Hypothalamic mechanisms in thermoregulation

Certain preoptic and rostral hypothalamic neurons are sensitive to changes in local preoptic temperature (Tpo). These neurons also receive much afferent input from peripheral thermoreceptors and control a variety of thermoregulatory responses. In thermode-implanted animals, preoptic warming increases the firing rate in warm-sensitive neurons and elicits heat loss responses such as panting and sweating. Preoptic cooling increases the firing rate in cold-sensitive neurons and elicits, first, heat retention responses (e.g., cutaneous vasoconstriction and thermoregulatory behavior), then heat production responses (e.g., shivering and nonshivering thermogenesis). It is likely that the preoptic thermosensitive neurons control these thermoregulatory responses because both respond similarly to changes in Tpo and skin temperature. Specifically, skin warming not only increases panting, skin blood flow, and the firing rate of warm-sensitive neurons, but also decreases the sensitivity of all these responses to Tpo changes. Skin cooling not only increases metabolic heat production, heat retention behavior, and the firing rate of cold-sensitive neurons, but also increases the hypothalamic thermosensitivity of all these responses. Low-firing warm-sensitive neurons receive little afferent input and are most sensitive to high Tpo. Many of these low-firing neurons probably serve in controlling heat loss responses. High-firing warm-sensitive neurons receive much excitatory afferent input and are usually sensitive only to low Tpo. These neurons probably exert their greatest influence on heat production responses, possibly by inhibiting and, thus, determining the thermosensitive characteristics of nearby cold-sensitive neurons.     

Characteristics of thermo-mechanosensitive receptors in human and animal skin

With local thermal and mechanical stimulation in precise experiments on cats, a study was made of changes in impulse activity of afferent fibers of spinal dorsal roots connected with skin thermoreceptors in the extremities. Psychophysiological studies were done on the characteristics of thermosensitive points of the skin of the upper extremities of man. According to changes in average frequency of impulse activity, dynamic sensitivity, latent period of reaction, and thresholds of temperature and mechanical sensitivity, three groups of heat receptors and two of cold receptors were identified in the skin of the cat. All heat and cold receptors are mechanosensitive. According to quality and intensity of perceptions elicited by thermal stimulation and thresholds of sensitivity to mechanical and temperature effects, thermosensitive points in human skin can also be divided into three groups of heat receptors and two groups of cold receptors. All heat and cold points are mechanosensitive. An analogy between the skin thermoreceptors of animals and man is suggested.Institute of Physiology, Kazakhstan, Academy of Sciences. Translated from Neirofiziologiya, Vol. 24, No. 3, pp. 314–322, May–June, 1992.     

Thermophysiological consequences of whole body resonant RF exposure (100 MHz) in human volunteers

Thermophysiological responses of heat production and heat loss were measured in seven adult volunteers (six males and one female, aged 31-74 years) during 45 min dorsal exposures of the whole body to 100 MHz continuous wave (CW) radio frequency (RF) energy. Three power densities (PD) (average PD = 4, 6, and 8 mW/cm(2); whole body specific absorption rate [SAR] = 0.068 [W/kg]/[mW/cm(2)]) were tested in each of three ambient temperatures (T(a) = 24, 28, and 31 degrees C), as well as in T(a) controls (no RF). A standardized protocol (30 min baseline, 45 min RF or sham exposure, 10 min baseline) was used. Measured responses included esophageal and seven skin temperatures, metabolic heat production, local sweat rate, and local skin blood flow. No changes in metabolic heat production occurred under any test condition. Unlike published results of similar exposures at 450 and 2450 MHz, local skin temperatures, even those on the back that were irradiated directly, changed little or not at all during 100 MHz exposures. The sole exception was the temperature of the ankle skin, which increased by 3-4 degrees C in some subjects at PD = 8 mW/cm(2). During the 45 min RF exposure, esophageal temperature showed modest changes (range = -0.15 to 0.13 degrees C) and never exceeded 37.2 degrees C. Thermoregulation was principally controlled by appropriate increases in evaporative heat loss (sweating) and, to a lesser extent, by changes in skin blood flow. Because of the deep penetration of RF energy at this frequency, effectively bypassing the skin, these changes must have been stimulated by thermal receptors deep in the body rather than those located in the skin.     

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.     

