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Differential heating of trunk and extremities. Effects on thermoregulation mechanisms.

Experiments in which the whole human body was heated or cooled are compared with others in which one extremity (arm or leg) was simultaneously cooled or heated. With a warm load on the rest of the body resulting in general sweating, a cold load on one extremity did not evoke local shivering; with general body cooling, heating one limb did not stop the shivering. Skin temperatures of the other parts of the body were not influenced by warming or cooling one extremity. Evaporative heat loss was influenced by local, mean skin and core temperature, whereas shivering did not depend on local temperature, and vasomotor control seemed to be controlled predominantly by central temperatures. A cold load on an extremity during whole body heating in most cases induced an oscillatory behaviour of core temperature and of the evaporative heat loss from the body and the extremity. It is assumed that local, mean skin and core temperatures influence the three autonomous effector systems to very different degree.

Biomechanical Phenomena↗

Diurnal changes of thermoregulatory functions in pigeons. I. Effector mechanisms.

In pigeons, we studied the diurnal variation of body temperatures and its dependence on the diurnal variations of shivering, vasomotor activity and panting in light-dark (LSD) - conditions (12:12 h, 100:1 Lux) and in different, but for at least 24 h constant ambient temperatures. In low ambient temperatures (below thermoneutrality) shivering was reduced shortly after lights off (early dark phase), and it increased again some hours before lights on (late dark phase); the lower the ambient temperature, the larger the reduction of shivering and the shorter the time of reduction. Within thermoneutrality, the decrease of Tb in the early dark phase was associated with an increase of foot skin temperature, probably due to vasodilatation. Later-on foot skin temperature decreased again (vasoconstriction). The feet remained constricted even in the late dark phase, when Tb already increased. At higher ambient temperature (above thermoneutrality) vasodilatation persisted all over the 24 h, while in these conditions respiratory rate increased significantly after lights off. The described diurnal variations of thermoregulatory effector mechanisms are in agreement with the concept of an active adjustment of the body temperature rhythm.

Animals↗

EMG activity in pectoral and femoral muscles during spinal cord cooling in exercising pigeons.

Adult domestic pigeons, with thermodes chronically implanted in the vertebral canal, were trained to walk on a treadmill. In the first series of experiments, EMG activity in a pectoral (M. pectoralis) and a femoral muscle (M. biceps femoris) was measured to determine if shivering could occur during exercise. When the spinal cord was cooled (36.2 +/- 0.5 degrees C) during exercise (0.6 km/h), pectoral muscle EMG activity increased by 80%, while femoral muscle EMG activity did not change significantly. EMG activity remained unchanged during exercise in control experiments where the spinal cord was not cooled. In the second series of experiments, the spinal cord was first cooled (36.1 +/- 0.5 degrees C) for 5 min in resting pigeons and then the treadmill was started. Spinal cord cooling during rest significantly increased pectoral muscle EMG activity but not that of the femoral muscle. Within 1 s after the onset of exercise, EMG activity in the pectoral muscle decreased by 74%. In both series of experiments, shivering was not induced in the femoral muscle. The level of pectoral muscle EMG activity stimulated by spinal cord cooling during exercise in the first series of experiments corresponded to the level to which EMG activity was reduced by exercise during spinal cord cooling in the second series of experiments (192% and 186% in relation to the post-cooling level, respectively). It is concluded that shivering can be induced in the pectoral muscle by spinal cord cooling during exercise in the pigeon.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Temperatures of skin, subcutaneous tissue, muscle and core in resting men in cold, comfortable and hot conditions.

To examine the core-shell model of temperature distribution and the possible role of subcutaneous temperature in heat regulation, comprehensive temperature measurements were made on six nude resting men exposed for 2-3 h to comfort (27 degrees C), cold (15 degrees C) and heat (45 degrees C). Cold produced strong shivering and heat caused heavy sweating. Temperatures were recorded every 10 min from: esophagus, rectum and auditory canal; back muscle and thigh muscle at 20 mm and 40 mm depths; 6 subcutaneous sites; and 16 skin sites. Average temperatures at these 29 sites were tabulated at the ends of comfort, hot and cold and the onsets of sweating and shivering. Body temperature changes were slow to develop, the skin temperatures being fastest, and successively deeper tissues progressively slower. There was occasional after-drop and after-rise. The data were consistent with the core-shell concept. The temperature gradient from subcutaneous tissue to skin, which differed substantially with comfort, the onset of shivering and the onset of sweating, could serve as a regulatory signal. The data are now in computer format and may be of interest to biothermal modelers.

