alteration following surgery is positively related to the time required for recovery and reentrainment of rhythmicity.     

Measuring circadian temperature rhythm

Experimental control and mathematical techniques increase confidence that results of circadian temperature rhythm studies reflect true changes in the circadian timing system versus coupling with exogenous synchronizers. Masking effects represent confounding influences in studies that are concerned with the endogenous temperature rhythm. Because it is technically difficult to measure directly the behavior of the endogenous timing system, marker rhythms are used as proxy measures. However in addition to entraining, the external environment exerts a direct masking effect on the monitored rhythm. Methods for measuring circadian temperature rhythm are reviewed in this article. Constant routine, forced desynchrony, and purification methods represent attempts, at an experimental or mathematical level, to remove masking effects and more accurately capture the endogenous circadian temperature rhythm. Exogenous factors have not been subjected to the same scrutiny as the endogenous features of circadian temperature rhythm. But it is the environmental context, the extent to which the endogenous features are adaptively modified by the field environment, that will ultimately determine the biological value of circadian temperature rhythm to the organism. Thus, nurse investigators are encouraged to use rigorous methods to study both endogenous circadian temperature rhythm and exogenous rhythms.     

Characteristics of infradian and circadian rhythms in the persistent vegetative state

This retrospective study investigated the circadian and infradian characteristics of blood pressure and heart rate in 26 patients with traumatic head injury in a persistent vegetative state (PVS). Systolic and diastolic blood pressures and heart rate were measured every hour for the first 240 h (10 days) following hospital admission. These data were analysed for the presence of circadian and infradian rhythms using the least-squares fit of the cosine function with the single cosinor method. Infradian rhythms were defined as biological rhythms with a period of approximately 7 days (circaseptan rhythms). All the patients studied had circadian and circaseptan rhythms of systolic and diastolic blood pressures and heart rate. The amplitudes of all the circaseptan rhythms were significantly greater than those of the corresponding circadian rhythms. It was concluded that there was an altered association between circadian and infradian blood pressure and heart rate rhythms in patients in a PVS. Circadian and infradian rhythms were present, but the infradian rhythm had a greater amplitude than the circadian rhythm.     

Circadian rhythm of blood pressure in normotensive NIDDM subjects. Its relationship to microvascular complications

OBJECTIVE: To investigate the relationship between circadian rhythm of mean blood pressure (MBP) and microvascular complications in non-insulin-dependent diabetes mellitus (NIDDM) subjects. RESEARCH DESIGN AND METHODS: Seventy-six normotensive NIDDM subjects without azotemia were studied under ordinary hospital conditions with a noninvasive ambulatory blood pressure monitoring device. Time series data were analyzed by the cosinor method. RESULTS: Fifty-four subjects had a circadian MBP rhythm similar to that of 34 age-matched nondiabetic control subjects, with a peak value in the afternoon (group 1). In contrast, 22 had a reversed circadian MBP rhythm, with a peak value during the night (group 2). Obvious complications were found in 65% of group 1 and in all of group 2. The prevalence of retinopathy and somatic neuropathy and the degree of retinopathy were similar in the two groups. The prevalence and degree of autonomic neuropathy (postural hypotension and reduced beat-to-beat heart-rate variation) and nephropathy were greater in group 2 than group 1. Linear discriminant analysis revealed a correlation between the reversed circadian MBP rhythm and postural hypotension (F = 32.2, P less than 0.001) and overt nephropathy (F = 5.1, P less than 0.05) but not with beat-to-beat heart-rate variation (F = 0.17, NS). CONCLUSIONS: These results suggest that in the hospitalized normotensive NIDDM subjects, there are normal and reversed circadian MBP rhythms and that the reversal of normal circadian MBP rhythm may be related to the degree of postural hypotension and/or nephropathy.     

The effect of cycled lighting in the intensive care unit on sleep,activity and physiological parameters: A pilot study

Patients in intensive care suffer from severe illnesses or injuries and from symptoms related to care and treatments. Environmental factors, such as lighting at night, can disturb patients’ circadian rhythms. The aim was to investigate whether patients displayed circadian rhythms and whether a cycled lighting intervention would impact it. In this pilot study (N = 60), a cycled lighting intervention in a two-bed patient room was conducted. An ordinary hospital room functioned as the control. Patient activity, heart rate, mean arterial pressure and body temperature were recorded. All data were collected during the patients’ final 24 h in the intensive care unit. There was a significant difference between day and night patient activity within but not between conditions. Heart rates differed between day and night significantly for patients in the ordinary room but not in the intervention room or between conditions. Body temperature was lowest at night for all patients with no significant difference between conditions. Patients in both conditions had a natural circadian rhythm; and the cycled lighting intervention showed no significant impact. As the sample size was small, a larger repeated measures study should be conducted to determine if other types of lighting or environmental factors can impact patients’ well-being.     

