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Circadian rhythm of rectal temperature in humans under different ambient temperature cycles
Journal of Thermal Biology 27 (2002) 439–447
Circadian rhythm of rectal temperature in humans under different ambient temperature cycles Tomoko Wakamura*,1, Hiromi Tokura2 Department of Environmental Health, Nara Women’s University, Nara 630-8506, Japan Received 27 July 2001; accepted 29 January 2002
Abstract 1. The present study is aimed at knowing whether ambient temperature (Ta ) cycles exert any influence on circadian rhythm of rectal temperature (Tre ) in humans. 2. Three different Ta conditions were provided: (1) Ta was kept constant at 251C for 24 h (Constant). (2) Ta decreased from 251C to 221C over 4 h from 1800 to 2200 h, was then kept constant at 221C for additional 6 h and increased to 251C over 4 h from 0400 to 0800 h (FLR). (3) Ta was changed reversibly from 251C through 281C to 251C with identical time schedule like FLR (RHF). 3. Minimum level and evening decreasing rate/morning increasing rate in Tre were significantly the lowest and greatest in FLR. r 2002 Elsevier Science Ltd. All rights reserved. Keywords: Humans; Circadian rhythm; Rectal temperature; Skin temperatures; Ambient temperature cycle
1. Introduction Light and ambient temperature (Ta ) play an important role as Zeitgeber for circadian rhythm from unicellular organisms to higher animals (see Rusak and Zucker, 1979; Rensing et al., 1995). Thermoregulation in ectotherms (poikilotherms) such as reptiles depends on Ta (Firth et al., 1999) and their circadian rhythms of locomotor and pineal gland activities are entrained by the Ta cycles (Underwood, 1985). On the other hand, thermoregulation in endotherms (homeotherms) maintains steady-state conditions by balancing metabolic heat production and heat loss (Aschoff, 1958), their internal regulation of body temperature being more *Corresponding author. Fax: +81-78-925-0878. E-mail address: tomoko [email protected] (T. Wakamura). 1 Present address: College of Nursing Art & Science, Hyogo, Akashi 673-8588, Japan. 2 Present address: Dept. of Working Physiology and Ergonomics, Nofer Institute of Occupational Medicine, Łodz, Poland.
autonomous than that of poikilotherms. It is widely reported that there are temperature compensation mechanisms for the function of circadian pacemakers (Sweeney and Hastings, 1960), and the temperature coefficient (Q10) is closer to 1.0 in humans (Rawson, 1960). Even though, in some primates, circadian locomotor rhythms have been entrained by the Ta cycles (Tokura and Aschoff, 1983; Aschoff and Tokura, 1986), such cycles have been considered less effective as Zeitgeber than the light–dark cycles (Aschoff, 1999). This result also accords with the observation that, although the photoperiod and Ta cycles act together to entrain the circadian rhythm of melatonin secretion in fish, the temperature cycles were less effective than the ! et al., 1994). photoperiod (Falcon However, recently, Liu et al. (1998) found that Ta was a more effective entraining agent than light in Neurospora. Also, Robinson and Fuller (1999) demonstrated that the free-running circadian period (t) of the squirrel monkeys was shorter when they were studied in mild cold conditions rather than in the thermoneutral zone. Just as light–dark cycles exist in natural condition, so also do the Ta cycles; that is, the Ta at midday is higher
0306-4565/02/$ - see front matter r 2002 Elsevier Science Ltd. All rights reserved. PII: S 0 3 0 6 - 4 5 6 5 ( 0 2 ) 0 0 0 1 4 - 1
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T. Wakamura, H. Tokura / Journal of Thermal Biology 27 (2002) 439–447
than that at midnight (solar time). In humans, Aschoff and Heise (1972) showed that the range of oscillation in rectal temperature depended on Ta (ranging from 201C to 321C). In addition, Wever (1979) demonstrated in humans that t; measured under conditions when Ta was self-controlled, was significantly longer than when it was measured under conditions of a constant Ta (24.91C). Most studies do not seem to have considered the possible influence of the day–night variation of Ta within the thermoneutral zone. Teramoto et al. (1998) have found that temperature cycles have profound influence upon the behaviors of core body temperature during night sleep. They found that a gradual decrease in room temperature from 271C to 25.51C over the 4 h from midnight to 0400 h, and then a gradual increase from 25.51C to 271C over the 4 h from 0400 to 0800 h (Fall–Rise) caused a further decrease in core body temperature, and was accompanied by the feeling of a better sleep, when compared with opposite changes of room temperature (Rise–Fall). The authors considered that these findings indicated that changes in room temperature affected the circadian variation in the set-point of core body temperature, and that they could induce a deeper nocturnal fall of core body temperature. However, if this hypothesis is true, it is essential to measure the core body temperature over 24-h period under the influence of Ta cycles that mimic the circadian change of set-point in core temperature, because this setpoint varies in a circadian manner (Aschoff, 1970; Cabanac et al., 1976). Bearing these considerations in mind, our present experiment has been aimed at investigating how the circadian rhythm of core body temperature could be influenced by changes within the thermoneutral zone of the Ta cycle.
2. Methods 2.1. Participants Nine female students were screened in terms of general medical and psychological health. Their physical characteristics were as follows: age, 21.871.8 (SD) yr (range 19–24); height, 1.6070.04 (SD) m (range 1.54– 1.66); weight, 53.778.6 (SD) kg (range 44–68); body mass index, 21.0072.67 (SD) kg/m2 (range 17.18–24.24) (BMI; weight/height2); and body surface area, 1.5070.12 (SD) m2 (range 1.38–1.69) [calculated, with weight in kg and height in cm, as weight0.444 height0.663 88.83 cm/kg]. They had no self-reported sleep disorders and none were smokers. At the time of the study, they were in the follicular phase of their regular menstrual cycle as indicated by their basal body temperature.
The Ethic and Research Committee of Nara Women’s University approved the experimental protocol. The nature, purpose, and risks of the study were explained before participants gave their written consent. They were permitted to stop the experiment at any time whenever they wished to do so; however, all the participants completed the study without complaint.
2.2. Experimental protocol The experiments were carried out between May and July 2000. Participants were instructed to adhere to their regular sleep schedules (sleep between 0000 h730 min and 0800 h730 min) before the experiment. They were required to refrain from heavy physical activity during the day before entering the experimental chamber. The participants entered the experimental chamber at 1000 h. The room was controlled for temperature, humidity (60% RH) and light, and was isolated from external sound and light. They stayed in the room for 3 days (see Fig. 1 for the experimental protocol). The Ta during the first daytime, the day of entry, was kept constant at 251C (Constant). During the subsequent nights, the Ta between 2200 and 0400 h was set randomly to 2270.21C or 2870.61C. In the 221C condition, the temperature was lowered to this value from the control value of 251C at 1800 h, and was raised back to this control value at 0400 h (see Fig. 1), mimicking the natural nocturnal fall and rise of Ta : This was called Fall–Low–Rise (FLR) condition. When the temperature was raised to 281C, the time course of the changes was similar; this was called the Rise–High– Fall (RHF) condition. The changes in room temperature, with the exception of the first (control) day, were counterbalanced. Lighting was controlled to mimic the natural light condition. Participants were exposed to 5000 lx from 0800 to 1500 h and 200 lx from 1800 to 0000 h. Time of lights-off and retiring to bed were standardized throughout, time in bed being from 0000 to 0800 h. In addition, from 1900 h (after their meal) to 0000 h, participants were required to adopt a semi-Fowler’s position in order to minimize the differences of heat loss due to physiological posture changes, their head elevated to about 451 angle, using a reclining chair. The experiment commenced with the application of the rectal and skin temperature probes. Meals were provided at 0830, 1200 and 1800 h; total calorie intake was 7531 kJ/day, a value calculated to balance daily energy expenditure. These meals had the same composition for all the participants. Water was available at any time. Reading, writing, and talking (although none of these were permitted to be overstimulating) were allowed during the experiment.
