Body Temperatures in the Elderly: A National Study of Physiological,Social, and Environmental Conditions

Two large-scale surveys of body temperatures in elderly people living at home were carried out in the winter of 1972. Most of the homes visited were cold with room temperatures below the minimum recommended by the Department of Health. Deep body temperatures below 35·5°C were found in 10% of those studied, and the difference between the skin temperature and the core temperature was also reduced in this group. Such individuals are at risk of developing hypothermia since they show evidence of some degree of thermoregulatory failure. Further research is needed, but meanwhile there are practical measures that could be taken to reduce the risk of hypothermia in the elderly.     

Effects of orexins on energy balance and thermoregulation

Intracerebroventricular injections of 10-20-microg orexin-A induce food intake in rats for about 30 min, or enhance fasting-induced hyperphagia. In thermoregulatory studies, an amount of 2 microg of the peptide causes hypometabolism and hypothermia in the same period. The thermoregulatory reaction can be demonstrated at moderately cool environments, mainly after slight food deprivation. Both the ingestive and the thermoregulatory reactions are more pronounced in cold-adapted animals. Pretreatment with D-Tyr27,36,D-Thr32-NPY(27-36), a peptide-antagonist of NPY, prevents the hypothermia. It is concluded that, probably through NPY activation, orexin-A is involved primarily in the regulation of energy status of the body (as an anabolic agent), and not simply in the regulation of either food intake or body temperature. This anabolic response is followed by a late and more sustained catabolic phase characterized by absence of food intake, increased metabolism and dose-dependent hyperthermia, which hyperthermia cannot be suppressed by the NPY-antagonist. In contrast to orexin-A, neither hyperphagia nor suppression of refeeding hyperphagia, but dose-dependent hyperthermia follows injections of orexin-B, suggesting that this peptide has neither coordinated anabolic nor coordinated catabolic effects on energy balance.     

Heat increment of feeding and its thermoregulatory benefit in the muskrat (Ondatra zibethicus)

The calorigenic effect of feeding and its potential benefit in defraying thermoregulatory costs and attenuating immersion hypothermia of adult muskrats were investigated. A single session of feeding on aquatic vegetation was sufficient to raise the metabolic rate of muskrats for a period of at least 5 h. The peak postprandial rate of oxygen consumption averaged 1.42 times the level established for fasted animals, and the heat increment of feeding accounted for about 40% of the metabolizable energy intake of muskrats. There was no evidence of a postprandial rise in oxygen consumption of muskrats that entered water at 18–19°C after feeding. In aquatic trials, average and minimum steady-state oxygen consumption rates of fed muskrats were similar to, or even lower than values recorded from fasted animals, implying substitution of heat increment of feeding for thermoregulatory heat production. Our data did not support the hypothesis that heat increment of feeding retards body cooling in water. Net body temperature decline in water was actually higher in fed animals than in fasted controls. However, since previously fed muskrats also entered water at an elevated body temperature, the final body temperature (at 30 min immersion) was similar in all groups. These findings suggest that metabolic heat generated incidental to preimmersion feeding could provide a thermoregulatory benefit to muskrats by reducing the need for active thermogenesis in water.     

Role of adenosine in the hypoxia-induced hypothermia of toads

The concept that hypoxia elicits a drop in body temperature (T(b)) in a wide variety of animals is not new, but the mechanisms remain unclear. We tested the hypothesis that adenosine mediates hypoxia-induced hypothermia in toads. Measurements of selected T(b) were performed using a thermal gradient. Animals were injected (into the lymph sac or intracerebroventricularly) with aminophylline (an adenosine receptor antagonist) followed by an 11-h period of hypoxia (7% O(2)) or normoxia exposure. Control animals received saline injections. Hypoxia elicited a drop in T(b) from 24.8 +/- 0.3 to 19. 5 +/- 1.1 degrees C (P < 0.05). Systemically applied aminophylline (25 mg/kg) did not change T(b) during normoxia, indicating that adenosine does not alter normal thermoregulatory function. However, aminophylline (25 mg/kg) significantly blunted hypoxia-induced hypothermia (P < 0.05). To assess the role of central thermoregulatory mechanisms, a smaller dose of aminophylline (0.25 mg/kg), which did not alter hypoxia-induced hypothermia systemically, was injected into the fourth cerebral ventricle. Intracerebroventricular injection of aminophylline (0.25 mg/kg) caused no significant change in T(b) under normoxia, but it abolished hypoxia-induced hypothermia. The present data indicate that adenosine is a central and possibly peripheral mediator of hypoxia-induced hypothermia.     