Effect of genetic obesity on thermoregulatory activity responses to inversion of the light/dark cycle

In this pilot work, the authors compared the circadian rhythm responses of 3-month-old female fatty Zucker rats with those of lean Zucker rats and Sprague-Dawley rats to reversal of the light/dark (LD) cycle. Core temperature and spontaneous cage activity were continuously monitored by implanted microtelemetry devices prior to and for 5 days following complete LD cycle reversal. By the 5th day after LD reversal, temperature rhythm nadir had phase-advanced 10.5 hours in the lean Zucker rats, 10.8 hours in the Sprague-Dawley rats, and only 3.8 hours in the fatty Zucker rats. Similarly, total activity increased in lean Zucker rats and Sprague-Dawley rats after LD reversal but declined in the fatty Zucker rat during the same time. Results of this study show that obese Zucker rats displayed an impaired ability to reentrain circadian rhythms for temperature and activity when compared to lean Zucker rats and Sprague-Dawley rats. These findings suggest that dysfunction in the circadian pacemaker previously shown to manifest itself by 43 weeks of age in fatty Zucker rats may already be present at 3 months of age and suggest that altered thermoregulation may play a role in the development of obesity in this animal model of genetic obesity.     

原发性高血压与生物节律的研究概况

生物节律是生命体的基本现象之一。在人类最为常见且研究最多的是昼夜节律。该文通过生物节律改变。影响昼夜节律变化的内源性因素,高血压对机体靶器官的损害以及高血压的时间治疗学来阐述生物节律与高血压的相关研究。     

Circadian and circannual rhythms of several enzymes of lysosomal origin in human plasma

The circadian and circannual group rhythms in the plasma concentrations of the following lysosomal enzymes were studied in women and men: beta-D-N-acetylglucosaminidase, beta-D-glucuronidase, beta-D-glucosidase, beta-D-galactosidase, alpha-D-galactosidase, alpha-L-fucosidase and alpha-D-mannosidase. The circadian rhythm was detected in all the tested enzymes of women, and only in alpha-D-galactosidase, beta-D-glucosidase, alpha-D-mannosidase and beta-D-N-acetylglucosaminidase of men. A statistically significant difference between genders in the circadian rhythm was exhibited by beta-D-galactosidase, beta-D-glucosidase, beta-D-N-acetylglucosaminidase, beta-D-glucuronidase, alpha-D-galactosidase and alpha-L-fucosidase. A circannual rhythm was detected in all the tested enzymes, with the exception of beta-D-glucuronidase and beta-D-N-acetylglucosaminidase, without any statistically significant difference between genders. The group rhythms of some of the enzymes (alpha-D-galactosidase, beta-D-glucosidase, beta-D-galactosidase) showed similar values of both circadian and circannual acrophases, suggesting that they may be subjected as a group to the same chronobiological coordination. The chronobiological rhythms of lysosomal enzymes were different from those of lactate dehydrogenase and alpha 1-antitrypsin, indicating that these rhythms are not merely reflecting fluctuations of the water content of plasma. No in-phase relationship was observed between the circadian and circannual rhythms of plasma cortisol and those of the tested lysosomal enzymes, excluding a direct chronobiological relationship between this hormone and lysosomal enzymes.     

Alterations in circadian excretion of urinary variables and physiological indicators of stress following surgery

Alterations in level, timing, and coupling of circadian excretion of catecholamine metabolites, adrenal cortical hormones, sodium, potassium, creatinine, and vital signs in acute-care surgical patients were measured. Data were examined to determine if a relationship exists between the degree of circadian alteration and the subject's reentrainment to typical circadian profiles. Urine samples for assay, temperature, heart rate, and blood pressure were collected daily at 2-hour intervals from 11 consenting surgery subjects and 10 age- and sex-matched control subjects. The data indicate that certain circadian rhythms of hospitalized subjects were altered and uncoupled from external stimuli. These findings suggest that nurses (1) give individualized patient care to promote reentrainment recovery; and (2) refine nursing assessment to consider individual circadian patterns.     

