The Adjustment of the Circadian Rhythm of Body Temperature to Simulated Time-Zone Transitions: A Comparison of the Effect of Using Raw Versus Unmasked Data

Deep body temperature and sleep/activity diaries data were recorded during control days and for 6 days after simulated time zone transitions of 8 h to the east (six subjects) or west (seven subjects). Circadian rhythms were assessed by cosinor analysis of both raw data (the conventional method) and purified data (corrected for the effects of sleep and activity). Analysis of raw data gives misleading information about the phase and amplitude of the rhythms due to the masking effects of the exogenous component. Use of purified data indicates that during the process of adjustment after an eastward shift (a) phase changes are more erratic than after a shift to the west; (b) no marked decrease in the amplitude of the rhythms is evident; and (c) no clear evidence exists that the circadian rhythm breaks up temporarily. The masking effect was less after the time zone transition if sleep maintenance was poor.     

The Circadian Rhythm of Body Temperature of the Horse

Rectal temperature of 10 female adult horses was recorded every 2 h for 10 consecutive days under a natural winter photoperiod (9 h of light and 15 h of darkness per day). A robust daily rhythm of body temperature was observed in all animals. The rhythm had a mean level of 38.3°C and a range of excursion of 1.0°C. Temperature started its daily ascent at dawn each day and reached a maximum 14 hours later. Body temperature of 5 of the horses was studied for 10 more days under constant illumination. The rhythm persisted under this condition, although with a slightly longer period of 24.2 h, which confirms the endogenous nature of the rhythm. Despite the fact that the body size of the horse is several orders of magnitude greater than that of rodents, the various parameters of the body temperature rhythm of the horse are similar to those of several species of rodents previously studied.     

The Circadian Rhythm of Body Temperature of the Horse

Rectal temperature of 10 female adult horses was recorded every 2 h for 10 consecutive days under a natural winter photoperiod (9 h of light and 15 h of darkness per day). A robust daily rhythm of body temperature was observed in all animals. The rhythm had a mean level of 38.3°C and a range of excursion of 1.0°C. Temperature started its daily ascent at dawn each day and reached a maximum 14 hours later. Body temperature of 5 of the horses was studied for 10 more days under constant illumination. The rhythm persisted under this condition, although with a slightly longer period of 24.2 h, which confirms the endogenous nature of the rhythm. Despite the fact that the body size of the horse is several orders of magnitude greater than that of rodents, the various parameters of the body temperature rhythm of the horse are similar to those of several species of rodents previously studied.     

The Circadian Body Temperature Rhythm in the Elderly: Effect of Single Daily Melatonin Dosing

The present study is part of a more extensive investigation dedicated to the study and treatment of age‐dependent changes/disturbances in the circadian system in humans. It was performed in the Tyumen Elderly Veteran House and included 97 subjects of both genders, ranging from 63 to 91 yrs of age. They lived a self‐chosen sleep‐wake regimen to suit their personal convenience. The experiment lasted 3 wks. After 1 control week, part of the group (n=63) received 1.5 mg melatonin (Melaxen?) daily at 22:30 h for 2 wks. The other 34 subjects were given placebo. Axillary temperature was measured using calibrated mercury thermometers at 03:00, 08:00, 11:00, 14:00, 17:00, and 23:00 h each of the first and third week. Specially trained personnel took the measurements, avoiding disturbing the sleep of the subjects. To evaluate age‐dependent changes, data obtained under similar conditions on 58 young adults (both genders, 17 to 39 yrs of age) were used. Rhythm characteristics were estimated by means of cosinor analyses, and intra‐ and inter‐individual variability by analysis of variance (ANOVA). In both age groups, the body temperature underwent daily changes. The MESOR (36.38±0.19°C vs. 36.17±0.21°C) and circadian amplitude (0.33±0.01°C vs. 0.26±0.01°C) were slightly decreased in the elderly compared to the young adult subjects (p<0.001). The mean circadian acrophase was similar in both age groups (17.19±1.66 vs. 16.93±3.08 h). However, the inter‐individual differences were higher in the older group, with individual values varying between 10:00 and 23:00 h. It was mainly this phase variability that caused a decrease in the inter‐daily rhythm stability and lower group amplitude. With melatonin treatment, the MESOR was lower by 0.1°C and the amplitude increased to 0.34±0.01°C, a similar value to that found in young adults. This was probably due to the increase of the inter‐daily rhythm stability. The mean acrophase did not change (16.93 vs. 16.75 h), although the inter‐individual variability decreased considerably. The corresponding standard deviations (SD) of the group acrophases were 3.08 and 1.51 h (p<0.01). A highly significant correlation between the acrophase before treatment and the phase change under melatonin treatment indicates that this is due to a synchronizing effect of melatonin. Apart from the difference in MESOR, the body temperature rhythm in the elderly subjects undergoing melatonin treatment was not significantly different from that of young adults. The data clearly show that age‐dependent changes mainly concern rhythm stability and synchronization with the 24 h day. A single daily melatonin dose stabilizes/synchronizes the body temperature rhythm, most probably via hypothermic and sleep‐improving effects.     