Partial-body exposure of human volunteers to 2450 MHz pulsed or CW fields provokes similar thermoregulatory responses

Many reports describe data showing that continuous wave (CW) and pulsed (PW) radiofrequency (RF) fields, at the same frequency and average power density (PD), yield similar response changes in the exposed organism. During whole-body exposure of squirrel monkeys at 2450 MHz CW and PW fields, heat production and heat loss responses were nearly identical. To explore this question in humans, we exposed two different groups of volunteers to 2450 MHz CW (two females, five males) and PW (65 micros pulse width, 10(4) pps; three females, three males) RF fields. We measured thermophysiological responses of heat production and heat loss (esophageal and six skin temperatures, metabolic heat production, local skin blood flow, and local sweat rate) under a standardized protocol (30 min baseline, 45 min RF or sham exposure, 10 min baseline), conducted in three ambient temperatures (T(a) = 24, 28, and 31 degrees C). At each T(a), average PDs studied were 0, 27, and 35 mW/cm2 (Specific absorption rate (SAR) = 0, 5.94, and 7.7 W/kg). Mean data for each group showed minimal changes in core temperature and metabolic heat production for all test conditions and no reliable differences between CW and PW exposure. Local skin temperatures showed similar trends for CW and PW exposure that were PD-dependent; only the skin temperature of the upper back (facing the antenna) showed a reliably greater increase (P =.005) during PW exposure than during CW exposure. Local sweat rate and skin blood flow were both T(a)- and PD-dependent and showed greater variability than other measures between CW and PW exposures; this variability was attributable primarily to the characteristics of the two subject groups. With one noted exception, no clear evidence for a differential response to CW and PW fields was found.     

Prediction of the thermoregulatory response for clothed immersion in cold water

A multi-compartmental thermoregulatory model was applied to data of ten resting clothed males immersed for 3 h in water at 10 and 15 degrees C. Clothing consisted of a dry suit and either a light or heavy undergarment, representing a total insulation of 0.15 (0.95) or 0.20 m2 degrees CW-1 (1.28 clo), respectively. Data were grouped according to low (less than 14%) and high (14 to 24%) body fat individuals. Mean decreases in rectal temperature ranged from 0.79 to 1.38 degrees C, mean decreases in the mean weighted skin temperature ranged from 6.3 to 10.2 degrees C, and mean increases in the metabolic rate ranged from 33.9 to 80.8 W. The model consists of eight segments, each representing a specific region of the body. Each segment is comprised of compartments representing the core, muscle, fat, skin, and clothing. Each compartment is assigned thermophysical values of heat conduction and heat capacitance, and with the exception of clothing, physiological values of blood flow and metabolic heat production. During cold exposure, responses are directed towards increased heat production in the form of shivering and heat conservation in the form of vasoconstriction and convective heat exchange at the vascular level. Agreement between the model predictions and the experimental observations was obtained by adjusting the parameters governing these responses.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neuropeptide Y acts directly in the periphery on fat tissue and mediates stress-induced obesity and metabolic syndrome

The relationship between stress and obesity remains elusive. In response to stress, some people lose weight, whereas others gain. Here we report that stress exaggerates diet-induced obesity through a peripheral mechanism in the abdominal white adipose tissue that is mediated by neuropeptide Y (NPY). Stressors such as exposure to cold or aggression lead to the release of NPY from sympathetic nerves, which in turn upregulates NPY and its Y2 receptors (NPY2R) in a glucocorticoid-dependent manner in the abdominal fat. This positive feedback response by NPY leads to the growth of abdominal fat. Release of NPY and activation of NPY2R stimulates fat angiogenesis, macrophage infiltration, and the proliferation and differentiation of new adipocytes, resulting in abdominal obesity and a metabolic syndrome-like condition. NPY, like stress, stimulates mouse and human fat growth, whereas pharmacological inhibition or fat-targeted knockdown of NPY2R is anti-angiogenic and anti-adipogenic, while reducing abdominal obesity and metabolic abnormalities. Thus, manipulations of NPY2R activity within fat tissue offer new ways to remodel fat and treat obesity and metabolic syndrome.     

Temperature distribution in human skin and subdermal tissues

Temperature profiles have been computed in the skin and subdermal part of a human body for (i) various values of environmental temperature, rate of sweat evaporation and wind velocity, (ii) rate of blood mass flow, (iii) rate of metabolic heat generation and (iv) three different sets of thicknesses of skin layers. The mathematical equations have been considered for a one-dimensional steady-state case. The two important physical parameters, namely rate of blood mass flow and rate of metabolic heat generation, have been assigned position-dependent values. The latter is also taken as linearly dependent on the tissue temperature. Analytic solutions have been obtained for the three layers of the region. These forms of solution facilitate the study of parameter dependence.     

Blood flow and muscle bio-energetics by 31P-nuclear magnetic resonance after local cold acclimation.