Adult↗

Effects of repeated short-term cold exposures on cold induced thermogenesis of women.

The effects of repeated exposures to resting cold air (10 degrees C) on the shivering and thermogenic responses of women to standard cold stress were investigated. Ten women, aged 18 to 34 years, were divided into two groups of five women each. One group, the acclimated (A) was exposed ten times within 2 weeks, the first and the last exposures being the pre- and post-tests, respectively. The second group, the control (C) was exposed twice within 18 days. Measurements of rectal and skin temperatures, oxygen uptake, time to onset of shivering (TOS), and perceived cold were performed during all exposures. Shivering responses were evaluated by electromyography and visually. A significant (P less than 0.05) increase was seen in TOS (from 26.2 min to 55.6 min), and a significant decrease was seen in thermoregulatory heat production (from 14.78 kcal/h to -2.64 kcal/h) in group A; these changes were evident after about five exposures. It is concluded that the women became cold acclimated as a result of the repeated short-term resting cold air exposures.

Acclimatization↗

Cold-adaptive modifications in man induced by repeated short-term cold-exposures and during a 10-day and-night cold-exposure.

Two types of cold exposures were carried out in humans. A. Fourteen subjects were exposed 4-7 times within 2 weeks to the following conditions: ambient temperature was decreased from 28 degrees C to between plus and minus 5 degrees C; the subjects wore a bathing suit and remained in a resting position during the exposure which lasted for 1h. B. Nine conscripts were studied before and after a 10-day exercise, during which they were exposed to moderately cold conditions during day and night. The exercise did not require increased physical activity. In two thirds of the subjects A, metabolic reactions and shivering threshold were shifted to a lower weighted mean body temperature as well as a lower esophageal temperature ("hypothermic" type of adaptation). This modification in the thermoregulatory system was linked with a reduction in thermal discomfort and cold sensation. No change was found in the resting metabolic rate nor was there any indication of the development of non-shivering thermogenesis. Similar modifications were found in 4 of the 9 soldiers (study B). These 4, however, had particularly high shivering thresholds before the 10-day exercise and the values found thereafter were no lower than those found in the remaining five and in the subjects of group A before the cold-exposure regimen.

Acclimatization↗

Cold thermoregulatory changes induced by sleep deprivation in men.

The aim of this study was to evaluate the thermoregulatory changes induced by 27-h of sleep deprivation (SD) in men at rest both in a comfortable ambient temperature and in cold air. A group of 12 male subjects were placed in a comfortable ambient temperature (dry bulb temperature, Tdb = 25 degrees C, relative humidity, rh = 40%-50%, clothing insulation = 1 clo) for 1 h and then they were submitted to a standard cold air test in a climatic chamber for 2 h (Tdb = 1 degree C, rh = 40%-50%, wind speed = 0.8 m.s-1, nude), before and after 27 h of sleep deprivation. Thermoregulatory changes (rectal temperature, Tre; mean skin temperature. Tsk; metabolic heat production M) were monitored continuously. At comfortable ambient temperature, no significant change was observed after SD for Tre, Tsk and M. During the cold test, Tre did not change but Tsk and M were higher after SD (P < 0.05). Increased M (+ 6%, P < 0.05) was related to earlier and higher shivering, with a possible increase in the sensitivity of the thermoregulatory system as shown by the shorter time to onset of continuous shivering (d): 8.66 (SEM 1.33) min versus 28.20 (SEM 1.33) min (P < 0.001) and by a higher Tsk observed at d: 27.60 (SEM 1.40) degrees C versus 21.40 (SEM 0.60) degrees C (P < 0.001). These results were associated with higher cold sensations and shivering following SD. They also suggested that SD modified thermoregulatory responses at a central level especially in a cold environment.

Adult↗

Thermoregulatory responses of circum-pubertal children.