T. Wakamura, H. Tokura / Journal of Thermal Biology 27 (2002) 439–447
441
Rise-High-Fall
Ambient Temperature Cycle (°C)
Sleep
6,000
Fall-Low-Rise
5,000 28 4,000 25
3,000 2,000
22
Light Intensity Cycle (lx)
Constant
31
1,000 19
0 8
10
12
14
16
18
20
22
0
2
4
6
8
Meal Fig. 1. Experimental schedule: (–K–) Rise–High–Fall (RHF); (—) Constant; (–J–) Fall–Low–Rise (FLR) conditions during a day. Light intensity: light gray color (right vertical axis). Meal times: 0830, 1200 and 1800 h. On the first day, the condition selected was Constant. On the subsequent days, the conditions were RHF or FLR in a counter-balanced design.
The clothing worn was a short-sleeved shirt and kneelength pants made of 100% cotton, and no socks; this was chosen according to Park and Tokura (1997). At night, the same clothing was worn and with the addition of bath towel. 2.3. Data acquisition Temperatures (rectal and skin) were continuously recorded by a logger (LT-8A, Gram, Japan), every 1 min and were averaged later, every 30 min. Rectal temperature (Tre ) as a measure of core body temperature was recorded by a thermistor probe (LT-ST08-11, accuracy70.011C; Gram, Japan) inserted 10 cm past the anal sphincter. Skin temperatures were also recorded by thermistor probes (LT-ST08-12, accuracy70.011C; Gram, Japan) fixed to the skin with thin, air-permeable adhesive surgical tape (Surgical tape, Nichban, Japan). Skin temperatures were measured at eight sites as follows: mid-forehead (Tfh ), abdomen, (Tab ), left and right (later averaged) centers of the back of the hand (Thand ), middle, left and right (later averaged) centers of the instep of the foot (Tfoot ), left leg (Tleg ) and mid-thigh on the rectus femoris muscle (Tthigh ). 2.4. Data analysis Raw data of temperatures were inspected visually and segments that had been lost (due to slippage of the temperature sensor) were estimated by interpolation. Raw data from each participant were averaged over 30 min. Maximum and minimum values of rectal temperatures and the time when those occurred were
individually derived from cosine curve analysis of the raw data, and their average values were compared. Differences over time between the three Ta conditions were analyzed by using a two-way analysis of variance (ANOVA) with repeated measures. Interactions (condition time) were also assessed. The ANOVA was applied separately for three periods: 1800– 2200, 2200– 0400, and 0400–0800 h. Huynh–Feldt (H–F) statistics were used to adjust the covariance matrix for violations of sphericity (Mauchly). Though p values of H–F were based on corrected degrees of freedom, the original degrees of freedom were used. When the F ratio proved significant, Tukey’s and Dunnett’s multiple post hoc tests were applied to locate a significant difference between the means. The maximum and minimum values, their timing, and their differences were extracted from this analysis. Data were expressed usually as means7SEM. po0:05 was used to define significance.
3. Results Fig. 2 shows a comparison of 24 h rhythms in: upper, rectal temperature (Tre ); middle, mid-forehead skin temperature (Tfh ) and bottom, abdomen skin temperature (Tab ) among Constant, RHF and FLR conditions. Average maximum and minimum values of Tre were obtained from individual cosine curves fitted to the raw data. The average maximum Tre values were 37.2770.021C (mean7SD), 37.3170.011C and 37.3170.041C in Constant, FLR and RHF conditions. These were not significantly different (Table 1). The
T. Wakamura, H. Tokura / Journal of Thermal Biology 27 (2002) 439–447
442
Sleep
Tre
NS
**
37.6 37.4 37.2 37 36.8 36.6 36.4 36.2 36 35.8 35.6 35.4 8
Tfh
NS
10
12
14
16
18
20
22
0
**
36 35.5 35 34.5 34 33.5 33 32.5 32 31.5 31 8
10
12
14
16
18
20
4
**
22
0
NS
36.5
2
6
8
**
2
4
6
8
NS
**
36
Tab
35.5 35 34.5
Rise-High-Fall Constant Fall-Low-Rise
34
**
33.5 8
10 12 14 16 18 20 22
0
2
4
6
8
Fig. 2. Rectal (upper), mid-forehead (middle) and abdomen (lower) temperatures (mean7SEM) during the three different Ta cycles: sleep time (0000–0800 h) indicated by arrows; (–K–) Rise–High–Fall (RHF); (—) Constant; (–J–) Fall–Low–Rise (FLR) conditions; po0:01 (n ¼ 9).
average minimum Tre values were 36.3970.041C, 36.3070.071C and 36.6970.081C in Constant, FLR and RHF conditions (Table 1), which were significantly different among the three conditions (F ¼ 10:7; d.f.=2, 16, po0:01). Minimum Tre was not significantly different between FLR and Constant conditions
(p ¼ 0:57), but was significantly different (po0:01) between RHF and FLR and was also significantly different (po0:01) between RHF and Constant conditions. The nadir times of Tre were 0046 h712 min, 0351 h711 min and 0645 h79 min in Constant, FLR and RHF conditions, respectively, which were significantly different among the three conditions (F ¼ 12:1; d.f.=2, 16, po0:01). Whereas Tre did not differ from 1800 to 2200 h among three conditions, Tre was the lowest in the FLR condition and the highest in the RHF condition (F ¼ 10:49; d.f.=2, 16, po0:01) during the 2200– 0400 h phase. Mid-forehead temperature (Tfh ) also differed significantly between the three conditions from 1800 to 2200 h (F ¼ 15:3; d.f.=2, 16, po0:01), 2200 to 0400 h (F ¼ 41:9; d.f.=2, 16, po0:01), and 0400 to 0800 h (F ¼ 8:12; d.f.=2, 16, po0:01). Tfh changed in parallel to rectal temperature and seemed to be influenced by Ta conditions. Abdomen temperature (Tab ) was significantly the lowest in the FLR and the highest in the RHF from 2200 to 0400 h (F ¼ 23:5; d.f. =2, 16, po0:01) (see Fig. 2 and Table 2). Fig. 3 shows a comparison of extremity skin temperatures (thigh, leg, foot and hand) (left) and the temperature gradient between the skin and the Ta (right) in Constant, RHF and FLR conditions. Thigh temperatures (Tthigh ) were significantly different among the three conditions from 1800 to 2200 h (F ¼ 7:37; d.f.=2, 16, po0:01), and from 2200 to 0400 h (F ¼ 22:6; d.f.=2, 16, po0:01); Tthigh was the lowest in FLR condition, the highest in RHF and intermediate in the Constant condition. Tleg ; Tfoot and Thand showed similar patterns to Tthigh : Tthigh ; Tleg ; Tfoot and Thand did not show any difference among the conditions from 0400 to 0800 h. It should be noticed that thigh, leg, foot and hand skin temperatures became nearly identical towards 0400 h, although Ta differed greatly in the three conditions. In contrast, the temperature gradients between the skin and Ta were significantly different among the three conditions at all sites during all the three periods, the gradient between 1800 and 0800 h, being the highest in FLR, the lowest in RHF, and intermediate in the Constant condition. Fig. 4 compares the fall in Tre from 1800 to 2200 (a), 2200 to 0400 h (b) and the rise from 0400 to 0800 h (c) among the three conditions. The fall of Tre from 2200 to