Evening Alcohol Consumption Alters the Circadian Rhythm of Body Temperature

To the Editor: Recordings of body temperature rhythms are used as a marker of the circadian system in many fields of study, including shift work, jet lag, affective disorders, gerontology, and sleep disorders. In our studies of circadian rhythms, we routinely prohibit subjects from drinking alcohol because of findings published in 1933 (1). That study found that after alcohol consumption the nocturnal temperature minimum during sleep occurred earlier, and was higher, than on control nights. In the years since that report, there have been no other studies of how alcohol changes the temperature waveform during sleep, despite other studies of the dose- and time-dependent effects of ethanol in humans (2). We decided to investigate whether the results of the 1933 report would generalize to other subjects and to women.     

The Effects of Thoracic and Cervical Spinal Cord Lesions on the Circadian Rhythm of Core Body Temperature

Individuals with a spinal cord injury (SCI) have compromised afferent and efferent information below the lesion. Intact afferent information regarding skin temperature and the ability to regulate skin blood flow lead to an altered heat balance, which may impact the circadian variation in core body temperature (Tcore) and sleep-wake cycle. The authors assessed the circadian variation of Tcore in SCI individuals and able-bodied controls matched for the timing of the sleep-wake cycle. The authors examined subjects who had a high (cervical) or a low (thoracic) lesion. Intestinal Tcore (telemetry system) and physical activity (ambulatory activity monitor) levels were measured continuously and simultaneously in 8 tetraplegics, 7 paraplegics, and 8 able-bodied controls during one 24-h period of “normal” living. The regression slope between activity and Tcore was also calculated for each 2-h bin. Circadian rhythm parameters were estimated with partial Fourier time-series analysis, and groups were compared with general linear models, adjusted for the influence of individual wake-time. The (mean?±?SD) dominant period length for controls, paraplegics, and tetraplegics were 24.4?±?5.4?h, 22.5?±?5.0?h, and 16.5?±?5.1?h, respectively (p?=?.02). A significantly more pronounced 8-h harmonic was found for the variation in Tcore of SCI individuals (p = .05). Tetraplegics showed the highest nocturnal mean Tcore (p = .005), a 5-h phase-advanced circadian trough time (p = .04), and more variable relationships between physical activity and Tcore (p = .03). Taken together, tetraplegics demonstrate a pronounced disturbance of the circadian variation of Tcore, whereas the variation of Tcore in paraplegics was comparable to able-bodied controls. (Author correspondence: D.Thijssen@fysiol.umcn.nl)     

生理节律与日常活动对人体疲劳程度的影响

目的:研究生理节律和日常活动分别对人体疲劳程度的影响大小。方法:选取某校7名大学生志愿者,在军训期间对每日军训科目严格限制条件下进行该实验,以闪光临界融合频率、心率变异性、反应时、静态姿势图TLX-NASA量表评分作为指标,对每天分别在训练前和训练后疲劳程度的大小进行测量,以这些指标描述训练前后的疲劳程度。结果:反应时降低(0.60±0.09)、反应正确率提高(0.97±0.03);闪光临界光融合频率升高(40.84±2.14);心率变异性TP(3076.60±382.08)降低、心率变异性SDNN(55.28±16.85)降低;静态姿势图晃动减少,中低频率段(0.15±0.01)、前后方向重心变位(7.92±0.63),TLX-NASA量表评分降低(30.47±10.23)。以上差异均具有统计学意义(P<0.05)。结论:生理节律相对于日常活动对机体的疲劳状态有更大的影响。     