Crosstalk between central and peripheral biological clocks

Mammalian circadian system is multi-oscillator system. Clock gene expression analysis revealed that central clock, suprachiasmatic nucleus, organizes and synchronizes the peripheral oscillators in the whole body cells. Similarly, human circadian system is considered to be dual oscillation system because of internal desynchronization between melatonin, body temperature rhythms(driven by oscillator I) and sleep-wake rhythm (driven by oscillator II) under temporal isolation of dim light conditions. These oscillators control their periods mutually which means there is crosstalk of oscillators. Although the effect from oscillator II to oscillator I is weak under experimental dim light conditions, sleep-wake behavior controls light input to light sensitive oscillator I and feedbacks to sleep-wake driving oscillator II under lighting condition we live. To understand these mechanisms is important for prevention of circadian rhythm related diseases.     

Body-temperature circadian rhythm in 67 patients after heart valve replacement surgery secondary to valvular heart disease

PurposePatient body temperature was monitored after cardiac valve replacement, in order to explore the characteristics of body-temperature circadian rhythm and the factors influencing that rhythm.MethodsA cohort of 67 patients who received cardiac valve replacement in a Fuzhou, Fujian province, China, general hospital underwent temperature measurements and analysis (by cosine curve) of their body-temperature circadian rhythm. A biological rhythm model was established through principal component analysis and evaluation of biological rhythm features. Multiple circadian parameters were included through linear regression analysis.ResultsPatients' temperature after cardiac valve replacement exhibited circadian characteristics (p < 0.05), among which the scores of temperature mesor, amplitude, and acrophase were respectively (37.61 ± 0.08), (0.10 ± 0.09), and −33 (–355, –119). Body-temperature rhythms were influenced by both gender and cardiopulmonary bypass time (p < 0.05).ConclusionAlthough some patients' circadian characteristics disappeared after cardiac valve replacement, circadian rhythms remained intact for most patients. Measures that were found to mitigate body-temperature circadian rhythm disruption included building a natural rhythm of light/darkness and decreasing cardiopulmonary bypass time.     

Circadian regulation of cardiac metabolism

Circadian rhythm evolved to allow organisms to coordinate intrinsic physiological functions in anticipation of recurring environmental changes. The importance of this coordination is exemplified by the tight temporal control of cardiac metabolism. Levels of metabolites, metabolic flux, and response to nutrients all oscillate in a time-of-day–dependent fashion. While these rhythms are affected by oscillatory behavior (feeding/fasting, wake/sleep) and neurohormonal changes, recent data have unequivocally demonstrated an intrinsic circadian regulation at the tissue and cellular level. The circadian clock — through a network of a core clock, slave clock, and effectors — exerts intricate temporal control of cardiac metabolism, which is also integrated with environmental cues. The combined anticipation and adaptability that the circadian clock enables provide maximum advantage to cardiac function. Disruption of the circadian rhythm, or dyssynchrony, leads to cardiometabolic disorders seen not only in shift workers but in most individuals in modern society. In this Review, we describe current findings on rhythmic cardiac metabolism and discuss the intricate regulation of circadian rhythm and the consequences of rhythm disruption. An in-depth understanding of the circadian biology in cardiac metabolism is critical in translating preclinical findings from nocturnal-animal models as well as in developing novel chronotherapeutic strategies.     

Influence of bright light therapy on postoperative patients: a pilot study.

Bright light therapy is a method of maintaining or restoring the natural circadian rhythm by assisting daytime awakening using bright lights. Postoperative delirium is one of the potential complications encountered by patients receiving postoperative care in the intensive care unit (ICU), but there have been no studies on the use of light for the prevention of postoperative delirium. The objective of this study was to examine whether the circadian rhythms of patients after surgery for oesophageal cancer can be adjusted and whether the postoperative delirium crisis rate can be reduced by bright light therapy. The subjects were 11 patients operated on for oesophageal cancer in Osaka University Hospital. After informed consent was obtained, they were divided into a study group and a control group by a random sampling method. After removal of the endotracheal tube, the study group was exposed to light. The light intensity was about 5000lx immediately before the eyes, and the distance from the light source was about 100 cm. The control group was placed in a natural lighting environment after extubation. In both groups, the rhythms of physical activities and autonomic activities were monitored after surgery, and delirium was evaluated. A significant difference was observed in the delirium score between the study group and control group on the morning of day 3 of bright light therapy by the Mann-Whitney U-test (P=0.014). The study group could begin ambulation about 2 days earlier than the control group. Bright light therapy may reduce the rate of postoperative delirium and make early ambulation possible. However, our study involved a very small sample size. We want to increase the sample in the future after having reviewed clinical application methods.     

Relationship of endogenous circadian melatonin and temperature rhythms to self-reported preference for morning or evening activity in young and older people.

