Cold-induced fever and peak metabolic rate in the nine-banded armadillo (Dasypus novemcinctus)

In response to cold exposure, some mammals, including the nine-banded armadillo (Dasypus novemcinctus), exhibit an increase in core temperature. This response, which can be qualified as a cold-induced fever, could increase cold tolerance by increasing peak metabolic rates because of the Q(10) effects. This hypothesis, however, is not compatible with the observation that peak core temperature can occur up to 100 min before peak metabolic rate in nine-banded armadillos during acute exposure to cold heliox (79% He; 21% O(2)). This temporal separation between the timing of peak metabolic rate and core temperature could be the result of regional heterothermy, of the confounding effects of activity, or of using heliox as a respiratory gas. We tested these potential sources of error by exposing nine-banded armadillos to cold air while simultaneously monitoring behavior, metabolic rates (V dot o2 and V dot co2), and four core temperatures. Cold air exposure resulted in a smaller but significant temporal separation, with peak core temperature occurring on average 10 min before peak metabolic rate. Animals exhibited low activity levels, and the four core temperatures changed according to the same temporal pattern, thus eliminating the possibility that activity or regional heterothermy caused the temporal separation. Using a conceptual model, we propose that the temporal separation resulted from a rate of cooling that was too fast.     

Effect of alcohol on thermal balance of man in cold water.

The effects of alcohol on core cooling rates (rectal and tympanic), skin temperatures, and metabolic rate were determined for 10 subjects rendered hypothermic by immersion for 45 min in 10 degrees C water. Experiments were duplicated with and without a 20-min period of exercise at the beginning of cold water immersion. Measurements were continued during rewarming in a hot bath. With blood alcohol concentrations averaging 82 mg 100 mL-1, core cooling rates and changes in skin temperatures were insignificantly different from controls, even if the exercise period was imposed. Alcohol reduced shivering metabolic rate by an overall mean of 13%, insufficient to affect cooling rate. Alcohol had no effect on metabolic rate during exercise. During rewarming by hot bath, the amount of 'afterdrop' and rate of increase in core temperature were unaffected by alcohol. It was concluded that alcohol in a moderate dosage does not influence the rate of progress into hypothermia or subsequent, efficient rewarming. This emphasizes that the high incidence of alcohol involvement in water-related fatalities is due to alcohol potentiation of accidents rather than any direct effects on cold water survival, although very high doses of alcohol leading to unconsciousness would increase rate of progress into hypothermia.     

Effects of cold adaptation and noradrenaline on thermosensitivity of rat hypothalamic neurons studiedin vitro

The experiments performed on rat brain slices have shown that cold adaptation of an animal influences the thermosensitivity of hypothalamic medial preoptical neurons. The adaptation is followed by an increase in the proportion of 38–41°C-thermoresponsive neurons and by a decrease in the proportion of 35–38°C-thermoresponsive units. In control animals, noradrenaline (NA) increased the responses of hypothalamic neurons to the action of 35–38°C temperature and decreased them to the action of 38–41°C temperature. Cold adaptation prevented the effects of NA on neuronal thermosensitivity, which suggests that their NA sensitivity is modified by cold adaptation.Neirofiziologiya/Neurophysiology, Vol. 26, No. 3, pp. 171–176, May–June, 1994.     

Role of beta adrenoceptors in metabolic and cardiovascular responses of cold exposed humans

Effect of a nonspecific beta adrenergic blocker — propranolol (40 mg per os) on thermoregulatory responses of cold water immersed (12.5°C) humans was studied. Propranolol attenuates resting and cold induced thermogenesis, rectal temperature, heart rate and systolic blood pressure, but increases production of adrenaline and cortisol. Propranolol has no effect on the threshold body temperature for induction of cold thermogenesis and on central thermosensitivity. The following conclusions are drawn from consideration of the data presented: During the early phase of cooling (20 min after the start of cooling) the thermogenesis mediated by beta adrenergic receptors may cover about 80% of the total metabolic increase induced by cold. After about 30 min of cooling the relative proportion of beta adrenergic thermogenesis starts to decline, reaching 20% of the total cold thermogenesis at the end of cooling.