To clarify the origin of local cold adaptation and to define precisely its influence on muscle bio-energetics during local exercise, five subjects were subjected to repeated 5 degrees C cold water immersion of the right hand and forearm. The first aim of our investigation was therefore carried out by measuring local skin temperatures and peripheral blood flow during a cold hand test (5 degrees C, 5 min) followed by a 10-min recovery period. The 31P by nuclear magnetic resonance (31PNMR) muscle bio-energetic changes, indicating possible heat production changes, were measured during the recovery period. The second aim of our investigation was carried out by measuring 31PNMR muscle bioenergetics during handgrip exercise (10% of the maximal voluntary contraction for 5 min followed by a 10-min recovery period) performed both at a comfortable ambient temperature (22 degrees C; E) and after a cold hand test (EC), before and after local cold adaptation. Local cold adaptation, confirmed by warmer skin temperatures of the extremities (+30%, P less than 0.05), was related more to an increased peripheral blood flow, as shown by the smaller decrease in systolic peak [-245 (SEM 30) Hz vs -382 (SEM 95) Hz, P less than 0.05] than to a change in local heat production, because muscle bioenergetics did not vary. Acute local cold immersion decreased the inorganic phosphate:phosphocreatine (PC) ratio during EC compared to E [+0.006 (SEM 0.010) vs +0.078 (SEM 0.002) before acclimation and +0.029 (SEM 0.002) vs +0.090 (SEM 0.002) after acclimation respectively, P less than 0.05] without significant change in the PC:beta-adenosine triphosphate ratio and pH. Local adaptation did not modify these results statistically. The recovery of PC during E increased after acclimation [9.0 (SEM 0.2) min vs 3.0 (SEM 0.4) min, P less than 0.05]. These results suggested that local cold adaptation is related more to peripheral blood flow changes than to increased metabolic heat production in the muscle.     

Prediction of temperature profiles in the human skin and subcutaneous tissues

Exact mathematical solutions in terms of confluent hypergeometric and Airy's functions are obtained to study the steady state temperature distributions in human skin and subcutaneous tissues (SST). It is assumed that the skin is exposed to an air environment and heat transfer from the skin occurs by convection, radiation and evaporation. A mathematical model of the SST, accounting for heat conduction, perfusion of the capillary beds and metabolic heat productions of the dermis and subcutaneous tissues, has been solved to obtain interface temperatures for a wide range of environmental temperatures, rates of evaporation of sweat, wind speeds and relative humidities. The solutions provide inter-relationships between interface temperatures, thermal conductivities, metabolic heat production, blood perfusion, thicknesses of various layers of SST and ambient temperature.     

Control of sweating in man after work-induced thermal load and symmetrically applied cooling

To examine the compensatory effects of work-induced thermal load and symmetrically applied local cooling on local sweat rates, two kinds of experiment were carried out on eight male subjects in a climatic chamber: 1) Experiments at 36 degrees C ambient temperature with a work load of about 25 W by the right leg. 2) Experiments at 36 degrees C ambient temperature with a work load of about 25 W by the right leg as in 1., but with additional compensatory cooling of the left leg controlled throughout by heat balance calculations at 75-85 W, equal to the heat produced in the working leg, the necessary air temperature being dependent on local sweat rate. Work load without cooling brought about a significant increase in core temperatures, metabolism, heart rate and local sweat rates. With unchanged local skin temperatures local sweat rate increase was higher in the working leg. Therefore the existence of muscle thermoreceptors should be assumed, the afferent information from which is processed and weighted in a different way to that provided by skin receptors. Work load combined with additional cooling reduced local and mean skin temperatures and heart rate, but had no significant influence on core temperature or metabolism. However, local sweat rate was generally lower in both thighs, with a major reduction in the cooled leg confirming control of local sweat rate by local temperature.(ABSTRACT TRUNCATED AT 250 WORDS)     

The relative influence of physical fitness, acclimatization state, anthropometric measures and gender on individual reactions to heat stress

An experiment was set up to quantify the relative influence of fitness, acclimatization, gender and anthropometric measures on physiological responses to heat stress. For this purpose, 12 male and 12 female subjects were exposed to a neutral [ambient temperature (Ta) 21 degrees C, relative humidity (r.h. 50%)], a warm, humid (Ta 34 degrees C, r.h. 80%) and a hot, dry (Ta 45 degrees C, r.h. 20%) climate at rest and at two exercise intensities [25%, and 45% maximal O2 intake (VO2max)], seated seminude in a net chair behind a cycle ergometer. Their physiological responses were recorded and the data submitted to a multiple regression analysis. It was shown that for the variance in heat storage, the percentage of body fat and the surface to mass ratio had relatively the largest influence of all the individual parameters, followed by VO2max and the sweat rate versus increase in core temperature (total r2 = 92%). For the skin temperature variation, the relative influence of individual parameters (sweat gain, VO2max) was small. For body core temperatures, individual parameters had a large influence. The largest effect was due to the percentage of fat and the surface to mass ratio, followed by the sweating setpoint and, finally, VO2max (total r2 = 54%-70%). For the variance in heart rate the VO2max was the most relevant parameter, followed by the setpoint of the sweat rate:rectal temperature relationship (total r2 = 88%). Blood pressure and skin blood flow predictions were also shown to improve by the addition of individual characteristics to the model.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of blood flow,curved boundary and environmental conditions on temperature distribution in a two dimensional model of human skin and subcutaneous tissues