5-HT1A受体阻断剂对乙醇引起大鼠低体温和行为性体温调节反应的影响

目的：观察5-羟色胺1A （5-HT_1A）受体阻断剂p-MPPI对乙醇引起大鼠低体温和行为性体温调节反应的影响。方法：用无线遥控测温技术记录成年雄性SD大鼠体核温度和活动的变化。用无线遥测温度梯度仪监测大鼠体核温度和行为性体温调节活动,将大鼠置于15℃~40℃的温度梯度箱内,并允许动物自由选择箱内温度,观察乙醇（3 g/kg）引起低体温和行为性体温调节的反应以及5-HT_1A受体阻断剂p-MPPI （1 mg/kg）对其效应的影响。结果：①乙醇能引起大鼠快速的体温降低反应,同时动物选择较低的环境温度。②5-HT_1A受体阻断剂p-MPPI能明显阻断乙醇引起的低体温和行为性体温调节变化。结论：①乙醇能使体温调定点降低,因为乙醇引起低体温时,大鼠选择较冷环境温度区;②5-HT可能参与乙醇引起低体温与行为性体温调节活动。     

Behavioral thermoregulation by hypoxic rats.

To address whether a shift in hypothalamic thermal setpoint might be a significant factor in induction of hypoxic hypothermia, behavioral thermoregulation was examined in 7 female Sprague-Dawley rats implanted with radiotelethermometers for deep body temperature (Tb) measurement in a thermocline during normoxia (PO2 = 125 torr) and hypoxia (PO2 = 60 torr). Normoxic rats (TNox) selected a mean ambient temperature of 19.7 +/- 1.4 (SE) degrees C and maintained Tb at 37.0 +/- 0.2 degrees C. Hypoxic rats selected a significantly higher ambient temperature (THox = 28.6 +/- 2.2 degrees C) but maintained Tb significantly lower at 35.5 +/- 0.3 degrees C. Without a thermal gradient (ambient temperature = 25 degrees C), Tb during hypoxia was 35.4 +/- 0.4 degrees C. The maintenance of a lower body temperature during hypoxia through behavioral thermoregulation despite having warmer temperatures available supports the hypothesis that the thermoregulatory setpoint of hypoxic rats is shifted to promote thermoregulation at a lower Tb, effectively reducing oxygen demand when oxygen supply is limited.     

Histidine induced hypothermia in the rat

The mechanism by which systemic injection of histidine induces hypothermia has been studied in rats. Injection of histidine directly into the rostral hypothalamic thermoregulatory centers, at sites at which histamine causes hypothermia, had no effect on body temperature. Systemic histidine laoding did not change the hypothalamic or whole brain levels of norepinephrine, dopamine or 5-HT, indicating that the fall in temperature is not due to depletion of these amines which are known to be involved in thermoregulation. Blood pressure measurements showed that when histidine was administered to rats pretreated with a peripherally acting histidine decarboxylase inhibitor no appreciable amount of systemic histamine was formed. It is concluded that the hypothermic effect of histidine is due to the increased formation of histamine in the brain.     