It can be suggested from consideration of the data that, in man, the beta adrenergic receptors in the heart, blood vessels, adipocytes and muscles participate in mediating effect of cold on cardiovascular and thermoregulatory responses. Furthermore, these data imply that human adrenergic thermogenesis is produced outside of the brown adipose tissue. Thus, physiological mechanisms mediating adrenergic thermogenesis in humans appear to be different from those in small mammals.     

TRPV1 gene required for thermosensory transduction and anticipatory secretion from vasopressin neurons during hyperthermia

Increases in core body temperature promote thermoregulatory cooling by stimulating sweat production and preemptive renal water reabsorption through the release of vasopressin (VP, antidiuretic hormone). The mechanism by which the hypothalamus orchestrates this anticipatory VP release during hyperthermia is unknown but has been linked to a central thermosensory mechanism. Here, we report that thermal stimuli spanning core body temperatures activate a calcium-permeable, ruthenium red- and SB366791-sensitive nonselective cation conductance in hypothalamic VP neurons. This response is associated with a depolarizing receptor potential and an increase in action potential firing rate, indicating that these neurons are intrinsically thermosensitive. The thermosensitivity of VP neurons isolated from trpv1 knockout (Trpv1(-/-)) mice was significantly lower than that of wild-type counterparts. Moreover, Trpv1(-/-) mice showed an impaired VP response to hyperthermia in vivo. Channels encoded by the trpv1 gene thus confer thermosensitivity in central VP neurons and contribute to the thermal control of VP release in vivo.     

Repeated exposures to cold and the relationship between skin and core temperatures in control of metabolic rate in the goat (Capra hircus)

1. After 10-12 experiments in each of three goats, in which skin or core temperatures were lowered while the other temperatures remained sufficiently high to prevent metabolic rate from increasing, the core temperature threshold of shivering was lowered by 0.35 degrees C. 2. After 10-15 experiments, in which skin and core temperatures were simultaneously lowered to induce major increases of metabolic rate, no further change of threshold was observed, while the slope of metabolic rate over core temperature was reduced. 3. It is concluded that repeated cold exposures without manifest shivering can induce tolerance adaptation to cold.     

Static response in body temperature regulation of the euthermic warm-acclimated golden hamster (Mesocricetus auratus)

A characteristic feature of the body temperature regulation of euthermic golden hamsters is a great individual variability of body temperature in the thermoneutral zone. Resting values of the total metabolic rate (M) at ambient temperature 30-34 degrees C vary from 5.3 to 8.8 W.kg-1 between individuals, body temperature reaching 33.5-37.7 degrees C (subcutaneous temperature, Ts) and 35.4-39.0 degrees C (hypothalamic temperature, Th). The dependence of metabolic heat production on steady deviations of peripheral and central body temperature from the resting values in nonlinear in general, but the unknown functional relationship delta M = f (delta Th, delta Ts) can be replaced by a single linear regression function of Ts by neglecting the change of central body temperature: delta M = 2.14-2.00. delta Ts. Total body thermosensitivity of the golden hamster determined from steady changes of rectal temperature and metabolic rate after external cooling is -6.8 +/- 1.3 W.kg-1. degrees C-1.     