Table 1 Maximum and minimum values of 24 h Tre rhythm and acrophase and nadir times among FLR, Constant and RHF conditions
FLR Constant RHF
Maximum
Acrophase
Minimum**
Nadir time**
37.3170.01 37.2770.02 37.3170.04
17:2970:02 18:2670:02 18:5370:20
36.3070.07 36.3970.04 36.6970.08
3:5170:11 4:2670:12 6:4570:09
Note: The values were obtained from the best-fitting curves applied to the raw data. po0:01:
T. Wakamura, H. Tokura / Journal of Thermal Biology 27 (2002) 439–447
443
Table 2 Results of the statistics of skin temperatures among FLR, Constant and RHF conditions Ambient temperatures
1800–2200 h Thigh Leg Foot Hand Thigh–Ta Leg–Ta Foot–Ta Hand–Ta 2200–0400 h Thigh Leg Foot Hand Thigh–Ta Leg–Ta Foot–Ta Hand–Ta 0400–0800 h Thigh Leg Foot Hand Thigh–Ta Leg–Ta Foot–Ta Hand–Ta
Time
Interaction
F
p
F
p
F
p
(d.f.=2, 16) 7.37 9.33 40.45 21.55
po0:01 po0:01 po0:01 po0:01
(d.f.=7, 56) 25.37 12.93 1.5 2.27
po0:01 po0:01 po0:3 po0:1
(d.f.=14, 98) 6.37 5.62 21.73 4.54
po0:01 po0:01 po0:01 po0:01
po0:01 po0:01 po0:01 po0:01
24.2 15.05 1.82 1.58
po0:01 po0:01 po0:2 po0:3
11.34 3.65 1.95 4.74
po0:01 po0:01 po0:05 po0:01
(d.f.=2, 16) 22.6 13 53.6 40.8
po0:01 po0:01 po0:01 po0:01
(d.f.=11, 88) 45.52 22.52 26 37.75
po0:01 po0:01 po0:01 po0:01
(d.f.=22, 176) 9.3 5.25 23.8 14.6
po0:01 po0:01 po0:01 po0:01
247.6 113.9 74.4 675.8
po0:01 po0:01 po0:01 po0:01
44.1 21.46 25.4 26
po0:01 po0:01 po0:01 po0:01
6.92 4.05 20.5 12.4
po0:01 po0:01 po0:01 po0:01
(d.f.=2, 16) 3.16 2.27 1.45 1.65
po0:1 po0:2 po0:3 po0:3
(d.f.=7, 56) 0.59 0.61 0.55 0.3
po0:7 po0:7 po0:7 po1:0
(d.f.=14, 112) 1.24 1.31 0.74 1.04
po0:4 po0:3 po0:7 po0:5
98.93 38.59 42.89 138.84
po0:01 po0:01 po0:01 po0:01
po0:7 po0:5 po0:7 po0:8
32.55 5.93 9.12 17.26
po0:01 po0:01 po0:01 po0:01
39.55 16.63 12.59 29.57
0400 h was the greatest in FLR, the lowest in RHF and intermediate in Constant conditions (F ¼ 12:9; d.f.=2, 16, po0:01). It should be noticed that the rise in Tre began before the rise in Ta in the FLR condition (Fig. 4b). Moreover, the rise in Tre from 0400 to 0800 h (c) was the highest in FLR, the lowest in RHF and intermediate in Constant conditions (F ¼ 8:49; d.f.=2, 16, po0:05).
4. Discussion What physiological mechanisms could be responsible for the finding that the core body temperature decreased considerably during the nighttime in the FLR condition? The finding could be interpreted in terms of different behaviors in the skin extremities between the FLR, Constant and RHF conditions (see Fig. 3). As seen in
0.57 0.94 0.75 0.62
Fig. 3 (right), temperature gradients between the skin and Ta (Tthigh 2Ta ; Tleg 2Ta ; Tfoot 2Ta and Thand 2Ta ) were significantly greater in the FLR condition from 1800 to 0800 h. This suggests that the heat flow from the extremities to the surroundings was the highest in this condition, resulting in the considerable decrease in the core body temperature. Teramoto et al. (1998) found that the nocturnal core body temperature further decreased considerably when Ta decreased from 271C to 25.51C over the 4 h after the participants had gone to bed and then increased from 25.51C to 271C over the next 4 h (Fall–Rise). The authors considered that the Fall–Rise condition of Ta was in accordance with the internal demand of the human body, because the setpoint of Tre fell until the middle of the night and then began to rise toward the morning — a situation that was simulated by the Fall–Rise condition in their experiments.
T. Wakamura, H. Tokura / Journal of Thermal Biology 27 (2002) 439–447
444
Sleep
36
**
**
Sleep
NS
**
**
**
12
Tthigh −T a (°C)
Tthigh (°C)
34 32 30 28 2
4
6
8
8 10 12 14 16 18 20 22 0 14
NS
**
**
6
Tleg −T a (°C)
32 30
4
**
6
8 **
10 8 6 4
28 8 10 12 14 16 18 20 22 0 36
**
2
12
34 Tleg (°C )
8
4 8 10 12 14 16 18 20 22 0
36
10
**
2
4
**
6
8 10 12 14 16 18 20 22 0
8
**
NS
2
4
**
6
8
**
12 Tfoot −Ta (°C)
Tfoot (°C)
34 32 30
10 8 6 4
28 8 10 12 14 16 18 20 22 0
2
4
6
8 10 12 14 16 18 20 22 0
8
32 30 28
4
2
4
6
8
12
34
Thand –Ta (°C)
Thand (°C)
36
2
**
**
8 10 12 14 16 18 20 22 0
Rise-High-Fall
NS
2
4
6
10 8 6 4
8
Constant
**
8 10 12 14 16 18 20 22 0
**
**
6
8
Fall-Low-Rise
Fig. 3. Distal skin temperatures (from top downwards for thigh, leg, foot, hand) in the different Ta cycles (left), and the gradient between each skin temperatures and Ta (right): mean7SEM; (–K–) Rise–High–Fall (RHF); (—) Constant; (–J–) Fall–Low–Rise (FLR) conditions (n ¼ 9).
Why did the FLR condition induce the greatest fall of Tre during the nighttime? It should be noticed that the lowering of Tre was not a passive response to Ta ; but was to be regarded as actively regulated mechanisms, because the Tre was constant with Ta of 221C between 0000 and 0200 h and started to rise before the rise of Ta
at 0400 h. The underlying physiological mechanisms might have been the lowering of set-point in Tre under the influence of the FLR condition. Skin temperatures at the extremities are highly dependent upon Ta (Aschoff, 1958). As seen in Fig. 3 (left), the skin temperatures for thigh, leg, foot and hand were almost identical between
T. Wakamura, H. Tokura / Journal of Thermal Biology 27 (2002) 439–447 (b)
(a)
445
Rise−High−Fall
0.2
-0.2
0.2
-0.4
0
Fall−Low−Rise (c)
18
20
22
0.8
** 0.6 ** *
*
-0.2 **
** -0.4
**
** ** *
0.2
** **
-0.6
**
** **
-0.8 22
0
0.4
**
** ** **
*
**
** ** 0
** ** ** **** **
-0.2
** ** ** ** **** 2
∆Tre (°C)
0.4
∆Tre (°C)
∆T re (°C)
Constant 0
4
-0.4 4
6
8
Sleep *p<0.05, **p<0.01
Fig. 4. Rectal temperature changes (DTre ) from 1800 to 0800 h, mean7SEM. (a) The fall in rectal temperature (DTre ) from 1800 to 2200 h, zero indicating the value at 1800 h. (b) The fall in rectal temperature (DTre ) from 2200 to 0400 h, zero indicating the value at 2200 h. (c) The rise in rectal temperature (DTre ) from 0400 to 0800 h, zero indicating the value at 0400 h. (–K–) Rise–High–Fall; (—) Constant; (–J–) Fall–Low–Rise conditions; po0:05; po0:01 (n ¼ 9).