Effects of cold and capsaicin desensitization on prostaglandin E hypothermia in rats

Intraperitoneal injection of prostaglandin E1 (PGE) produces a transient hypothermia in rats that lasts 1-2 h. Rats exposed to an ambient temperature (Ta) of 26 degrees C displayed a decrease in rectal temperature (Tre) of 0.95 +/- 0.12 degrees C (SE) after injection with PGE (100 micrograms/kg ip). Hypothermia was produced mainly by heat losses, as indicated by increases in tail blood flow. At Ta of 4 degrees C, PGE produced a comparable fall in Tre of 1.00 +/- 0.14 degrees C. However, in the cold the hypothermia was caused solely by decreases in heat production. These results indicate that the PGE-induced hypothermia is not the result of a peripheral vasodilation induced by the direct action of PGE on the tail vascular smooth muscle but is a central nervous system-mediated response of the thermoregulatory system induced by PGE within the peritoneal cavity. Capsaicin injected subcutaneously induces a transient hypothermia in rats because of stimulation of the warm receptors. If administered peripherally in sufficient amounts, it is reputed to impair peripheral warm receptors so that they become desensitized to the hypothermic effects of capsaicin. We measured PGE-induced hypothermias in rats both before and after capsaicin desensitization at Ta of 26 degrees C. Before desensitization the hypothermia was -1.14 +/- 0.12 degrees C, whereas after capsaicin treatment the PGE-induced hypothermia was -0.34 +/- 0.17 degrees C. The biological effects of capsaicin are diverse; however, based on current thinking about the thermoregulatory effects of capsaicin desensitization, our results indicate that peripheral warm receptor pathways are in some manner implicated in the hypothermia induced by intraperitoneal PGE.     

Bombesin produces hypothermia in hypophysectomized rats

Intracerebroventricular administration of bombesin, a naturally-occurring peptide, produces hypothermia in the rat. To determine whether a pituitary-dependent step is necessary for this effect, the thermoregulatory response was followed in hypophysectomized and intact rats maintained at room temperature. Significant hypothermia was produced in both experimental groups. This study supports an extra-pituitary mechanism for bombesin-induced hypothermia.     

Cosignaling of adenosine and adenosine triphosphate in hypobaric hypoxia-induced hypothermia

Purines, that is, adenosine and ATP, are not only products of metabolism but are also neurotransmitters. Indeed, purinergic neurotransmission is involved in thermoregulatory processes that occur during normoxia. Exposure to severe hypoxia elicits a sharp decrease in body core temperature (T(CO)), and adenosinergic mechanisms have been suspected to be responsible for this hypothermia. Because ATP per se and its metabolite adenosine could have complex interactions in some neural networks, we hypothesize that both adenosine and ATP are involved in the central mechanism of hypoxia-induced hypothermia. Their role in the thermoregulatory process was therefore investigated in a 24-h hypobaric hypoxia (Fi(O2) = 10%), using CGS-15943, a nonselective antagonist of adenosine receptors, and suramin, an ATP receptor antagonist. T(CO) and spontaneous activity (A(S)) were monitored by telemetry in conscious rats, receiving CGS-15943 (10 mg/kg ip), suramin (7 nmol icv), or both. The same treatments were done in normoxia to evaluate the specificity of their thermoregulatory action observed in hypoxia. Suramin/CGS-15943 treatment blunted the profound hypothermia observed in control rats throughout the hypoxia exposure, whereas CGS-15943 treatment blunted hypothermia during only 3 h, and suramin treatment had no effect. These results suggest that suramin potentiates the CGS-15943 effects and consequently that adenosine and ATP signaling act in synergy. In normoxia, suramin/CGS-15943 induced an increase in T(CO) but to a far lesser extent than observed in hypoxia. Thus it might be suggested that the suramin/CGS-15943 blunting of hypoxia-induced hypothermia would be specific to hypoxia-induced mechanisms.     