BACKGROUND: Morningness-eveningness refers to interindividual differences in preferred timing of behavior (i.e., bed and wake times). Older people have earlier wake times and rate themselves as more morning-like than young adults. It has been reported that the phase of circadian rhythms is earlier in morning-types than in evening types, and that older people have earlier phases than young adults. These changes in phase have been considered to be the chronobiological basis of differences in preferred bed and wake times and age-related changes therein. Whether such differences in phase are associated with changes in the phase relationship between endogenous circadian rhythms and the sleep-wake cycle has not been investigated previously. METHODS: We investigated the association between circadian phase, the phase relationship between the sleep-wake cycle and circadian rhythms, and morningness-eveningness, and their interaction with aging. In this circadian rhythm study, 68 young and 40 older subjects participated. RESULTS: Among the young subjects, the phase of the melatonin and core temperature rhythms occurred earlier in morning than in evening types and the interval between circadian phase and usual wake time was longer in morning types. Thus, while evening types woke at a later clock hour than morning types, morning types actually woke at a later circadian phase. Comparing young and older morning types we found that older morning types had an earlier circadian phase and a shorter phase-wake time interval. The shorter phase-waketime interval in older "morning types" is opposite to the change associated with morningness in young people, and is more similar to young evening types. CONCLUSIONS: These findings demonstrate an association between circadian phase, the relationship between the sleep-wake cycle and circadian phase, and morningness-eveningness in young adults. Furthermore, they demonstrate that age-related changes in phase angle cannot be attributed fully to an age-related shift toward morningness. These findings have important implications for understanding individual preferences in sleep-wake timing and age-related changes in the timing of sleep.     

A circadian rhythm of proteinuria in patients with a nephrotic syndrome

Circadian variations in proteinuria were studied in 17 patients with different types of glomerulopathies. During 3-4 successive days urine was collected over periods of 3 h under standardized conditions. Thirteen of the 17 patients showed a circadian rhythm of their proteinuria with a maximum excretion in daytime around 16.00 hours and a minimum excretion at night around 03.00 hours. In the majority of patients the urinary excretory rhythms of albumin, transferrin and immunoglobulin G were 'in phase' with each other and with the circadian rhythm of total protein excretion. Nine patients had a larger degree of rhythmicity for immunoglobulin G than for transferrin excretion. In eight of them a circadian rhythm of the selectivity index of proteinuria was seen with the lowest index at night. No relation was observed between the circadian rhythm of proteinuria and the type of glomerulopathy.     

Circadian rhythms in drug action and drug metabolism in the mouse.

The relationship between circadian rhythms in the pharmacological actions of meperidine and hexobarbital and similar rhythms in the hepatic metabolism of these drugs was examined in mice under a variety of environmental alterations to determine whether such rhythms may be causally related. The rate of metabolism of p-nitroanisole and hexobarbital by hepatic 9000 X g supernatant fractions was found to be higher at 2400 hours (middark phase) compared to 1200 hours (midlight phase). The rhythms in in vitro hexobarbital and in vivo merperidine metabolism were inversely related in time with similar rhythms in duration of hexobarbital sleep time and meperidine analgesia. Exposure of mice to continuous lighting abolished the rhythms in metabolism and response to meperidine and hexobarbital. Reversal of the usual lighting cycle inverted the rhythm in hexobarbital metablism while abolishing the rhythm in pharmacological response to hexobarbital; meperidine was similarly affected. Adrenalectomy abolished the rhythm in hexobarbital metabolism, diminished the amplitude of the circadian variation in meperidine metabolism and abolished the rhythm in hexobarbital hypnosis and meperidine analgesia. These results indicate that circadian rhythms in the action of hexobarbital and meperidine are well correlated with similar rhythms in the disposition of these drugs.     

Circadian regulation of human sleep and age-related changes in its timing, consolidation and EEG characteristics.

The light-entrainable circadian pacemaker located in the suprachiasmatic nucleus of the hypothalamus regulates the timing and consolidation of sleep by generating a paradoxical rhythm of sleep propensity; the circadian drive for wakefulness peaks at the end of the day spent awake, ie close to the onset of melatonin secretion at 21.00-22.00 h and the circadian drive for sleep crests shortly before habitual waking-up time. With advancing age, ie after early adulthood, sleep consolidation declines, and time of awakening and the rhythms of body temperature, plasma melatonin and cortisol shift to an earlier clock hour. The variability of the phase relationship between the sleep-wake cycle and circadian rhythms increases, and in old age sleep is more susceptible to internal arousing stimuli associated with circadian misalignment. The propensity to awaken from sleep advances relative to the body temperature nadir in older people, a change that is opposite to the phase delay of awakening relative to internal circadian rhythms associated with morningness in young people. Age-related changes do not appear to be associated with a shortening of the circadian period or a reduction of the circadian drive for wake maintenance. These changes may be related to changes in the sleep process itself, such as reductions in slow-wave sleep and sleep spindles as well as a reduced strength of the circadian signal promoting sleep in the early morning hours. Putative mediators and modulators of circadian sleep regulation are discussed.     