Passive temperature lability of nine circum-pubertal children [11.4 (1.2) years] was compared to that of nine young adult males [26.6 (5.2) years]. Each subject completed a 20-min period of exercise, followed immediately by post-exercise immersion in water at 28 degrees C. The aim of the exercise protocol was to induce a steady rate of sweating (Esw) while the postexercise immersion period induced cooling of the core region (tympanic temperature: Tty). The Tty values (relative to rest, delta Tty) at which sweating abated and at which shivering commenced were defined as the thresholds for the cessation of sweating and onset of shivering, respectively. While there was no significant difference between the delta Tty sweating thresholds, the onset of shivering, as reflected in the oxygen uptake (VO2) response, occurred at significantly higher (P < 0.05) delta Tty values in the children [mean (SD): - 0.07 (0.07) degrees C] than in the adults [ -0.22 (0.10) degrees C]. The slope of the Esw/delta Tty relationship was found to be significantly lower in the children (z = -5.64; P < 0.05), while the slopes of the VO2/delta Tty relationship were not significantly different (z = -0.84; P > 0.05). Skin blood perfusion was measured at the forehead (SkBP), and the slope of the SkBP/delta Tty relationship across the null-zone was significantly less in the children than in the adults (z = -2.13; P < 0.05) with the greatest reduction in perfusion occurring prior to the offset of sweating in the children. The subjective ratings of thermal comfort indicated that the children were more sensitive to changes in core temperature than the adults. It is concluded that maturation plays an important role in modifying thermoregulatory responses to deviations in core temperature. These results suggest that there may be differences in thermoregulatory "strategies" which are maturationally related.

Adolescent↗

Does cold acclimation induce nonshivering thermogenesis in juvenile birds? Experiments with Pekin ducklings and Japanese quail chicks.

The capability to produce heat in cold by nonshivering thermogenesis (NST) was studied in Pekin ducklings and Japanese quail chicks acclimated to cold for 3 weeks using indirect calorimetry (oxygen consumption) and electromyography from breast (M. pectoralis) and leg muscles (quails: M. gastrocnemius; ducklings: M. gastrocnemius, M. iliofibularis). Respiration of muscles in vitro was studied by measuring cytochrome c oxidase activity. In both species, cold acclimation induced clear morphometric and physiological changes, but no clear evidence of nonshivering thermogenesis. This was evident because increased shivering at least in one muscle coincided with increased oxygen consumption. In ducklings, however, amplitudes of shivering EMGs were low (<30 microV) in all muscles studied in both the control and cold-acclimated groups. Ducklings reacted to cold mainly by means of increasing body weight (1796 g in control, 2095 g in cold-acclimated) and circulatory changes. Acclimation did not change oxygen consumption either in vivo or in vitro. In quails, in addition to increased body weight (78.1 g control, 89.9 g cold-acclimated), improved insulation and metabolic adaptation to cold (increased respiration in vivo and in M. pectoralis in vitro) was also utilized. In Japanese quail chicks, 3 weeks of cold acclimation does not seem to induce NST, while in Pekin ducklings the existence of NST could not be totally excluded because of weak overall shivering activity.

Acclimatization↗

Effect of age and cold exposure on morphofunctional characteristics of skeletal muscle in neonatal pigs.

Muscular changes accompanying and/or promoting the rapid postnatal improvement of the thermogenic efficiency of shivering were investigated in piglets. Animals were obtained at birth or killed after 5 days at thermoneutrality (34-30 degrees C) or in the cold (24-15 degrees C), to stimulate intense shivering thermogenesis. Fast-twitch-glycolytic (longissimus lumborum) and slow-twitch-oxidative (rhomboid) muscles were prepared for electron microscopic examination and chemical measurements. Muscle-specific changes in energy stores and metabolism were observed after birth, including the switch from glycogen to lipids and variation of the lactate/pyruvate ratio corresponding to the progressive acquisition of the metabolic type of the mature muscles. There was major age-related and/or cold-induced development of the structures involved in excitation-contraction coupling (triadic profiles, +80% in the cold), oxidative metabolism (number of lipid droplets, +81% with age in the cold; number of mitochondria, +29% with age or cold; surface of mitochondrial inner membranes, +18% with age and +32% in the cold) and contraction potential (myofibril volume, +62% with age). In contrast, neither age nor cold affected capillary volume density and capillary-to-fibre ratio. The observed changes reflect the immaturity and remarkable plasticity of piglet skeletal muscle and are likely to underlie its enhanced capacity for shivering thermogenesis after birth.