氧化震颤素在精氨酸加压素引起大鼠低温中的作用与对行为性体温调节反应的影响

目的:研究氧化震颤素在精氨酸加压素(AVP)引起低温中的作用及其对行为性体温调节反应的影响。方法:无线遥控测温技术记录成年雌性SD大鼠体核温度(Tc)、棕色脂肪组织(BAT)温度和活动的变化。用无线遥测温度梯度仪记录大鼠行为性体温调节反应。分别观察AVP(10μg/kg)和氧化震颤素(0.25 mg/kg)对大鼠Tc、活动、BAT温度(TBAT)、理毛活动和行为性体温调节反应的影响。结果:AVP和氧化震颤素均能引起Tc和TBAT降低,理毛活动增加,引起低温反应的同时动物选择较低环境温度。氧化震颤素能使AVP引起的Tc和TBAT降低,以及理毛活动的增加更明显,并持续更长时间。注射氧化震颤素后立即注射AVP动物亦选择较低环境温度,但与AVP比较无明显差异。结论:AVP引起的低温与体温调定点下移、抑制BAT产热和增加理毛活动有关。氧化震颤素可能通过影响BAT产热和行为性体温调节参与外周给AVP引起的低温过程。     

Thyrotropin-releasing hormone action in the preoptic/anterior hypothalamus decreases thermoregulatory set point in ground squirrels.

Earlier work has shown that thyrotropin releasing hormone (TRH) produces dose-dependent decreases in body temperature (Tb) and metabolic rate when microinjected into the dorsal hippocampus (HPC) or preoptic/anterior hypothalamus (PO/AH) of awake ground squirrels. This study employed a behavioral paradigm to investigate the possibility that TRH-induced hypothermia is associated with a decrease in thermoregulatory set point. Six animals were successfully trained to press a bar for radiant heat escape and cool air reinforcement in order to obtain a cooler ambient temperature (Ta). During experimental testing, the animals were microinjected remotely with TRH (10-1000 ng/microliters) or a control solution (sterile saline or TRH-OH) into the PO/AH. The micro-injections were delivered via bilateral injection cannulae inserted through chronic bilateral cannula guides that had been stereotaxically implanted under pentobarbital anesthesia. Cumulative and time-integrated bar presses were obtained on a computer generated display. Tb, measured in the brain via a bead-type thermistor, and chamber Ta were recorded continuously. Following TRH administration, a significant increase in mean bar-press rate was observed during the period in which Tb was falling, when compared to a comparable time period just prior to the microinjection. These findings complement results obtained from four animals that were trained to press a bar for heat reinforcement in a cold (- 10 degrees C) environment. In this alternative behavioral paradigm, microinjection of TRH into the PO/AH or HPC induced a decrease in mean bar-press rate as Tb was falling. The results support the hypothesis that TRH-induced hypothermia in golden-mantled ground squirrels is achieved by lowering thermoregulatory set point.     

Mechanism of fasting heterothermia and re-feeding normothermia in mice

Mice subjected to caloric restriction (CR) typically display heterothermia characterized by hypothermia in the daytime and normothermia at night. The possible thermoregulatory mechanisms that mediate the CR-induced daytime hypothermia or the recovery of core temperature upon re-feeding are not well understood. In the present study drugs that inhibit three different pathways of thermogenesis were applied before, during and after CR in mice, while core temperature was monitored by biotelemetry. The time course of core temperature during complete CR and re-feeding was not modified by administration of the postganglionic adrenergic blocker guanethidine (10 mg/kg/day). Administration of the centrally acting muscle relaxant mephenesin (42 mg/kg/day) exacerbated the CR-induced hypothermia. Administration of the nonspecific opioid antagonist naloxone (20 mg/kg/day) also exacerbated the CR-induced hypothermia. None of the drugs had any effect on the rate of the rise in core temperature during re-feeding after a fast. It is concluded that mice may rely on the heat from motor activity to remain normothermic during the first night of complete fasting. Shivering thermogenesis appears to be critical in thermoregulation during fasting. Furthermore, opiate-dependent thermogenesis may also contribute to the regulation of body temperature during the second night of fasting.     