Circadian rhythm of core body temperature in subjects with chronic fatigue syndrome

The pathophysiological basis for chronic fatigue syndrome (CFS) remains poorly understood. Certain symptoms of CFS, namely fatigue, neurocognitive symptoms and sleep disturbance, are similar to those of acute jet lag and shift work syndromes thus raising the possibility that CFS might be a condition associated with disturbances in endogenous circadian rhythms. In this study, we tested this hypothesis by examining the circadian rhythm of core body temperature (CBT) in CFS and control subjects. Continuous recordings of CBT were obtained every 5 min over 48 h in a group of 10 subjects who met the Center for Disease Control (CDC) definition of CFS and 10 normal control subjects. Subjects in the two groups were age, sex and weight‐matched and were known to have normal basal metabolic rates and thyroid function. CBT recordings were performed under ambulatory conditions in a clinical research centre with the use of an ingestible radio frequency transmitter pill and a belt‐worn receiver‐logger. CBT time series were analysed by a cosinor analysis and by a harmonic‐regression‐plus‐correlated‐noise model to estimate the mean, amplitude and phase angle of the rhythm. The goodness of fit of each model was also compared using the Akaike Information Criterion (AIC) and σ². Average parameters for each group were compared by Student’s t‐test. By cosinor analysis, the only significant difference between CFS and control groups was in the phase angle of the third harmonic (P=0·02). The optimal harmonic‐regression‐plus‐correlated‐noise models selected were ARMA(1,1): control 7, CFS 6; ARMA(2,0): control 1, CFS 4; and ARMA(2,1): control 2 subjects. The optimal fit ARMA model contained two harmonics in eight of 10 control subjects but was more variable in the CFS subjects (1 harmonic: 5 subjects; 2 harmonics: 1 subject; 3 harmonics: 4 subjects). The goodness of fit measures for the optimal ARMA model were also better in the control than the CFS group, but the differences were not statistically significant. We conclude that, measured under ambulatory conditions, the circadian rhythm of CBT in CFS is nearly indistinguishable from that of normal control subjects although there was a tendency for greater variability in the rhythm. Hence, it is unlikely that the symptoms of CFS are because of disturbance in the circadian rhythm of CBT.     

CLUSTER AND TRIGEMINAL AUTONOMIC CEPHALALGIAS

The suprachiasmatic nucleus (SCN) of the hypothalamus has been termed the master circadian pacemaker of mammals. Recent discoveries of damped circadian oscillators in other tissues have led to the hypothesis that the SCN synchronizes and sustains daily rhythms in these tissues. We studied the effects of constant lighting (LL) and of SCN lesions on behavioral rhythmicity and Period 1 (Per 1) gene activity in the SCN and olfactory bulb (OB). We found that LL had similar effects on cyclic locomotor and feeding behaviors and Per 1 expression in the SCN but had no effect on rhythmic Per 1 expression in the OB. LL lengthened the period of locomotor and SCN rhythms by approximately 1.6 hr. After 2 weeks in LL, nearly 35% of rats lost behavioral rhythmicity. Of these, 90% showed no rhythm in Per 1-driven expression in their SCN. Returning the animals to constant darkness rapidly restored their daily cycles of running wheel activity and gene expression in the SCN. In contrast, the OB remained rhythmic with no significant change in period, even when cultured from animals that had been behaviorally arrhythmic for 1 month. Similarly, we found that lesions of the SCN abolished circadian rhythms in behavior but not in the OB. Together, these results suggest that LL causes the SCN to lose circadian rhythmicity and its ability to coordinate daily locomotor and feeding rhythms. The SCN, however, is not required to sustain all rhythms because the OB continues to oscillate in vivo when the SCN is arrhythmic or ablated.
Comments: As the central generator for cluster appears to be near the hypothalamic circadian nuclei (May A, Bahra A, Buchel C, Frackowiak RS, Goadsby PJ. PET and MRA findings in cluster headache and MRA in experimental pain. Neurology. 2000;55:1328-1335), it behooves us to follow the work on understanding the training of circadian and circannual rhythms in order to better understand cluster. Stewart J. Tepper