Thermal, cardiac and adrenergic responses to repeated local cooling

The aim of this study was to ascertain whether repeated local cooling induces the same or different adaptational responses as repeated whole body cooling. Repeated cooling of the legs (immersion into 12 degrees C water up to the knees for 30 min, 20 times during 4 weeks = local cold adaptation - LCA) attenuated the initial increase in heart rate and blood pressure currently observed in control subjects immersed in cold water up to the knees. After LCA the initial skin temperature decrease tended to be lower, indicating reduced vasoconstriction. Heart rate and systolic blood pressure appeared to be generally lower during rest and during the time course of cooling in LCA humans, when compared to controls. All these changes seem to indicate attenuation of the sympathetic tone. In contrast, the sustained skin temperature in different areas of the body (finger, palm, forearm, thigh, chest) appeared to be generally lower in LCA subjects than in controls (except for temperatures on the forehead). Plasma levels of catecholamines (measured 20 and 40 min after the onset of cooling) were also not influenced by local cold adaptation. Locally cold adapted subjects, when exposed to whole body cold water immersion test, showed no change in the threshold temperature for induction of cold thermogenesis. This indicates that the hypothermic type of cold adaptation, typically occurring after systemic cold adaptation, does not appear after local cold adaptation of the intensity used. It is concluded that in humans the cold adaptation due to repeated local cooling of legs induces different physiological changes than systemic cold adaptation.     

Effect of TRPM8 ion channel activation on thermoregulatory response to cooling

In rats, the effect of activation of the cold- and menthol-sensitive TRPM8 ion channel on different thermoregulatory parameters: total oxygen consumption, carbon dioxide release, respiration coefficient, constriction response of skin blood vessels, muscle activity, was studied. Activation of TRPM8 with menthol even in thermoneutral conditions produces an increase in oxygen consumption and a decrease in respiratory coefficient, which may suggest enhanced non-shivering thermogenesis and lipolysis. Rapid cooling against the background of TRPM8 activation is characterized by a decrease in the temperature thresholds of all thermoregulatory responses without associated changes in sequences of their initiation as well as in enhancement of metabolic component of emergency thermogenesis which leads to improved maintenance of core temperature in conditions when external cold acts on the organism. The obtained data on the effect of TRPM8 activation on metabolic parameters in thermoneutral conditions and under cooling suggest acontinuous involvement of this receptor in regulation of total metabolism and, possibly, in determination of the type of organism's metabolism as well as in determination of organism's response to external cooling.     

Mechanism of action of physical antipyresis in the rat

To study the mechanism of action of physical antipyresis, core temperature was measured in two groups of rats in which heat loss was increased by cold exposure and by cooling an inferior cava heat exchanger, respectively, both before and after infection with Salmonella enteritidis. Cold exposure did not influence core temperature. On the other hand, cooling the heat exchanger caused a fall in core temperature of approximately 0.7 degree C, to 37 degrees C in normothermia and to 38.5 degrees C 24 h after the infection. These lower core temperatures were then regulated against any further increase in heat loss until the thermoregulatory metabolic capacity of the animals was exhausted and a hypothermia developed. It is concluded that in infectious fever the threshold temperature of shivering increases as much as core temperature. Furthermore it is suggested that physical antipyresis, such as sponging with tepid water, induces a moderate but regulated fall in temperature to about the threshold of shivering and that its efficacy may increase with ambient temperature.     

Early development of neuronal hypothalamic thermosensitivity in birds: influence of epigenetic temperature adaptation

The aim of the study was to investigate the prenatal influence of different incubation temperatures on the early postnatal development of neuronal hypothalamic thermosensitivity in birds. The experiments were carried out in brain slices of 1-, 5- and 10-days-old Muscovy ducklings incubated at 35, 37.5 (control) or 38.5 degrees C during the last week of incubation. Firing rate of neuronal activity was recorded extracellularly during sinusoidal temperature changes. The results show that the temperature experienced prenatally has a clear influence on postnatal neuronal hypothalamic thermosensitivity. For instance, at the 10th day post-hatching, exposure to the cooler prenatal incubation temperature resulted in elevated neuronal hypothalamic warm sensitivity through an increased proportion of warm sensitive neurons and a reduced proportion of cold sensitive neurons in comparison with the control group. Exposure to the warmer prenatal incubation temperature induced the opposite effect. In these age group changes in neuronal hypothalamic thermosensitivity occur in relation to the prenatal temperature experienced (proximate adaptive). During the first days of life, prenatal temperature load induced a significant change in the thermosensitivity of hypothalamic neurons which was independent of the direction of change in incubation temperature in comparison with control conditions (proximate non-adaptive). Changes in the thermosensitivity of hypothalamic neurons after prenatal temperature experiences observed in all age groups may be the result of epigenetic temperature adaptation.     