Microwave radiation (2450 MHz) alters the endotoxin-induced hypothermic response of rats

The parenteral administration of bacterial endotoxin to rats causes a hypothermia that is maximal after approximately 90 minutes. When endotoxin-injected rats were held in a controlled environment at 22°C and 50% relative humidity and exposed for 90 minutes to microwaves (2450 MHz, CW) at 1 mW/cm², significant increases were observed in body temperature compared with endotoxintreated, sham-irradiated rats. The magnitude of the response was related to power density (10 mW/cm² > 5 mW/cm² > 1 mW/cm²). Saline-injected rats exposed for 90 minutes at 5 mW/cm² (specific absorption rate approximately 1.0 mW/g) showed no significant increase in body temperature compared with saline-injected, sham-irradiated rats. The hypothermia induced by endotoxin in rats was also found to be affected by ambient temperature alone. Increases in ambient temperature above 22°C in the absence of microwaves caused a concomitant increase in body temperature. This study reveals that subtle microwave heating is detectable in endotoxin-treated rats that have an impaired thermoregulatory capability. These results indicate that the interpretation of microwave-induced biological effects observed in animals at comparable rates and levels of energy absorption should include a consideration of the thermogenic potential of microwaves.     

Effects of lipopolysaccharide and acclimation temperature on induced behavioral fever in juvenile Iguana iguana

We examined the effects of acclimation temperature and two doses (2.5 and 25mgkg(-1)) of a pyrogen (lipopolysaccharide, LPS) on behavioral thermoregulation in juvenile green iguanas. Overall means of body temperatures for the three-day trial periods were compared among three groups of animals acclimated at 15, 25, and 34 degrees C. The responses of each group of animals to the two dosages of LPS and a control saline injection were examined. Within each treatment block, animals either chose high body temperatures characteristic of a fever response or chose low body temperatures characteristic of a hypothermic response. Thermoregulation was influenced by interaction effects between and among, and independent effects of, acclimation temperature, dose of LPS, and day. In some treatment blocks, individual lizard mass positively correlated with mean individual body temperature. Mean mass of lizards that chose higher body temperatures within a treatment block was higher than the mean mass of lizards that chose lower body temperatures. From these results, we concluded that LPS may induce two different behavioral thermoregulatory responses: fever or hypothermia. The actual amplitude and direction of body temperature change appears to be affected by acclimation temperature and possibly by mass or energy reserves of the animal. If the energy reserves are not sufficient to sustain the higher rate of metabolism associated with the higher body temperatures of a hyperthermic or feverish state, the animal may resort to hypothermia.     

Effects of GABA-transaminase inhibitor Vigabatrin on thermoregulation in rats

Vigabatrin is a GABA derivative (gamma-vinyl GABA) which inhibits irreversibly the enzyme activity of GABA transaminase and thus increased indirectly brain GABA concentrations. We have used body temperature assay to examine the effects of Vigabatrin on thermoregulation in intact rats. In order to understand the mechanism of thermoregulatory action of Vigabatrin at cellular level, we have investigated its effect on individual warm-sensitive preoptic area/anterior hypothalamus (PO/AH) neurons in rat brain slice preparations. The results of the present study suggest that Vigabatrin produced dose-dependent hypothermia in rats and also increased temperature sensitivity of warm-sensitive PO/AH neurons.     

An experimental test of the thermoregulatory hypothesis for the evolution of endothermy

The thermoregulatory hypothesis proposes that endothermy in mammals and birds evolved as a thermoregulatory mechanism per se and that natural selection operated directly to increase body temperature and thermal stability through increments in resting metabolic rate. We experimentally tested this hypothesis by measuring the thermoregulatory consequences of increased metabolic rate in resting lizards (Varanus exanthematicus). A large metabolic increment was induced by feeding the animals and consequent changes in metabolic rate and body temperature were monitored. Although metabolic rate tripled at 32 degrees C and quadrupled at 35 degrees C, body temperature rose only about 0.5 degrees C. The rate of decline of body temperature in a colder environment did not decrease as metabolic rate increased. Thus, increasing the visceral metabolic rate of this ectothermic lizard established neither consequential endothermy nor homeothermy. These results are inconsistent with a thermoregulatory explanation for the evolution of endothermy.     