0200 and 0400 h, although Ta was considerably different (281C in RHF, 251C in Constant and 221C in FLR conditions). It should be especially noted that Tthigh ; Tleg ; Tfoot and Thand in the FLR condition approached those in the Constant and RHF conditions. These findings might reflect the lowering of set-point in Tre under the influence of the FLR condition. The participants seemed to regulate their Tre at a lower value by increasing the skin temperatures at the extremities so that their actual Tre approached the reduced set-point of Tre : There is another possibility that increases in temperatures occurred due to the usage of bath towel during sleep. However, it does not seem to be the case, because, as shown in Fig. 2 (bottom), Tab was significantly the lowest in FLR, the highest in RHF and intermediate from 0000 to 0400 h (F ¼ 33; d.f.=2, 16, po0:01), although the body was covered by same bath towel, suggesting that skin temperatures may reflect physiological states within the body. Therefore, it is probable that increased skin temperatures in the FLR are not due to masking effects of the bath towel, but are actively regulated by the reduced set-point of core temperature. Humans can tolerate better a cold Ta of 151C during the daytime (LeBlanc et al., 1964, Jeong and Tokura, 1993) without any fall of Tre : However, only 31C fall of Ta from 1800 to 0400 h in the FLR condition was accompanied by ca. 11C fall of Tre : Of course, although the fall of Tre would have included a circadian
component, it was significantly greater in FLR (11C) than in the Constant (0.61C) and RHF conditions (0.31C), suggesting that the set-point of Tre has been regulated at a lower level in the FLR condition. Ta started to rise at 0400 h from 221C to 251C over a period of 4 h in the FLR condition, and began to fall from 281C to 251C in the RHF condition. As seen in Fig. 4c, rise of Tre was the greatest in FLR, the lowest in RHF and intermediate in Constant condition. As seen in Fig. 3 (right), the heat loss from the extremities, judging from (Tthigh Ta ), (Tleg Ta ), (Tfoot Ta ) and (Thand Ta ), started to decrease from 0400 to 0800 h in FLR, resulting in a sharp increase of Tre (Fig. 4c). In contrast, heat loss from the extremities started to increase from 0400 to 0800 h in the RHF condition, resulting in an inhibition of the rise in Tre (Fig. 4c). Thus, different morning time courses of Tre could be explained in terms of the different heat loss from the extremities under the influences of FLR, Constant and RHF conditions. Robinson and Fuller (1999) found that circadian rhythm of thermoregulatory systems in the squirrel monkey was greatly influenced by two kinds of Ta at 271C and 171C. The circadian rhythms of heat loss system were phase-advanced at Ta of 171C, and the nocturnal levels of Tre were significantly lower at Ta of 171C as compared to 271C. In our present experiment, similar findings were found, i.e., the circadian phase of Tre was advanced, and the nocturnal Tre was the lowest in the FLR when compared with the Constant and RHF
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conditions. This suggests that if the participants are exposed to cold at night, their circadian rhythms are phase-advanced. Tokura and Aschoff (1983) also found that the circadian rhythms of locomotor activity in the pig-tailed monkey ran faster at Ta of 171C than at 331C, supporting our present findings. According to Kr.auchi and Wirz-Justice (1994), the time course of the nocturnal decline of Tre commenced with reduced heat production and vasodilatation of the distal skin regions. When the blood flow to these skin regions increased, heat loss became greater (Kr.auchi et al., 1998). This mechanism of vasodilatation of the distal skin regions involves arteriovenous anastomoses (AVA), which are abundant in these areas and which are involved in the regulation of blood flow with sleep onset (Kr.auchi et al., 2000). After going to bed, heat loss increases significantly, sleep itself promoting this and thus enabling Tre to decrease during the night. The thermoregulatory consequences during SWS (slow wave sleep) and REM (rapid eye movement) sleep differ greatly. The decrease in Tre facilitates the appearance of SWS (Berger et al., 1988); SWS in turn promotes a further heat loss by reducing cerebral metabolism, resulting in conserving energy (McGinty and Szymusiak, 1990). Therefore, it is presumable that the FLR condition may induce sleep more deeply (via a fall in Tre ), although we did not measure the sleep electroencephalographically. According to Teramoto et al. (1998), a gradual fall of Ta during the first half of the night results in a quicker and greater fall of Tre and better subjective sleep. Thus, we conclude that a gradual decrease of room temperature in the evening and its gradual increase in the morning could accelerate the nocturnal fall of Tre and its morning rise by modifying the thermal gradient between the skin temperature in the extremities and Ta and in turn, should improve the quality of sleep.
Acknowledgements The authors thank Ms. Yumin Song and Ms. Youko Kurahashi for their assistance and data collection, and Dr. J. Waterhouse for his critical reading of the manuscript and his editorial assistance.
References Aschoff, J., 1958. Hauttemperatur und Hautdurchblutung im Dienst der Temperaturregulation. Klin. Wochenschr. 36, 193–202. Aschoff, J., 1970. Circadian rhythm of activity and body temperature. In: Hardy, J.D., Gagge, A.P., Stolwijk, J.A. (Eds.), Physiological and Behavioral Temperature Regulation. C.C. Thomas, Springfield, IL, pp. 905–919.
Aschoff, J., 1999. Masking and parametric effects of highfrequency light–dark cycles. Jpn. J. Physiol. 49, 11–18. Aschoff, J., Heise, A., 1972. Thermal conductance in man: its dependence on time of day and on ambient temperature. In: Ito, S., Ogata, K., Yoshimura, H. (Eds.), Advances in Climatic Physiology. Igaku Shoin, Tokyo, pp. 335–348. Aschoff, J., Tokura, H., 1986. Circadian activity rhythms in squirrel monkeys: entrainment by temperature cycles. J. Biol. Rhythms 1, 91–99. Berger, R.J., Palca, J.W., Walker, J.M., Phillips, N.H., 1988. Correlations between body temperature, metabolic rate and slow wave sleep in humans. Neurosci. Lett. 86, 230–234. Cabanac, M., Hildebrandt, G., Strempel, H., 1976. A study of the nyctohemeral cycle of behavioural temperature regulation in man. J. Physiol. 257, 275–291. ! J., Bolliet, V., Ravault, J.P., Chesneau, D., Ali, M.A., Falcon, Collin, J.P., 1994. Rhythmic secretion of melatonin by the superfused pike pineal organ: thermo - and photoperiod interaction. Neuroendocrinology 60, 535–543. Firth, B.T., Belan, I., Kennaway, D.J., Moyer, R.W., 1999. Thermocyclic entrainment of lizard blood plasma melatonin rhythms in constant and cyclic photic environments. Am. J. Physiol. 277 (Regulatory Integrative Comp. Physiol. 46), R1620–R1626. Jeong, W.S., Tokura, H., 1993. Different thermal conditions of the extremities affect thermoregulation in clothed man. Eur. J. Appl. Physiol. Occup. Physiol. 67, 481–485. Kr.auchi, K., Wirz-Justice, A., 1994. Circadian rhythm of heat production, heat rate, and skin and core temperature under unmasking conditions in men. Am. J. Physiol. 267 (Regulatory Integrative Comp. Physiol. 36), R819–R829. Kr.auchi, K., Cajochen, C., Wirz-Justice, A., 1998. Circadian and homeostatic regulation of core body temperature and alertness in humans: what is the role of melatonin? In: Honma, K., Honma, S. (Eds.), Circadian Clocks and Entrainment. Hokkaido University Press, Sapporo, pp. 131–145. Kr.auchi, K., Cajochen, C., Werth, E., Wirz-Justice, A., 2000. Functional link between distal vasodilation and sleep-onset latency? Am. J. Physiol. Regulatory Integrative Comp. Physiol. 278, R741–R748. LeBlanc, J., Pouliot, M., Rheaume, S., 1964. Thermal balance and biogenic amine excretion in Gasp!e fisherman exposed to cold. J. Appl. Physiol. 19, 9–12. Liu, Y., Merrow, M., Loros, J.J., Dunlap, J.C., 1998. How temperature changes reset a circadian oscillator. Science 281, 825–829. McGinty, D., Szymusiak, R., 1990. Keeping cool: a hypothesis about the mechanisms and functions of slow-wave sleep. Trends Neurosci. 13, 480–487. Park, S.J., Tokura, H., 1997. Effects of two types of clothing on the day–night variation of core temperature and salivary immunoglobulin A. Chronobiol. Int. 14, 607–617. Rawson, K.S., 1960. Effects of tissue temperature on mammalian activity rhythms. Cold Spring Harbor Symp. Quant. Biol. 25, 105–113. Rensing, L., Kallies, A., Gebauer, G., Mohsenzadeh, S., 1995. The effects of temperature change on the circadian clock of Neurospora. In: Chadwick, D.J. (Ed.), Circadian Clocks and their Adjustment. Wiley, Chichester, pp. 26–41.