General and local cold adaptation after a ski journey in a severe arctic environment.

It is hypothesized that some of the variability in the conclusions of several human cold adaptation studies could be explained if not only were the changes in core and shell temperatures taken into account, before and after cold adaptation, but also the absolute temperatures and metabolic rate in both thermally neutral environments and in the cold. Such an approach was used in a group of volunteers before and after a ski journey (3 weeks at -20 to -30 degrees C) across Greenland. Eight subjects were submitted to cold tests (Tdb = 1 degree C, r.h. = 40%, wind speed = 0.8 m.s-1) for 2 hours. Thermoregulatory changes were also monitored in a neutral environment (Tdb = 30 degrees C). In the neutral environment, the arctic journey increased metabolic rate (11.2%; P less than 0.05) and mean skin temperature [Tsk: 33.5 (SEM 0.2) degrees C vs 32.9 (SEM 0.2) degrees C, P less than 0.05]. During the cold test, the arctic journey was associated with a lower final rectal temperature [36.8 (SEM 0.2) degrees C vs 37.3 (SEM 0.2) degrees C, P less than 0.01], a lower final Tsk [20.7 (SEM 0.4) degrees C vs 21.2 (SEM 0.3) degrees C, P less than 0.01] with no change in metabolic heat production. These observations are indicative of an hypothermic insulative isometabolic general cold adaptation, which was associated with a local cold adaptation of the extremities, as shown by warmer foot temperatures [12.3 (SEM 0.9) degrees C vs 9.8 (SEM 0.9) degrees C, P less than 0.001].     

Ontogeny of deep-body cold sensitivity in Pekin ducklings Anas platyrhynchos

The ontogeny of deep-body cold sensitivity was studied in 1 to 12 days old Pekin ducklings Anas platyrhynchos. Deep-body cold sensitivity was determined by means of thermodes implanted in the abdominal cavity. The thermodes were perfused with cold water for 15-min periods to lower the core temperature. Cooling of the body core elicited increases in metabolic rate and vasoconstrictions in the legs of all the ducklings. From the changes induced in metabolic rate and core temperature, deep-body cold sensitivity values of between −5.17 and −6.36 W · kg⁻¹ · °C⁻¹, were estimated. These values, which are in the range of those reported previously for adult Pekin ducks, did not change with age, and it is concluded that deep-body cold sensitivity is fully developed at hatching. Our next aim was to investigate whether the autonomic responses elicited by exposure of ducklings to cold ambient conditions could be explained by temperature changes within the body core. During cold exposure, the increase in metabolic rate was not accompanied by a concomitant decrease in core temperature. On the contrary, deep-body temperature increased slightly during the initial phase of cold exposure. The ducklings attained a metabolic rate amounting to 85–90% of their peak metabolic rate before the core temperature fell below the regulated level measured at thermoneutrality. Thus, despite the findings that Pekin ducklings have a highly-developed deep-body cold sensitivity, their metabolic cold defence under natural conditions seems to be mediated primarily by peripheral thermoreceptors. Accepted: 7 January 1997     