Neue Ergebnisse über die Arbeitshyperthermie des Menschen

Nielsen (1938) demonstrated that hypothermia during exercise is independent of room temperature within a range from 5° to 32° C. Subsequently, other investigators confirmed this observation. From these results,Asmussen &Nielsen (1947) concluded that a resetting of the thermoregulatory centre brought about by impulses reaching the brain from the working muscles or from the motor centres takes place. In order to find out whether impulses from motor centres really affect the thermoregulatory centres, we tried, by administration of curare in human beings, to increase the frequency of impulses necessary to bring about a certain amount of mechanical work. However, in 2 series of experiments at room temperatures of 23° and 34° C respectively and at a constant work output of 3 mkp/sec, no significant differences in body temperature (measured in the lower esophagus) before and during curare infusion could be detected. In the resting conditions, curare exerts no influence on body temperature. In normal subjects performing low work (3 mkp/sec) the body temperature decreases at a room temperature of 23° C but increases at a room temperature of 32° C. In conclusion, the hyperthermia during exercise cannot be due to a resetting of thermoregulatory centres. It works rather like a proportional closed loop control system. The relative independence of the hyperthermia from the environmental temperature suggests a considerable influence of the latter parameter via the thermoreceptors of the skin on the thermoregulation during work.     

Baroreflex modulation of peripheral vasoconstriction during progressive hypothermia in anesthetized humans

Mild hypothermia is a major concomitant of surgery under general anesthesia. We examined the hypothesis that baroreceptor loading/unloading modifies thermoregulatory peripheral vasoconstriction and, consequently, body core temperature in subjects undergoing lower abdominal surgery with general anesthesia. Thirty-six patients were divided into four groups: control group (C), applied positive end-expiratory pressure (PEEP; 10 cmH(2)O) group (P), applied leg-up position group (L), and a group of leg-up position patients with PEEP starting 90 min after induction of anesthesia (L + P). The esophageal temperature (T(es)) and the forearm-fingertip temperature gradient, as an index of peripheral vasoconstriction, were monitored for 3 h after induction of anesthesia. Mean arterial pressure and pulse pressure did not change during the study in any group. The change in right atrial transmural pressure from the baseline value was 0.3 +/- 0.1 mmHg in C, -3.0 +/- 0.5 mmHg in P, and 2.3 +/- 0.4 mmHg in L (P < 0.01). The change in T(es) at the end of the study was -1.7 +/- 0.1 (35.1 +/- 0.1) degrees C in C, -1.1 +/- 0.1 (35.7 +/- 0.1) degrees C in P, and -2.7 +/- 0.1 (34.1 +/- 0.1) degrees C in L, showing significant differences (P < 0.01). The T(es) threshold for thermal peripheral vasoconstriction was 35.6 +/- 0.1 degrees C in C, 36.2 +/- 0.2 degrees C in P, and 34.8 +/- 0.2 degrees C in L (P < 0.01). Excessive T(es) decrease in the leg-up-position operation was attenuated by applying PEEP (L + P group; P < 0.05). Our data indicate that baroreceptor loading augments and unloading prevents perioperative hypothermia in anesthetized and paralyzed subjects by reducing and increasing the body temperature threshold for peripheral vasoconstriction, respectively.     

The effects of pentobarbital, fentanyl-droperidol, ketamine-xylazine and ketamine-diazepam on core and surface body temperature regulation in adult male rats

Many commonly used anesthetics cause hypothermia by inhibiting central and peripheral thermoregulatory mechanisms. Although it is probable that a loss of thermal homeostasis contributes directly to the high mortality frequently reported following anesthesia of laboratory rodents, this adverse effect has been investigated rarely in the past. This study compared the effects of three parenteral anesthetics (pentobarbital, ketamine-xylazine and ketamine-diazepam) and a neuroleptanalgesic (fentanyl-droperidol) on core and surface body temperature regulation in rats. Results showed a profound hypothermia with all dosages of pentobarbital, while ketamine-xylazine and ketamine-diazepam caused a dose-dependent depression in core and surface body temperature. All dosages of fentanyl-droperidol (Innovar-Vet) caused minimal depression in thermoregulation, suggesting that it is the drug which requires the least external thermal support. Results of this study also suggested that inability to compensate for heat loss, particularly from the body core, may profoundly influence anesthetic toxicity and the safety of anesthetic procedures.