The Shape of the Endogenous Circadian Rhythm of Rectal Temperature in Humans

Fourteen healthy subjects have been studied in an isolation unit while living on a 30h “day” (20h awake, 10h asleep) for 14 (solar) days but while aware of real time. Waking activities were sedentary and included reading, watching television, and so forth. Throughout, regular recordings of rectal temperature were made, and in a subgroup of 6 subjects, activity was measured by a wrist accelerometer. Temperature data have been subjected to cosinor analysis after “purification,” a method that enables the endogenous (clock-driven) and exogenous (activity-driven) components of the circadian rhythm to be assessed. Moreover, the protocol enables effects due to the circadian rhythm and time-since-waking to be separated. Results showed that activity was slightly affected by the endogenous temperature rhythm. Also, the masking effects on body temperature exerted by the exogenous factors appeared to be less than average in the hours before and just after the peak of the endogenous temperature rhythm. This has the effect of producing a temperature plateau rather than a peak during the daytime. The implications of this for mental performance and sleep initiation are discussed. (Chronobiology International, 13(4), 261-271, 1996)     

A Mathematical Method for Studying the Endogenous Component of the Circadian Temperature Rhythm and the Effect of Aging

A mathematical model was developed in order to study the endogenous component of the circadian rhythm in body temperature. The model describes the fluctuations in body temperature as a function of a cosine-shaped endogenous rhythm plus an exogenous component which is linearly correlated with the time spent in active wakefulness. The model was evaluated in 4 young and 4 old rats. In 7 out of 8 rats there was a significant lack of fit when the traditional cosinor method was used, as compared with only 1 out of 8 when using our model. In all 8 rats the regression was highly significant and also useful as defined by the ? m criterion. The results from the model were in agreement with literature regarding constant routine studies in humans. The mean amplitude of the endogenous rhythm was 0.24°C in young rats and 0.19°C in old rats, whereas the amplitudes of the overt rhythm were 0.38 and 0.26°C, respectively. The age-related differences in the amplitude of the overt circadian temperature rhythm could to a large extent be attributed to age-related differences in activity-induced heat production. Finally, the acrophase of the endogenous rhythm occurred 18.7 minutes later than that of the overt rhythm. If applicable to human, the proposed method may form a valuable extension to existing constant routine protocols for studying the endogenous circadian rhythm in body temperature.     

The Circadian Rhythm of Core Temperature: Origin and some Implications for Exercise Performance

This review first examines reliable and convenient ways of measuring core temperature for studying the circadian rhythm, concluding that measurements of rectal and gut temperature fulfil these requirements, but that insulated axilla temperature does not. The origin of the circadian rhythm of core temperature is mainly due to circadian changes in the rate of loss of heat through the extremities, mediated by vasodilatation of the cutaneous vasculature. Difficulties arise when the rhythm of core temperature is used as a marker of the body clock, since it is also affected by the sleep‐wake cycle. This masking effect can be overcome directly by constant routines and indirectly by “purification” methods, several of which are described. Evidence supports the value of purification methods to act as a substitute when constant routines cannot be performed. Since many of the mechanisms that rise to the circadian rhythm of core temperature are the same as those that occur during thermoregulation in exercise, there is an interaction between the two. This interaction is manifest in the initial response to spontaneous activity and to mild exercise, body temperature rising more quickly and thermoregulatory reflexes being recruited less quickly around the trough and rising phase of the resting temperature rhythm, in comparison with the peak and falling phase. There are also implications for athletes, who need to exercise maximally and with minimal risk of muscle injury or heat exhaustion in a variety of ambient temperatures and at different times of the day. Understanding the circadian rhythm of core temperature may reduce potential hazards due to the time of day when exercise is performed.     

Effect of Ambient Temperature on the Body Temperature Rhythm of Male Gray Mouse Lemurs (Microcebus murinus)

In order to cope with the seasonal variations in ambient temperature and food availability in the natural habitat, gray mouse lemurs (Microcebus murinus) exhibit adaptive energy-saving mechanisms similar to those in hibernating species with seasonal and daily heterothermia. To determine thermoregulatory responses, via telemetry we recorded body temperature and locomotor activity variations during the breeding season in three captive male mouse lemurs kept at ambient temperatures (T_a) ranging from 18° to 34°C. Rhythms in body temperature and locomotor activity were clearly exhibited regardless of ambient temperature. As _a increased, mean body temperature increased from 36.5 ± 0.1°C to 37.6 ± 0.3°C, with significant change in the amplitude of the body temperature rhythm when _a rose above 28°C. Effects of _a were mostly due to changes in the fall in body temperature occurring daily at the beginning of the light phase when the subjects entered diurnal sleep. The daily decrease in body temperature was not modified by exposure to ambient temperatures from 18°C to 28°C whereas it disappeared under warmer condition. Changes in locomotor activity levels only delayed the occurrence of thermoregulatory modulation. These results strongly suggest that, during the breeding season, the thermoneutral zone of mouse lemurs is close to 28°C and that the diurnal fall in body temperature could be considered as an important adaptive energy-saving mechanism adjusted to ecological constraints.     