Adipose Tissue↗

Effect of uniform and non-uniform skin temperature on thermal exchanges in water in humans.

We investigated the effect of uniform (UST) and non-uniform (NUST) skin temperature on thermal exchanges during a 3-h water immersion in five male subjects wearing (NUST) or not wearing (UST) a water-perfused garment. UST was achieved by immersing the nude subject in water up to the neck. For each subject, the water temperature was adjusted to the critical temperature ( T(cw), 31.4 +/- 0.9 degrees C) or 3 degrees C below T(cw) ( T(cw) - 3). NUST was achieved by perfusing different segments of the perfused garment with water of different temperatures. The water temperature of the segment was independently adjusted according to the skin temperature distribution in cold air, the mean skin temperature being the same as the UST. At T(cw) and T(cw) - 3, changes in esophageal and mean skin temperatures were identical in UST and NUST conditions, but the skin temperature of the trunk was higher and that of the limb was lower in the NUST condition. Heat production and the overall skin heat flux at T(cw) were identical in the two conditions, but those at T(cw) - 3 were about 25% lower ( P < 0.05) in NUST than in UST conditions. At T(cw) - 3, the overall tissue insulation was 36% higher ( P < 0.05) in NUST than in UST conditions, mainly because of higher limb insulation. Thermogenesis due to shivering was lower by 62% ( P < 0.05) in NUST than in UST. We conclude that the NUST condition increased tissue insulation and suppressed shivering. This suggests that a high skin temperature of the trunk attenuates shivering in cold water and increases the ability to defend body temperature more economically in cold water.

Adult↗

Role of glucagon in the control of heat production in ducklings.

Glucagon is known to be a central modulator of neural activity and a peripheral thermogenic effect. The purpose of this study was to better understand the role of glucagon in the control of heat production, shivering and particularly as a mediator of nonshivering thermogenesis (NST) in ducklings. In order to study the mechanism of NST, an intracerebroventricular (i.c.v.) injection of glucagon (10(-7) M) in to thermoneutral (TN), chronically glucagon treated (GT) and cold acclimatized (CA) ducklings exposed to acute cold (4 degrees C) or a thermoneutrality (25 degrees C), was performed. At 25 degrees C ambient temperature (Ta), the metabolic rate (MR) remained unchanged after glucagon injection. At 4 degrees C Ta i.c.v. glucagon injection, no significant change in MR was observed in GT and CA ducklings during 160 min of cold exposure, whereas there was 63% decrease in MR in (TN) ducklings (5.02 +/- 0.1 2 vs 7.91 +/- 0.1 4 W/kg(-1) p < 0.05). Shivering activity was completely suppressed in TN and GT ducklings after glucagon administration. The NST was estimated to be 3.26 W/kg. This findings suggest that glucagon administered into the brain has no thermogenic effect but could be involved in the central control of somatic motricity, and here we demonstrated for the first time, of our knowledge, that central glucagon have a role in the development of nonshivering thermogenesis during prolonged cold via an inhibition of shivering in birds.

Acclimatization↗

Thermoregulatory cold-defense deficits in rats with preoptic/anterior hypothalamic lesions.

This paper discusses the course of recovery from the thermoregulatory deficits produced in rats by electrolytic lesions in the preoptic/anterior hypothalamic area. Severe damage rendered rats ectothermic, that is unable to maintain their body temperatures at normal levels unless they were incubated at an ambient temperature of 30 degrees C. Less severe damage produced rats that maintained subnormal but stable body temperatures at 23 degrees C, but that did not increase metabolic rate or shiver and whose body temperatures dropped drastically in the cold (5 degrees C). As the animals recovered, nonshivering thermogenesis returned. Eventually the rats became excessively hyperthermic in normal room temperatures, due to very high metabolic rates. They were still unable to shiver or increase metabolic rate further in the cold and were therefore still unable to prevent a large drop in body temperature. Muscle tonus and shivering recovered gradually, and oxygen consumption returned to near normal levels. The data are described in terms of levels of integration of the nervous control of thermoregulation.