A mathematical model for the study of the effects of blood flow, metabolic heat production, various environmental conditions and the presence of a curved boundary on the temperature distribution (TD) in a two dimensional model of human skin and subcutaneous tissues (SST) is presented. Based on physiological properties, the interfaces between epidermis-dermis (IED) and dermis-subcutaneous tissues (IDS) have been considered to be irregular and the regions of these layers have been divided into 109 triangular elements of various sizes which are connected with each other by 70 nodes. The results computed from this thermobiological mathematical model, using Galerkin's finite element technique, have been exhibited graphically. The effects of various environmental conditions, blood flow and metabolic heat production are found to be nonuniform on TD at the nodes situated at the same depth in SST. This nonuniformity in TD almost disappears at the nodes situated in dermis nearest to IDS except for the two of the six combinations, considered in the present study, in which highest values of blood flow and metabolic heat production have been considered. The rate of fall of temperature with respect to thickness (towards the skin surface) is higher at the straight boundary (SB) than at the curved boundary (CB). The temperature increases with respect to width (from SB to CB) in epidermis and dermis but decreases in subcutaneous tissues. This increase or decrease of temperature is more pronounced at the nodes situated near to, or at CB. The trend of these temperature profiles in SST reflects the dependence of TD not only on the environmental conditions and biophysical variables but also on the geometry of SST.     

Shivering onset, metabolic response, and convective heat transfer during cold air exposure

The onset and intensity of shivering of various muscles during cold air exposure are quantified and related to increases in metabolic rate and convective heat loss. Thirteen male subjects resting in a supine position and wearing only shorts were exposed to 10 degrees C air (42% relative humidity and less than 0.4 m/s airflow) for 2 h. Measurements included surface electromyogram recordings at six muscle sites representing the trunk and limb regions of one side of the body, temperatures and heat fluxes at the same contralateral sites, and metabolic rate. The subjects were grouped according to lean (LEAN, n = 6) and average body fat (NORM, n = 7) content. While the rectal temperatures fluctuated slightly but not significantly during exposure, the skin temperature decreased greatly, more at the limb sites than at the trunk sites. Muscles of the trunk region began to shiver sooner and at a higher intensity than those of the limbs. The intensity of shivering and its increase over time of exposure were consistent with the increase in the convective heat transfer coefficient calculated from skin temperatures and heat fluxes. Both the onset of shivering and the magnitude of the increase in metabolic rate due to shivering were higher for the LEAN group than for the NORM group. A regression analysis indicates that, for a given decrease in mean skin temperature, the increase in metabolic rate due to shivering is attenuated by the square root of percent body fat. Thus the LEAN group shivered at higher intensity, resulting in higher increases in metabolic heat production and convective heat loss during cold air exposure than did the NORM group.     

Active cutaneous vasodilation in resting humans during mild heat stress.

The role of skin temperature in reflex control of the active cutaneous vasodilator system was examined in six subjects during mild graded heat stress imposed by perfusing water at 34, 36, 38, and 40 degrees C through a tube-lined garment. Skin sympathetic nerve activity (SSNA) was recorded from the peroneal nerve with microneurography. While monitoring esophageal, mean skin, and local skin temperatures, we recorded skin blood flow at bretylium-treated and untreated skin sites by using laser-Doppler velocimetry and local sweat rate by using capacitance hygrometry on the dorsal foot. Cutaneous vascular conductance (CVC) was calculated by dividing skin blood flow by mean arterial pressure. Mild heat stress increased mean skin temperature by 0.2 or 0.3 degrees C every stage, but esophageal and local skin temperature did not change during the first three stages. CVC at the bretylium tosylate-treated site (CVC(BT)) and sweat expulsion number increased at 38 and 40 degrees C compared with 34 degrees C (P < 0.05); however, CVC at the untreated site did not change. SSNA increased at 40 degrees C (P < 0.05, different from 34 degrees C). However, SSNA burst amplitude increased (P < 0.05), whereas SSNA burst duration decreased (P < 0.05), at the same time as we observed the increase in CVC(BT) and sweat expulsion number. These data support the hypothesis that the active vasodilator system is activated by changes in mean skin temperature, even at normal core temperature, and illustrate the intricate competition between active vasodilator and the vasoconstrictor system for control of skin blood flow during mild heat stress.     