The Relation of Shift Work Tolerance to the Circadian Adjustment

The amplitude and phasing of circadian rhythms are under discussion as possible predictors of tolerance to night work. In a field study, subjective sleepiness and oral temperature of 147 female nurses were measured at 2-hour intervals during a period with one morning shift and two consecutive night shifts. The nurses also filled out a questionnaire. Two types of tolerance indices were constructed: The “health index” was based on questions referring to general fatigue, gastrointestinal symptoms, and sleep disturbances, and the “sleepiness index” on the actual subjective ratings of sleepiness. According to the health index, the group with good tolerance had a larger circadian amplitude of the oral temperature rhythm on the day of the morning shift than the group with poor tolerance. However, with regard to the sleepiness index, the corresponding difference between the groups with good or poor tolerance was not significant. The data did not confirm the hypothesis that predicts a quick adjustment of the circadian rhythm when the circadian amplitude is small before the change to night work. The contradictory results found in this and in other studies do not yet permit prediction of tolerance to night work.     

The Relation of Shift Work Tolerance to the Circadian Adjustment

The amplitude and phasing of circadian rhythms are under discussion as possible predictors of tolerance to night work. In a field study, subjective sleepiness and oral temperature of 147 female nurses were measured at 2-hour intervals during a period with one morning shift and two consecutive night shifts. The nurses also filled out a questionnaire. Two types of tolerance indices were constructed: The “health index” was based on questions referring to general fatigue, gastrointestinal symptoms, and sleep disturbances, and the “sleepiness index” on the actual subjective ratings of sleepiness. According to the health index, the group with good tolerance had a larger circadian amplitude of the oral temperature rhythm on the day of the morning shift than the group with poor tolerance. However, with regard to the sleepiness index, the corresponding difference between the groups with good or poor tolerance was not significant. The data did not confirm the hypothesis that predicts a quick adjustment of the circadian rhythm when the circadian amplitude is small before the change to night work. The contradictory results found in this and in other studies do not yet permit prediction of tolerance to night work.     

The Application of Linear Piecewise Regression to Basal Body Temperature Data

In many situations one wishes to fit a piecewige regression which enables one to obtain estimates of the join points as well as the slopes and intercepts of the fitted submodels. This study developes a technique for fitting piecewise models to data which contain measurement error in an independent variable. The technique developed here combines the HUDSON (1966) procedure for estimating parameters in piecewise regression and the WALD (1940) Grouping Technique which obviates the problem of measurement error. If one assumes some knowledge of the position of the join point in relation to the data, methodology has been developed to estimate the parameters and study the asymptotic properties of the means and variances of the parameter estimates. However, in the more realistic case, when additional knowledge is limited, it is only possible to obtain the parameter estimates using an iterative technique (TEETER, 1982). The general technique for obtaining the join point estimate in the presence of measurement error is presented here and an example is given using data on women's basal body temperature during menstrual cycles.     

The Effect of Activity on the Waking Temperature Rhythm in Humans

Nine healthy female subjects were studied when exposed to the natural light-dark cycle, but living for 17 “days” on a 27h day (9h sleep, 18h wake). Since the circadian endogenous oscillator cannot entrain to this imposed period, forced desynchronization between the sleep/activity cycle and the endogenous circadian temperature rhythm took place. This enabled the effects of activity on core temperature to be assessed at different endogenous circadian phases and at different stages of the sleep/activity cycle. Rectal temperature was measured at 6-minute intervals, and the activity of the nondominant wrist was summed at 1-minute intervals. Each waking span was divided into overlapping 3h sections, and each section was submitted to linear regression analysis between the rectal temperatures and the total activity in the previous 30 minutes. From this analysis were obtained the gradient (of the change in rectal temperature produced by a unit change in activity) and the intercept (the rectal temperature predicted when activity was zero). The gradients were subjected to a two-factor analysis of variance (ANOVA) (circadian phase/ time awake). There was no significant effect of time awake, but circadian phase was highly significant statistically. Post hoc tests (Newman-Keuls) indicated that gradients around the temperature peak were significantly less than those around its trough. The intercepts formed a sinusoid that, for the group, showed a mesor (±SE) of 36.97 (±0.12) and amplitude (95% confidence interval) of 0.22°C (0.12°C, 0.32°C). We conclude that this is a further method for removing masking effects from circadian temperature rhythm data in order to assess its endogenous component, a method that can be used when subjects are able to live normally. We suggest also that the decreased effect of activity on temperature when the endogenous circadian rhythm and activity are at their peak will reduce the possibility of hyperthermia.     