Animals↗

Early social isolation alters behavioral and physiological responses to an endotoxin challenge in piglets.

Psychosocial stress in the form of maternal deprivation and social isolation during early postnatal life induces persistent alterations in behavioral and physiological mechanisms of adaptation. One consequence may be an increased susceptibility to diseases in later life. Therefore, the aim of the present study was to investigate in domestic piglets the effects of a repeated social isolation (2 h daily from day 3 to day 11 of age) on behavioral, endocrine and immune responses to an endotoxin challenge with lipopolysaccharide (LPS) 1 day or 45 days after the isolation period. Peripheral LPS administration caused serious sickness behavior (somnolence, shivering, vomiting) and provoked profound increases in circulating tumor necrosis factor-alpha (TNF-alpha), ACTH and cortisol concentrations. The prior social isolation treatment enhanced signs of sickness and impaired suckling behavior. Early isolated piglets responded to LPS by an increase of shivering on day 12 and by increased vomiting on day 56 compared to controls. Further, there were considerable delays and reductions of time isolated piglets spent suckling on day 12. The repeated isolation stressor diminished TNF-alpha increases after LPS, whereas stress hormone levels were not significantly affected by isolation treatment. Finally, stronger relationships between signs of sickness and physiological measures were revealed in early isolated piglets. The duration of somnolence in isolated piglets was related to changes of cortisol and TNF-alpha concentrations, and the highest impact on duration of shivering was found for changes in cortisol and corticosteroid binding globulin levels. The present results suggest a sustained adaptive sensitization of coping with infection by social stress experience during early development in piglets.

Adrenocorticotropic Hormone↗

Misoprostol use during the third stage of labor.

OBJECTIVES: To systematically review the efficacy of misoprostol compared with placebo or other uterotonics in preventing maternal morbidity associated with the third stage of labor. METHODS: We identified, retrieved, evaluated, abstracted data, and assessed the quality of all published studies (from January 1996 to May 2002) which assessed misoprostol's efficacy in minimizing uterine blood loss during the third stage of labor. Seventeen studies included 28170 subjects; of these, approximately one-half received misoprostol with the remainder receiving either a placebo or another uterotonic agent. An estimate of the odds ratio (OR) and risk difference for dichotomous outcomes was calculated using a random- and fixed-effects model. Continuous outcomes were pooled using a variance-weighted average of within-study difference in means. RESULTS: In assessing studies comparing misoprostol with placebo, those who received oral misoprostol had a decreased risk of needing additional uterotonics (OR 0.64, 95% confidence interval 0.46, 0.90). Compared with placebo, use of misoprostol was associated with an increased risk for shivering and pyrexia. In contrast, in studies comparing misoprostol with oxytocin, oxytocin was associated with significantly lower rates of postpartum hemorrhage, maternal shivering and pyrexia. In studies comparing misoprostol with Syntometrine, misoprostol was associated with higher rates of the need for additional uterotonic agent as well as shivering. CONCLUSIONS: Misoprostol was inferior to oxytocin and other uterotonics with regard to any of the third stage of labor outcomes assessed. However, when compared to placebo, misoprostol had a decreased risk of needing additional uterotonics. Thus, in less-developed countries where administration of parenteral uterotonic drugs may be problematic, misoprostol represents a reasonable agent for the management of the third stage of labor. Additional randomized clinical trials examining objective outcome measures (i.e. need for blood transfusion or 10% hemoglobin change) may further define benefits and risks of misoprostol use during the third stage of labor.

Female↗

Pharmacokinetics and adverse-effect profile of rectally administered misoprostol in the third stage of labor.