T. Wakamura, H. Tokura / Journal of Thermal Biology 27 (2002) 439–447 Robinson, E.L., Fuller, C.A., 1999. Endogenous thermoregulatory rhythms of squirrel monkeys in thermoneutrality and cold. Am. J. Physiol. 276 (Regulatory Integrative Comp. Physiol. 45), R1397–R4107. Rusak, B., Zucker, I., 1979. Neural regulation of circadian rhythms. Physiol. Rev. 59, 449–526. Sweeney, B.M., Hastings, J.W., 1960. Effects of temperature upon diurnal rhythms. Cold Spring Harbor Symp. Quant. Biol. 25, 87–103. Teramoto, Y., Tokura, H., Ioki, I., Suho, S., Inoshiri, R., Masuda, M., 1998. The effect of room temperature on rectal temperature during night sleep. J. Thermal Biol. 23, 15–22.
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Tokura, H., Aschoff, J., 1983. Effects of temperature on the circadian rhythm of pig-tailed macaques Mocaca nemestrina. Am. J. Physiol. 245 (Regulatory Integrative Comp. Physiol. 14), R800–R804. Underwood, H., 1985. Pineal melatonin rhythms in the lizards Anolis carolinensis: effects of light and temperature cycles. J. Comp. Physiol. A 157, 57–65. Wever R. A., 1979. The circadian system of man. Results of Experiments under Temporal Isolation. Springer-Verlag, New York, pp. 93–94.
Circadian rhythm of rectal temperature in humans under different ambient temperature cycles Tomoko Wakamura*,1, Hiromi Tokura2 Department of Environmental Health, Nara Women’s University, Nara 630-8506, Japan Received 27 July 2001; accepted 29 January 2002
Abstract 1. The present study is aimed at knowing whether ambient temperature (Ta ) cycles exert any influence on circadian rhythm of rectal temperature (Tre ) in humans. 2. Three different Ta conditions were provided: (1) Ta was kept constant at 251C for 24 h (Constant). (2) Ta decreased from 251C to 221C over 4 h from 1800 to 2200 h, was then kept constant at 221C for additional 6 h and increased to 251C over 4 h from 0400 to 0800 h (FLR). (3) Ta was changed reversibly from 251C through 281C to 251C with identical time schedule like FLR (RHF). 3. Minimum level and evening decreasing rate/morning increasing rate in Tre were significantly the lowest and greatest in FLR. r 2002 Elsevier Science Ltd. All rights reserved. Keywords: Humans; Circadian rhythm; Rectal temperature; Skin temperatures; Ambient temperature cycle
1. Introduction Light and ambient temperature (Ta ) play an important role as Zeitgeber for circadian rhythm from unicellular organisms to higher animals (see Rusak and Zucker, 1979; Rensing et al., 1995). Thermoregulation in ectotherms (poikilotherms) such as reptiles depends on Ta (Firth et al., 1999) and their circadian rhythms of locomotor and pineal gland activities are entrained by the Ta cycles (Underwood, 1985). On the other hand, thermoregulation in endotherms (homeotherms) maintains steady-state conditions by balancing metabolic heat production and heat loss (Aschoff, 1958), their internal regulation of body temperature being more *Corresponding author. Fax: +81-78-925-0878. E-mail address: tomoko [email protected] (T. Wakamura). 1 Present address: College of Nursing Art & Science, Hyogo, Akashi 673-8588, Japan. 2 Present address: Dept. of Working Physiology and Ergonomics, Nofer Institute of Occupational Medicine, Łodz, Poland.
autonomous than that of poikilotherms. It is widely reported that there are temperature compensation mechanisms for the function of circadian pacemakers (Sweeney and Hastings, 1960), and the temperature coefficient (Q10) is closer to 1.0 in humans (Rawson, 1960). Even though, in some primates, circadian locomotor rhythms have been entrained by the Ta cycles (Tokura and Aschoff, 1983; Aschoff and Tokura, 1986), such cycles have been considered less effective as Zeitgeber than the light–dark cycles (Aschoff, 1999). This result also accords with the observation that, although the photoperiod and Ta cycles act together to entrain the circadian rhythm of melatonin secretion in fish, the temperature cycles were less effective than the ! et al., 1994). photoperiod (Falcon However, recently, Liu et al. (1998) found that Ta was a more effective entraining agent than light in Neurospora. Also, Robinson and Fuller (1999) demonstrated that the free-running circadian period (t) of the squirrel monkeys was shorter when they were studied in mild cold conditions rather than in the thermoneutral zone. Just as light–dark cycles exist in natural condition, so also do the Ta cycles; that is, the Ta at midday is higher
0306-4565/02/$ - see front matter r 2002 Elsevier Science Ltd. All rights reserved. PII: S 0 3 0 6 - 4 5 6 5 ( 0 2 ) 0 0 0 1 4 - 1
440
T. Wakamura, H. Tokura / Journal of Thermal Biology 27 (2002) 439–447
than that at midnight (solar time). In humans, Aschoff and Heise (1972) showed that the range of oscillation in rectal temperature depended on Ta (ranging from 201C to 321C). In addition, Wever (1979) demonstrated in humans that t; measured under conditions when Ta was self-controlled, was significantly longer than when it was measured under conditions of a constant Ta (24.91C). Most studies do not seem to have considered the possible influence of the day–night variation of Ta within the thermoneutral zone. Teramoto et al. (1998) have found that temperature cycles have profound influence upon the behaviors of core body temperature during night sleep. They found that a gradual decrease in room temperature from 271C to 25.51C over the 4 h from midnight to 0400 h, and then a gradual increase from 25.51C to 271C over the 4 h from 0400 to 0800 h (Fall–Rise) caused a further decrease in core body temperature, and was accompanied by the feeling of a better sleep, when compared with opposite changes of room temperature (Rise–Fall). The authors considered that these findings indicated that changes in room temperature affected the circadian variation in the set-point of core body temperature, and that they could induce a deeper nocturnal fall of core body temperature. However, if this hypothesis is true, it is essential to measure the core body temperature over 24-h period under the influence of Ta cycles that mimic the circadian change of set-point in core temperature, because this setpoint varies in a circadian manner (Aschoff, 1970; Cabanac et al., 1976). Bearing these considerations in mind, our present experiment has been aimed at investigating how the circadian rhythm of core body temperature could be influenced by changes within the thermoneutral zone of the Ta cycle.