Adaptation of the Human Body to Simulated Weightlessness: Clinical Studies

Problems of adaptation of functional systems of the human body to conditions of continuous weightlessness are considered (prolonged stay under conditions of antiorthostatic hypokinesia and in an immersion medium). It was revealed that, during adaptation to these conditions, polymorphic clinicofunctional disorders develop, transforming into clinicophysiological syndromes, the most frequently observed being autonomic vascular malfunction, asthenoneurotic syndrome, detraining of the blood circulatory system, trophic and neuromuscular disorders, statokinetic syndrome, pain syndrome, and metabolic and hormonal disorders. The severity of the specified disorders and the duration of the recovery period depend on the duration of hypokinesia and the intensity and regularity of application of preventive measures during hypokinesia. The most probable pathophysiological mechanisms of adverse effects of continuous hypokinesia (maladaptation) on functional systems of the human body are described.     

Circadian Reactivity Rhythm of Rat Gastric Mucosa to Restraint-Cold Stress and Indomethacin: Temporal Variation in the Protective Effect of Iloprost

In this study, the time-dependent ulcerogenic effects of restraint-cold stress and indomethacin on the gastric mucosa and the temporal variation in the protective effect of iloprost, a synthetic stable analog of prostacyclin, were investigated in rats synchronized to 12h light and 12h darkness, lights on at 08:00. The severity of gastric ulceration produced by either stress or indomethacin showed marked circadian variation; it was greatest at 11 HALO (hours after lights on) for restraint-cold stress and at 23 HALO for indomethacin. The severity of the induced ulcerogenesis was least at 7 HALO for both stimuli. The protective effect of iloprost against restraint-cold stress was most prominent at 15 HALO and 19 HALO with an approximately 80% protection score. On the other hand, pretreatment with iloprost reduced the indomethacin-induced mucosal injury only at 23 HALO. The circadian variation in the effect of iloprost and in the rhythmic modalities of these two experimental ulcer models are indicative of differences in their underlying mechanisms. In experimental models of ulceration, the circadian time of application of the ulcerogenic stimulus must be considered as an important experimental factor. Moreover, the protective effectiveness of antiulcer drugs can express time-dependent differences and must also be taken into account in investigative research. (Chronobiology International, 14(6), 575–583, 1997)     

The Circadian Rhythm of Stomatal Opening: Evidence for the Involvement of Potassium and Chloride Fluxes

Epidermal strips were taken from plants of Commelina communisat opposite phases of an entrained circadian rhythm, at timeswhich corresponded to the middle of the day phase and the middleof the night phase. Earlier observations of much reduced openingin response to external stimuli in the night phase were confirmed. Evidence is now presented that uptake or retention of specificions by the guard cells is affected by the phase of the rhythm.The overt expression of the rhythm was reduced if the epidermiswas presented with potassium iminodiacetate instead of potassiumchloride. Iminodiacetate is a non-absorbable anion, and thisresult suggested that chloride uptake is important for the fullexpression of the rhythm. The use of an anion channel inhibitor(DIDS) gave strong support for this conclusion. Reduced uptakeof chloride would explain an earlier observation that formationof malate is greater during the night phase. When the guard cells were presented with sodium chloride insteadof potassium chloride there was still an overt expression ofthe rhythm, but this was of reduced magnitude. This suggeststhat potassium movements might contribute to the rhythm, andstudies of ionic fluxes using ⁸⁶Rb as a tracer showed greatereffluxes during the night phase. It is concluded that the circadian rhythm in stomatal openingmay be the result of a varying ability of the guard cells toaccumulate or retain both chloride and potassium ions. Key words: Circadian rhythm, stomatal opening, Commelina communis, potassium and chloride fluxes