OBJECTIVE: To characterize the pharmacokinetics and adverse-effect profile of rectally administered misoprostol. METHODS: To assess absorption of rectally administered misoprostol, 20 women were randomized to receive misoprostol 600 microg by either oral or rectal administration after delivery. Blood samples were obtained at 0, 7.5, 15, 30, 45, 60, 90, 120, and 240 minutes and analyzed for serum concentrations of misoprostol free acid by enzyme-linked immunosorbent assay. Additionally, 275 women were randomized to receive rectal 400 microg, rectal 600 microg, or oral 600 microg misoprostol after delivery. Self-assessment questionnaires were used to ascertain the adverse-effect profiles. RESULTS: Misoprostol tablets are absorbed rectally even though they are formulated for oral use. The area under the curve (integral of concentration and time graph) for rectal misoprostol was higher by 121 pg.h/mL (95% confidence interval [CI] -4.2, 246.2) than for oral misoprostol. The rectal route group had a mean maximum serum concentration 144 pg/mL lower than that for the oral route (95% CI 63, 225). This maximum was achieved on average 23 minutes later than in the oral group (95% CI 10, 35). Shivering was reported by 76% of the patients in the oral 600-microg arm, 56% of the patients in the rectal 400-microg arm, and 54% of the patients in the rectal 600-microg arm. The relative risk of shivering in the combined rectal groups is 73% that of the oral group (95% CI 61%, 86%). Severe shivering reported by patients was significantly reduced, by 72%, in rectal groups compared with the oral group (95% CI 60%, 81%). CONCLUSION: Misoprostol administered rectally is associated with lower peak levels and a reduction in adverse effects compared with the oral route. Increasing rectal doses may achieve higher efficacy without reducing the acceptability of the treatment.

Administration, Oral↗

Cardiovascular and thermoregulatory responses to vasotocin and angiotensin II in the pigeon.

The cardiovascular and thermoregulatory effects of intrahypothalamically (preoptic/anterior hypothalamus) and intravenously injected arginine vasotocin (AVT) and [Val5]angiotensin II (ANG II) were measured at 2 degrees C in the pigeon (Columba livia). In addition, the effects of intrahypothalamic and intravenous injections of AVT on respiratory rates were measured at 10-15 degrees C. Intrahypothalamic and intravenous AVT (500 ng and 20 micrograms/kg, respectively) reduced shivering and body temperature but had no effects on blood pressure, heart rate or respiratory rate. Intrahypothalamic (500 ng and 1 microgram) and intravenous (3 micrograms/kg) ANG II elevated blood pressure. If the blood pressure increased slowly, the shivering and body temperature also increased, whereas a rapid rise in blood pressure inhibited shivering and lowered body temperature. Intravenous ANG II produced tachycardia but intrahypothalamic ANG II did not affect the heart rate.

Angiotensin II↗

A preliminary study of cutaneous blood flow associated with postpartum use of oral misoprostol.

OBJECTIVE: To evaluate cutaneous blood flow, as identified by Doppler fluximetry, to understand the etiology of shivering associated with the postpartum use of oral misoprostol. METHODS: Eligible participants were recruited from a group of women who were enrolled in an ongoing randomized trial comparing 400 microg of oral misoprostol to 5 IU of intravenous oxytocin for postpartum hemorrhage prophylaxis. The laser Doppler fluximeter was used to noninvasively measure changes in peripheral tissue perfusion (flux). A skin probe attached to the upper arm recorded flux and skin temperature. Baseline levels were obtained before delivery and for 30 minutes postpartum (maximum flux) after the women received the study drug. Continuous variables were analyzed with Student t-test or paired t-test, with the Wilcoxon signed rank test used for non-parametric ordinal data. Categoric data were analyzed with the chi-square test or Fisher's exact test. RESULTS: Sixteen women were enrolled, and 10 women had a vaginal delivery and received the study drugs. Among these 10 women, a significant difference between baseline and maximum flux levels was demonstrated for both women treated with oxytocin (P = .04) and for those treated with misoprostol (P = .04). Women treated with oxytocin also had a significant change in skin temperature (P = .04). Maximum flux levels were not significantly different between the women receiving misoprostol compared with those receiving oxytocin (P = .42). CONCLUSIONS: Shivering associated with oral misoprostol may not be due to a resetting of the hypothalamic thermoregulatory centre. Further study is needed to determine whether shivering associated with oral misoprostol is dose-dependent or related to locally mediated phenomena.

Administration, Oral↗