Cold adaptation of a mesophilic subtilisin-like protease by laboratory evolution

Enzymes isolated from organisms native to cold environments generally exhibit higher catalytic efficiency at low temperatures and greater thermosensitivity than their mesophilic counterparts. In an effort to understand the evolutionary process and the molecular basis of cold adaptation, we have used directed evolution to convert a mesophilic subtilisin-like protease from Bacillus sphaericus, SSII, into its psychrophilic counterpart. A single round of random mutagenesis followed by recombination of improved variants yielded a mutant, P3C9, with a catalytic rate constant (k(cat)) at 10 degrees C 6.6 times and a catalytic efficiency (k(cat)/K(M)) 9.6 times that of wild type. Its half-life at 70 degrees C is 3.3 times less than wild type. Although there is a trend toward decreasing stability during the progression from mesophile to psychrophile, there is not a strict correlation between decreasing stability and increasing low temperature activity. A first generation mutant with a >2-fold increase in k(cat) is actually more stable than wild type. This suggests that the ultimate decrease in stability may be due to random drift rather than a physical incompatibility between low temperature activity and high temperature stability. SSII shares 77. 4% identity with the naturally psychrophilic protease subtilisin S41. Although SSII and S41 differ at 85 positions, four amino acid substitutions were sufficient to generate an SSII whose low temperature activity is greater than that of S41. That none of the four are found in S41 indicates that there are multiple routes to cold adaptation.     

Disentangling environmental drivers of metabolic flexibility in birds: the importance of temperature extremes versus temperature variability

Examining physiological traits across large spatial scales can shed light on the environmental factors driving physiological variation. For endotherms, flexibility in aerobic metabolism is especially important for coping with thermally challenging environments and recent research has shown that aerobic metabolic scope [the difference between maximum thermogenic capacity (M_sum) and basal metabolic rate (BMR)] increases with latitude in mammals. One explanation for this pattern is the climatic variability hypothesis, which predicts that flexibility in aerobic metabolism should increase as a function of local temperature variability. An alternative explanation is the cold adaptation hypothesis, which predicts that cold temperature extremes may also be an important driver of variation in metabolic scope. To determine the thermal drivers of aerobic metabolic flexibility in birds, we combined data on metabolic scope from 40 bird species sampled across a range of environments with several indices of local ambient temperature. Using phylogenetically‐informed analyses, we found that minimum winter temperature was the best predictor of variation in avian metabolic scope, outperforming all other thermal variables. Additionally, M_sum was a better predictor of latitudinal patterns of metabolic scope than BMR, with species inhabiting colder environments exhibiting increased M_sum over their counterparts in warmer environments. Taken together, these results suggest that cold temperature extremes drive latitudinal patterns of metabolic scope via selection for enhanced thermogenic performance in cold environments, supporting the cold adaptation hypothesis. Temperature extremes may therefore be an important selective pressure driving macrophysiological trends of aerobic performance in endotherms.     

Involvement of basal metabolic rate in determination of type of cold tolerance

This study aimed to assess the relationship between basal metabolic rate (BMR) and metabolic heat production, and to clarify the involvement of BMR in determining the phenotype of cold tolerance. Measurements of BMR, maximum oxygen uptake, and cold exposure test were conducted on ten males. In the cold exposure test, rectal (T(rec)) and mean skin temperatures (T(ms)), oxygen uptake, and blood flow at forearm (BF(arm)) were measured during exposure to cold (10 degrees C) for 90 min. Significant correlations were observed between BMR and increasing rate of oxygen uptake, as well as between decreasing rate of BF(arm) and increasing rate of oxygen uptake at the end of cold exposure. These findings suggested that individuals with a lower BMR were required to increase their metabolic heat production during cold exposure, and that those with a higher BMR were able to moderate increased metabolic heat production during cold exposure because they were able to reduce heat loss. This study showed that BMR is an important factor in determining the phenotype of cold tolerance, and that individuals with a low BMR showed calorigenic-type cold adaptation, whereas subjects with a high BMR exhibited adiabatic-type cold adaptation by peripheral vasoconstriction.     