2. Methods 2.1. Participants Nine female students were screened in terms of general medical and psychological health. Their physical characteristics were as follows: age, 21.871.8 (SD) yr (range 19–24); height, 1.6070.04 (SD) m (range 1.54– 1.66); weight, 53.778.6 (SD) kg (range 44–68); body mass index, 21.0072.67 (SD) kg/m2 (range 17.18–24.24) (BMI; weight/height2); and body surface area, 1.5070.12 (SD) m2 (range 1.38–1.69) [calculated, with weight in kg and height in cm, as weight0.444 height0.663 88.83 cm/kg]. They had no self-reported sleep disorders and none were smokers. At the time of the study, they were in the follicular phase of their regular menstrual cycle as indicated by their basal body temperature.
The Ethic and Research Committee of Nara Women’s University approved the experimental protocol. The nature, purpose, and risks of the study were explained before participants gave their written consent. They were permitted to stop the experiment at any time whenever they wished to do so; however, all the participants completed the study without complaint.
2.2. Experimental protocol The experiments were carried out between May and July 2000. Participants were instructed to adhere to their regular sleep schedules (sleep between 0000 h730 min and 0800 h730 min) before the experiment. They were required to refrain from heavy physical activity during the day before entering the experimental chamber. The participants entered the experimental chamber at 1000 h. The room was controlled for temperature, humidity (60% RH) and light, and was isolated from external sound and light. They stayed in the room for 3 days (see Fig. 1 for the experimental protocol). The Ta during the first daytime, the day of entry, was kept constant at 251C (Constant). During the subsequent nights, the Ta between 2200 and 0400 h was set randomly to 2270.21C or 2870.61C. In the 221C condition, the temperature was lowered to this value from the control value of 251C at 1800 h, and was raised back to this control value at 0400 h (see Fig. 1), mimicking the natural nocturnal fall and rise of Ta : This was called Fall–Low–Rise (FLR) condition. When the temperature was raised to 281C, the time course of the changes was similar; this was called the Rise–High– Fall (RHF) condition. The changes in room temperature, with the exception of the first (control) day, were counterbalanced. Lighting was controlled to mimic the natural light condition. Participants were exposed to 5000 lx from 0800 to 1500 h and 200 lx from 1800 to 0000 h. Time of lights-off and retiring to bed were standardized throughout, time in bed being from 0000 to 0800 h. In addition, from 1900 h (after their meal) to 0000 h, participants were required to adopt a semi-Fowler’s position in order to minimize the differences of heat loss due to physiological posture changes, their head elevated to about 451 angle, using a reclining chair. The experiment commenced with the application of the rectal and skin temperature probes. Meals were provided at 0830, 1200 and 1800 h; total calorie intake was 7531 kJ/day, a value calculated to balance daily energy expenditure. These meals had the same composition for all the participants. Water was available at any time. Reading, writing, and talking (although none of these were permitted to be overstimulating) were allowed during the experiment.
T. Wakamura, H. Tokura / Journal of Thermal Biology 27 (2002) 439–447
441
Rise-High-Fall
Ambient Temperature Cycle (°C)
Sleep
6,000
Fall-Low-Rise
5,000 28 4,000 25
3,000 2,000
22
Light Intensity Cycle (lx)
Constant
31
1,000 19
0 8
10
12
14
16
18
20
22
0
2
4
6
8
Meal Fig. 1. Experimental schedule: (–K–) Rise–High–Fall (RHF); (—) Constant; (–J–) Fall–Low–Rise (FLR) conditions during a day. Light intensity: light gray color (right vertical axis). Meal times: 0830, 1200 and 1800 h. On the first day, the condition selected was Constant. On the subsequent days, the conditions were RHF or FLR in a counter-balanced design.
The clothing worn was a short-sleeved shirt and kneelength pants made of 100% cotton, and no socks; this was chosen according to Park and Tokura (1997). At night, the same clothing was worn and with the addition of bath towel. 2.3. Data acquisition Temperatures (rectal and skin) were continuously recorded by a logger (LT-8A, Gram, Japan), every 1 min and were averaged later, every 30 min. Rectal temperature (Tre ) as a measure of core body temperature was recorded by a thermistor probe (LT-ST08-11, accuracy70.011C; Gram, Japan) inserted 10 cm past the anal sphincter. Skin temperatures were also recorded by thermistor probes (LT-ST08-12, accuracy70.011C; Gram, Japan) fixed to the skin with thin, air-permeable adhesive surgical tape (Surgical tape, Nichban, Japan). Skin temperatures were measured at eight sites as follows: mid-forehead (Tfh ), abdomen, (Tab ), left and right (later averaged) centers of the back of the hand (Thand ), middle, left and right (later averaged) centers of the instep of the foot (Tfoot ), left leg (Tleg ) and mid-thigh on the rectus femoris muscle (Tthigh ). 2.4. Data analysis Raw data of temperatures were inspected visually and segments that had been lost (due to slippage of the temperature sensor) were estimated by interpolation. Raw data from each participant were averaged over 30 min. Maximum and minimum values of rectal temperatures and the time when those occurred were
individually derived from cosine curve analysis of the raw data, and their average values were compared. Differences over time between the three Ta conditions were analyzed by using a two-way analysis of variance (ANOVA) with repeated measures. Interactions (condition time) were also assessed. The ANOVA was applied separately for three periods: 1800– 2200, 2200– 0400, and 0400–0800 h. Huynh–Feldt (H–F) statistics were used to adjust the covariance matrix for violations of sphericity (Mauchly). Though p values of H–F were based on corrected degrees of freedom, the original degrees of freedom were used. When the F ratio proved significant, Tukey’s and Dunnett’s multiple post hoc tests were applied to locate a significant difference between the means. The maximum and minimum values, their timing, and their differences were extracted from this analysis. Data were expressed usually as means7SEM. po0:05 was used to define significance.
3. Results Fig. 2 shows a comparison of 24 h rhythms in: upper, rectal temperature (Tre ); middle, mid-forehead skin temperature (Tfh ) and bottom, abdomen skin temperature (Tab ) among Constant, RHF and FLR conditions. Average maximum and minimum values of Tre were obtained from individual cosine curves fitted to the raw data. The average maximum Tre values were 37.2770.021C (mean7SD), 37.3170.011C and 37.3170.041C in Constant, FLR and RHF conditions. These were not significantly different (Table 1). The
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442
Sleep
Tre
NS
**
37.6 37.4 37.2 37 36.8 36.6 36.4 36.2 36 35.8 35.6 35.4 8
Tfh
NS
10
12
14
16
18
20
22
0
**
36 35.5 35 34.5 34 33.5 33 32.5 32 31.5 31 8
10
12
14
16
18
20
4
**
22
0
NS
36.5
2
6
8
**
2
4
6
8
NS
**
36
Tab
35.5 35 34.5
Rise-High-Fall Constant Fall-Low-Rise
34
**
33.5 8
10 12 14 16 18 20 22
0
2
4
6
8
Fig. 2. Rectal (upper), mid-forehead (middle) and abdomen (lower) temperatures (mean7SEM) during the three different Ta cycles: sleep time (0000–0800 h) indicated by arrows; (–K–) Rise–High–Fall (RHF); (—) Constant; (–J–) Fall–Low–Rise (FLR) conditions; po0:01 (n ¼ 9).