Temperature regulation during rest and exercise in the cold in premenarcheal and menarcheal girls.

Temperature regulation during exercise in the cold was examined in 13 adolescent female individuals, aged 13-18 yr. Six girls with established menstrual cycles comprised the eumenorrheic menarcheal (EM) group, and seven nonmenstruating girls comprised the premenarcheal (PM) group. During the first visit, maximal oxygen consumption (Vo(2 max)), height, weight, and percent body fat were measured. The second visit included a determination of metabolic rate in thermoneutrality (21 degrees C), consisting of a 10-min rest period and 20 min of cycling (30% of Vo(2 max)), and a cold test (5 degrees C, 40% humidity, <0.3 m/s air velocity) involving a 20-min rest period and 40 min of cycling (30% of Vo(2 max)). Subjects in the EM group were tested twice in the chamber: once during the follicular and once during the luteal phase. Heat production per kilogram in thermoneutrality and in the cold was significantly (P < 0.05) higher in the PM compared with the EM girls. However, the PM girls had a significantly (P < 0.05) lower core temperature in the cold than the EM group. PM girls also had a significantly higher body surface area-to-mass ratio compared with the EM girls. Although percent body fat between groups was not significantly different, within the PM group percent body fat explained 79% (P < 0.01) of the variance in the decrease of core temperature. There were no menstrual phase-related differences in temperature regulation in either the thermoneutral or cold environment. In conclusion, menstrual phase does not influence temperature regulation in female individuals during adolescence. EM girls had lower metabolic heat production but maintained their core temperature more effectively in the cold than did the PM girls. This thermoregulatory difference between PM and EM girls is mainly a function of geometric differences with maturation-related peripheral vasoconstrictive differences maybe limiting the effectiveness of the mechanism of increased heat storage in younger female individuals.     

Dynamic effects of acute cooling in body temperature regulation of the euthermic warm-acclimated golden hamster (Mesocricetus auratus)

During the dynamic phase of external cooling of euthermic golden hamsters in the initial period of metabolic response, peripheral body temperature is the decisive control variable determining the level of metabolic heat production. Under these conditions the rate as well as the magnitude of the peripheral body temperature change constitute the effectual input to the controller of body temperature. The apparent sensitivity with which the regulator drives the metabolic response to unit change of the peripheral temperature is in an inverse relation to the rate of peripheral temperature change. This parameter, despite its limited significance can serve as a working index characterising the thermoregulatory system in different groups of experimental animals of the same species providing that the actual conditions of the experiment are comporting.     

Effect of alterations in ambient temperature on blood flow in the skin.

The effect of changing ambient temperature on skin temperature was recorded in human subjects; also, its effect on blood flow was measured using venous occlusion and optical plethysmography. When cold stimulus was removed in stages using a heating cabinet, it was found that a biphasic flow response occurred in the fingers with each step change in temperature. There was a rapid transient rise followed by a decline to an equilibrium flow level. The transient rise occurred even when the temperature rose from 37 to 40 degrees C, although at this level the equilibrium remained unchanged. It is suggested that the transient rise was due to stimulation of Hensel's dynamic warmth receptors, whereas the rise in equilibrium temperature was due to removal of cold stimulus, which at low ambient temperatures maintains reflex vasoconstriction through activation of static cold receptors. Upper arm skin responded to removal of cold stimulus by a fall in temperature. Immersion of a different limb in cold water produced vasoconstriction in fingers but vasodilatation in the upper arm skin. It is suggested that this may be due to neurogenic vasodilatation, though the present work gives no indication as to pathways.     

Dynamic changes in sweat rates and evaporation rates through clothing during hot exposure

Dynamic changes in local sweat rates (S_w) and local evaporation rates from clothing (E_cl) have been observed during hot exposure. Four young male subjects wearing a cotton T-shirt and half shorts were exposed to 40 °C/50% for 1 h following exposure to 28 °C/50% for 30 min. Amount of water absorbed in clothing (M_sw), clothing surface temperatures (T_cl), local heat flow rates, skin temperatures, body weight, rectal temperature, S_w and E_cl were continuously measured. Upon exposure to the heat, decrease in heat gain to the skin was observed as opposed to increase in S_w, E_cl, M_sw and heat gain to the clothing surface.