Diurnal variation of heat intake in ovariectomized, steroid-treated rats

Ovariectomized rats trained to work for radiant heat reward in a cold environment were implanted with subcutaneous Silastic capsules containing either estradiol, progesterone, both estradiol and progesterone, or no hormone. The hormone treatments produced an average plasma estradiol concentration of 41 pg/ml and progesterone concentration of 20–50 ng/ml. All groups obtained more heat behaviorally when tested during the light phase of the LD cycle than when tested in the dark. Body temperatures and metabolic rates were higher during the night than during the day. There were no differences between groups in behavioral heat intake or body temperature. All hormone-treated groups showed a greater reduction in core temperature than the control group when an exogenous source of heat was not available, but there was no substantial effect of the hormone treatments on metabolic rate except for a 6–7% increase in metabolism of the estrogen group. The increased cooling rate of all hormone-treated groups may indicate a nonspecific steroid-induced increase in heat loss in the cold. The diurnal variation in heat intake establishes the LD cycle as a significant variable in thermoregulatory behavior of the rat. Thus, behavioral heat intake is high during the day when metabolism and body temperature are low, and low at night when metabolism and body temperature are high in this nocturnal species.     

Influence of cooling temperature and duration on cold adaptation of Lactobacillus acidophilus RD758

The effect of different cooling temperatures and durations on resistance to freezing and to frozen storage at -20 degrees C in Lactobacillus acidophilus RD758 was studied, by using a central composite rotatable design. A cold adaptation was observed when the cells were maintained at moderate temperature (26 degrees C) for a long time (8h) before being cooled to the final temperature of 15 degrees C. These conditions led to a low rate of loss in acidification activity during frozen storage (0.64 minday(-1)) and a high residual acidification activity after 180 days of frozen storage (1011 min). The experimental design allowed us to determine optimal cooling conditions, which were established at 28 degrees C during 8h. Adaptation to cold temperatures was related to an increase in the unsaturated to saturated fatty acid ratio and in the relative cycC19:0 fatty acid concentration. Moreover, an increased synthesis of four specific proteins was observed as an adaptive response to the optimal cooling conditions. They included the stress protein ATP-dependent ClpP and two cold induced proteins: pyruvate kinase and a putative glycoprotein endopeptidase.     

Effects of age, sex, and physical fitness on responses to local cooling

The response to local cooling was estimated by the cold hand test (5 degrees C for 2 min) and the cold face test (0 degrees C with 66 km.h-1 wind for 2 min). Heart rate, blood pressure, and skin temperature were measured before, during, and after the tests. The increase in blood pressure (cold hand test) and the fall in Tsk (cold face test) were reduced in trained subjects. Similarly older subjects (53-60 yr of age) responded less to a cold hand test than younger subjects aged 20-40. However, the bradycardia caused by the cold face test was more pronounced in the older subjects. The responses to the cold hand and cold face tests were the same for male and female subjects. During the 2 min after the test, blood pressure and heart rate fell below initial values in the female group but not in the male. It is concluded that, besides adaptation to cold, individual factors such as age, sex, and physical fitness also have a relative importance in the responses to local cooling.     

Rheological modelling of physiological variables during temperature variations at rest

The evolution with time of cardio-respiratory variables, blood pressure and body temperature has been studied on six males, resting in semi-nude conditions during short (30 min) cold stress exposure (0°C) and during passive recovery (60 min) at 20°C. Passive cold exposure does not induce a change inHR but increasesVO ₂,VCO ₂ Ve and core temperatureT _re, whereas peripheral temperature is significantly lowered. The kinetic evolution of the studied variables was investigated using a Kelvin-Voigt rheological model. The results suggest that the human body, and by extension the measured physiological variables of its functioning, does not react as a perfect viscoelastic system. Cold exposure induces a more rapid adaptation for heart rate, blood pressure and skin temperatures than that observed during the rewarming period (20°C), whereas respiratory adjustments show an opposite evolution. During the cooling period of the experiment the adaptative mechanisms, taking effect to preserve core homeothermy and to obtain a higher oxygen supply, increase the energy loss of the body.