average minimum Tre values were 36.3970.041C, 36.3070.071C and 36.6970.081C in Constant, FLR and RHF conditions (Table 1), which were significantly different among the three conditions (F ¼ 10:7; d.f.=2, 16, po0:01). Minimum Tre was not significantly different between FLR and Constant conditions
(p ¼ 0:57), but was significantly different (po0:01) between RHF and FLR and was also significantly different (po0:01) between RHF and Constant conditions. The nadir times of Tre were 0046 h712 min, 0351 h711 min and 0645 h79 min in Constant, FLR and RHF conditions, respectively, which were significantly different among the three conditions (F ¼ 12:1; d.f.=2, 16, po0:01). Whereas Tre did not differ from 1800 to 2200 h among three conditions, Tre was the lowest in the FLR condition and the highest in the RHF condition (F ¼ 10:49; d.f.=2, 16, po0:01) during the 2200– 0400 h phase. Mid-forehead temperature (Tfh ) also differed significantly between the three conditions from 1800 to 2200 h (F ¼ 15:3; d.f.=2, 16, po0:01), 2200 to 0400 h (F ¼ 41:9; d.f.=2, 16, po0:01), and 0400 to 0800 h (F ¼ 8:12; d.f.=2, 16, po0:01). Tfh changed in parallel to rectal temperature and seemed to be influenced by Ta conditions. Abdomen temperature (Tab ) was significantly the lowest in the FLR and the highest in the RHF from 2200 to 0400 h (F ¼ 23:5; d.f. =2, 16, po0:01) (see Fig. 2 and Table 2). Fig. 3 shows a comparison of extremity skin temperatures (thigh, leg, foot and hand) (left) and the temperature gradient between the skin and the Ta (right) in Constant, RHF and FLR conditions. Thigh temperatures (Tthigh ) were significantly different among the three conditions from 1800 to 2200 h (F ¼ 7:37; d.f.=2, 16, po0:01), and from 2200 to 0400 h (F ¼ 22:6; d.f.=2, 16, po0:01); Tthigh was the lowest in FLR condition, the highest in RHF and intermediate in the Constant condition. Tleg ; Tfoot and Thand showed similar patterns to Tthigh : Tthigh ; Tleg ; Tfoot and Thand did not show any difference among the conditions from 0400 to 0800 h. It should be noticed that thigh, leg, foot and hand skin temperatures became nearly identical towards 0400 h, although Ta differed greatly in the three conditions. In contrast, the temperature gradients between the skin and Ta were significantly different among the three conditions at all sites during all the three periods, the gradient between 1800 and 0800 h, being the highest in FLR, the lowest in RHF, and intermediate in the Constant condition. Fig. 4 compares the fall in Tre from 1800 to 2200 (a), 2200 to 0400 h (b) and the rise from 0400 to 0800 h (c) among the three conditions. The fall of Tre from 2200 to
Table 1 Maximum and minimum values of 24 h Tre rhythm and acrophase and nadir times among FLR, Constant and RHF conditions
FLR Constant RHF
Maximum
Acrophase
Minimum**
Nadir time**
37.3170.01 37.2770.02 37.3170.04
17:2970:02 18:2670:02 18:5370:20
36.3070.07 36.3970.04 36.6970.08
3:5170:11 4:2670:12 6:4570:09
Note: The values were obtained from the best-fitting curves applied to the raw data. po0:01:
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443
Table 2 Results of the statistics of skin temperatures among FLR, Constant and RHF conditions Ambient temperatures
1800–2200 h Thigh Leg Foot Hand Thigh–Ta Leg–Ta Foot–Ta Hand–Ta 2200–0400 h Thigh Leg Foot Hand Thigh–Ta Leg–Ta Foot–Ta Hand–Ta 0400–0800 h Thigh Leg Foot Hand Thigh–Ta Leg–Ta Foot–Ta Hand–Ta
Time
Interaction
F
p
F
p
F
p
(d.f.=2, 16) 7.37 9.33 40.45 21.55
po0:01 po0:01 po0:01 po0:01
(d.f.=7, 56) 25.37 12.93 1.5 2.27
po0:01 po0:01 po0:3 po0:1
(d.f.=14, 98) 6.37 5.62 21.73 4.54
po0:01 po0:01 po0:01 po0:01
po0:01 po0:01 po0:01 po0:01
24.2 15.05 1.82 1.58
po0:01 po0:01 po0:2 po0:3
11.34 3.65 1.95 4.74
po0:01 po0:01 po0:05 po0:01
(d.f.=2, 16) 22.6 13 53.6 40.8
po0:01 po0:01 po0:01 po0:01
(d.f.=11, 88) 45.52 22.52 26 37.75
po0:01 po0:01 po0:01 po0:01
(d.f.=22, 176) 9.3 5.25 23.8 14.6
po0:01 po0:01 po0:01 po0:01
247.6 113.9 74.4 675.8
po0:01 po0:01 po0:01 po0:01
44.1 21.46 25.4 26
po0:01 po0:01 po0:01 po0:01
6.92 4.05 20.5 12.4
po0:01 po0:01 po0:01 po0:01
(d.f.=2, 16) 3.16 2.27 1.45 1.65
po0:1 po0:2 po0:3 po0:3
(d.f.=7, 56) 0.59 0.61 0.55 0.3
po0:7 po0:7 po0:7 po1:0
(d.f.=14, 112) 1.24 1.31 0.74 1.04
po0:4 po0:3 po0:7 po0:5
98.93 38.59 42.89 138.84
po0:01 po0:01 po0:01 po0:01
po0:7 po0:5 po0:7 po0:8
32.55 5.93 9.12 17.26
po0:01 po0:01 po0:01 po0:01
39.55 16.63 12.59 29.57
0400 h was the greatest in FLR, the lowest in RHF and intermediate in Constant conditions (F ¼ 12:9; d.f.=2, 16, po0:01). It should be noticed that the rise in Tre began before the rise in Ta in the FLR condition (Fig. 4b). Moreover, the rise in Tre from 0400 to 0800 h (c) was the highest in FLR, the lowest in RHF and intermediate in Constant conditions (F ¼ 8:49; d.f.=2, 16, po0:05).
4. Discussion What physiological mechanisms could be responsible for the finding that the core body temperature decreased considerably during the nighttime in the FLR condition? The finding could be interpreted in terms of different behaviors in the skin extremities between the FLR, Constant and RHF conditions (see Fig. 3). As seen in
0.57 0.94 0.75 0.62
Fig. 3 (right), temperature gradients between the skin and Ta (Tthigh 2Ta ; Tleg 2Ta ; Tfoot 2Ta and Thand 2Ta ) were significantly greater in the FLR condition from 1800 to 0800 h. This suggests that the heat flow from the extremities to the surroundings was the highest in this condition, resulting in the considerable decrease in the core body temperature. Teramoto et al. (1998) found that the nocturnal core body temperature further decreased considerably when Ta decreased from 271C to 25.51C over the 4 h after the participants had gone to bed and then increased from 25.51C to 271C over the next 4 h (Fall–Rise). The authors considered that the Fall–Rise condition of Ta was in accordance with the internal demand of the human body, because the setpoint of Tre fell until the middle of the night and then began to rise toward the morning — a situation that was simulated by the Fall–Rise condition in their experiments.
T. Wakamura, H. Tokura / Journal of Thermal Biology 27 (2002) 439–447
444
Sleep
36
**
**
Sleep
NS
**
**
**
12
Tthigh −T a (°C)
Tthigh (°C)
34 32 30 28 2
4
6
8
8 10 12 14 16 18 20 22 0 14
NS
**
**
6
Tleg −T a (°C)
32 30
4
**
6
8 **
10 8 6 4
28 8 10 12 14 16 18 20 22 0 36
**
2
12
34 Tleg (°C )
8
4 8 10 12 14 16 18 20 22 0
36
10
**
2
4
**
6
8 10 12 14 16 18 20 22 0
8
**
NS
2
4
**
6
8
**
12 Tfoot −Ta (°C)
Tfoot (°C)
34 32 30
10 8 6 4
28 8 10 12 14 16 18 20 22 0
2
4
6
8 10 12 14 16 18 20 22 0
8
32 30 28
4
2
4
6
8
12
34
Thand –Ta (°C)
Thand (°C)
36
2
**
**
8 10 12 14 16 18 20 22 0
Rise-High-Fall
NS
2
4
6
10 8 6 4
8
Constant
**
8 10 12 14 16 18 20 22 0
**
**
6
8
Fall-Low-Rise
Fig. 3. Distal skin temperatures (from top downwards for thigh, leg, foot, hand) in the different Ta cycles (left), and the gradient between each skin temperatures and Ta (right): mean7SEM; (–K–) Rise–High–Fall (RHF); (—) Constant; (–J–) Fall–Low–Rise (FLR) conditions (n ¼ 9).
Why did the FLR condition induce the greatest fall of Tre during the nighttime? It should be noticed that the lowering of Tre was not a passive response to Ta ; but was to be regarded as actively regulated mechanisms, because the Tre was constant with Ta of 221C between 0000 and 0200 h and started to rise before the rise of Ta
at 0400 h. The underlying physiological mechanisms might have been the lowering of set-point in Tre under the influence of the FLR condition. Skin temperatures at the extremities are highly dependent upon Ta (Aschoff, 1958). As seen in Fig. 3 (left), the skin temperatures for thigh, leg, foot and hand were almost identical between
T. Wakamura, H. Tokura / Journal of Thermal Biology 27 (2002) 439–447 (b)
(a)
445
Rise−High−Fall
0.2
-0.2
0.2
-0.4
0
Fall−Low−Rise (c)
18
20
22
0.8
** 0.6 ** *
*
-0.2 **
** -0.4
**
** ** *
0.2
** **
-0.6
**
** **
-0.8 22
0
0.4
**
** ** **
*
**
** ** 0
** ** ** **** **
-0.2
** ** ** ** **** 2
∆Tre (°C)
0.4
∆Tre (°C)
∆T re (°C)
Constant 0
4
-0.4 4
6
8
Sleep *p<0.05, **p<0.01
Fig. 4. Rectal temperature changes (DTre ) from 1800 to 0800 h, mean7SEM. (a) The fall in rectal temperature (DTre ) from 1800 to 2200 h, zero indicating the value at 1800 h. (b) The fall in rectal temperature (DTre ) from 2200 to 0400 h, zero indicating the value at 2200 h. (c) The rise in rectal temperature (DTre ) from 0400 to 0800 h, zero indicating the value at 0400 h. (–K–) Rise–High–Fall; (—) Constant; (–J–) Fall–Low–Rise conditions; po0:05; po0:01 (n ¼ 9).
0200 and 0400 h, although Ta was considerably different (281C in RHF, 251C in Constant and 221C in FLR conditions). It should be especially noted that Tthigh ; Tleg ; Tfoot and Thand in the FLR condition approached those in the Constant and RHF conditions. These findings might reflect the lowering of set-point in Tre under the influence of the FLR condition. The participants seemed to regulate their Tre at a lower value by increasing the skin temperatures at the extremities so that their actual Tre approached the reduced set-point of Tre : There is another possibility that increases in temperatures occurred due to the usage of bath towel during sleep. However, it does not seem to be the case, because, as shown in Fig. 2 (bottom), Tab was significantly the lowest in FLR, the highest in RHF and intermediate from 0000 to 0400 h (F ¼ 33; d.f.=2, 16, po0:01), although the body was covered by same bath towel, suggesting that skin temperatures may reflect physiological states within the body. Therefore, it is probable that increased skin temperatures in the FLR are not due to masking effects of the bath towel, but are actively regulated by the reduced set-point of core temperature. Humans can tolerate better a cold Ta of 151C during the daytime (LeBlanc et al., 1964, Jeong and Tokura, 1993) without any fall of Tre : However, only 31C fall of Ta from 1800 to 0400 h in the FLR condition was accompanied by ca. 11C fall of Tre : Of course, although the fall of Tre would have included a circadian
component, it was significantly greater in FLR (11C) than in the Constant (0.61C) and RHF conditions (0.31C), suggesting that the set-point of Tre has been regulated at a lower level in the FLR condition. Ta started to rise at 0400 h from 221C to 251C over a period of 4 h in the FLR condition, and began to fall from 281C to 251C in the RHF condition. As seen in Fig. 4c, rise of Tre was the greatest in FLR, the lowest in RHF and intermediate in Constant condition. As seen in Fig. 3 (right), the heat loss from the extremities, judging from (Tthigh Ta ), (Tleg Ta ), (Tfoot Ta ) and (Thand Ta ), started to decrease from 0400 to 0800 h in FLR, resulting in a sharp increase of Tre (Fig. 4c). In contrast, heat loss from the extremities started to increase from 0400 to 0800 h in the RHF condition, resulting in an inhibition of the rise in Tre (Fig. 4c). Thus, different morning time courses of Tre could be explained in terms of the different heat loss from the extremities under the influences of FLR, Constant and RHF conditions. Robinson and Fuller (1999) found that circadian rhythm of thermoregulatory systems in the squirrel monkey was greatly influenced by two kinds of Ta at 271C and 171C. The circadian rhythms of heat loss system were phase-advanced at Ta of 171C, and the nocturnal levels of Tre were significantly lower at Ta of 171C as compared to 271C. In our present experiment, similar findings were found, i.e., the circadian phase of Tre was advanced, and the nocturnal Tre was the lowest in the FLR when compared with the Constant and RHF
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conditions. This suggests that if the participants are exposed to cold at night, their circadian rhythms are phase-advanced. Tokura and Aschoff (1983) also found that the circadian rhythms of locomotor activity in the pig-tailed monkey ran faster at Ta of 171C than at 331C, supporting our present findings. According to Kr.auchi and Wirz-Justice (1994), the time course of the nocturnal decline of Tre commenced with reduced heat production and vasodilatation of the distal skin regions. When the blood flow to these skin regions increased, heat loss became greater (Kr.auchi et al., 1998). This mechanism of vasodilatation of the distal skin regions involves arteriovenous anastomoses (AVA), which are abundant in these areas and which are involved in the regulation of blood flow with sleep onset (Kr.auchi et al., 2000). After going to bed, heat loss increases significantly, sleep itself promoting this and thus enabling Tre to decrease during the night. The thermoregulatory consequences during SWS (slow wave sleep) and REM (rapid eye movement) sleep differ greatly. The decrease in Tre facilitates the appearance of SWS (Berger et al., 1988); SWS in turn promotes a further heat loss by reducing cerebral metabolism, resulting in conserving energy (McGinty and Szymusiak, 1990). Therefore, it is presumable that the FLR condition may induce sleep more deeply (via a fall in Tre ), although we did not measure the sleep electroencephalographically. According to Teramoto et al. (1998), a gradual fall of Ta during the first half of the night results in a quicker and greater fall of Tre and better subjective sleep. Thus, we conclude that a gradual decrease of room temperature in the evening and its gradual increase in the morning could accelerate the nocturnal fall of Tre and its morning rise by modifying the thermal gradient between the skin temperature in the extremities and Ta and in turn, should improve the quality of sleep.
Acknowledgements The authors thank Ms. Yumin Song and Ms. Youko Kurahashi for their assistance and data collection, and Dr. J. Waterhouse for his critical reading of the manuscript and his editorial assistance.
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