INTRODUCTION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

BOTH CORE TEMPERATURES (T_c) and skin temperatures (T_sk) have afferent input to the thermoregulatory system, and it is generally accepted that changes in T_c are more heavily weighted than changes in T_sk in triggering autonomic responses that maintain thermal homeostasis (29). For example, in the goat, the T_c/T_sk contribution ratio for metabolic heat production is 3:1 (19). Human studies report T_c/T_sk contribution ratios between 6:1 and 20:1 for the sweating response (24, 32) and between 3:1 and 5:1 for metabolic heat production (8, 23). Although the greater contribution from T_c is recognized for the autonomic thermoregulatory responses, the relative importance of T_c and T_sk as determinants of thermal comfort remains to be determined. Thermal comfort is responsible for the initiation of behavioral thermoregulation (31) and is, therefore, of great significance in humans, who are able to carefully control both ambient temperature and level of body-surface insulation.

Although animal studies do allow some behavioral responses to be measured (e.g., ambient temperature-seeking behavior) (6), thermal sensation or comfort is difficult to assess. In the squirrel monkey, T_c and T_sk contribute in the same direction for behavioral and autonomic thermoregulatory responses (30), and there is core and cutaneous interaction for behavior (1), but the T_c/T_sk ratio of contribution has not been determined. To preserve body temperature homeostasis during environmental thermal challenges, it would be advantageous to have T_sk more heavily weighted relative to T_c as a contributor to thermal comfort. This would allow the behavioral response to precede more energetically costly responses, such as vasoconstriction and shivering.

The aim in this study was to determine the T_c/T_sk contribution ratio for thermal comfort in humans and to compare this ratio to those for autonomic thermoregulatory responses. T_c and T_sk were independently altered while thermal comfort and the autonomic and metabolic thermoregulatory responses were assessed. Because of the high efficiency and low energy cost of behavioral strategies that humans use in thermoregulation, we hypothesized that the skin surface is more heavily weighted as a determinant of subjective thermal comfort than for the autonomic responses that regulate body temperature.

	METHODS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

Subject selection and study design. With approval from the Johns Hopkins Hospital Committee on Clinical Investigation, and after written informed consent was obtained, eight men (ages 22-28 yr) were enrolled as subjects. No subject had cardiovascular, pulmonary, renal, or other significant disease, and none was taking any medication. An estimate of percent body fat was made by the infrared interactance method over the biceps skinfold (Futrex, Hagerstown, MD) (9). All studies were performed in the Johns Hopkins Hospital Outpatient Clinical Research Center between the hours of 8:00 and 11:00 AM. Ambient temperature averaged 23.2 ± 0.8°C, and relative humidity was ~60%. Subjects were dressed in a thin cotton gown and were allowed to rest comfortably in the supine position with the head elevated ~30°.

Temperature monitoring. T_c was monitored at the tympanic membrane by using thermocouple probes (Mallinckrodt Medical, St. Louis, MO). The probes were inserted until an audible scratching sound was reported by the subject; thus placement against the tympanic membrane was assured. The external auditory canal was then packed with cotton for insulation. Skin-surface thermocouples (Mallinckrodt) were placed at 10 sites to allow calculation of a weighted average mean T_sk, which was defined as 0.06 · forehead + 0.09 · upper arm + 0.06 · forearm + 0.045 · hand + 0.19 · back + 0.095 · chest + 0.095 · abdomen + 0.19 · thigh + 0.115 · calf + 0.06 · foot (22). All thermocouples were linked to an electronic thermometer (Iso-thermex, Columbus Instruments, Columbus, OH), and temperatures were recorded at 5-min intervals throughout the study by using a laptop computer. Precision and accuracy with this thermometry system are to 0.01 and 0.1°C, respectively. Before this series of experiments, the thermometry system was calibrated against a standard mercury-in-glass thermometer.

Thermal comfort. Subjective thermal comfort was assessed by using a 10-point scale (with 0 = "the coldest you've ever been;" 5 = "neutral, neither cold nor warm;" and 10 = "the hottest you've ever been.") These data were collected at 5-min intervals throughout the studies by using a visual analog scale.

Thermoregulatory responses. Vasomotor tone was measured by using laser Doppler flowmetry (Perimed-PF4, Stockholm, Sweden) over the tip of the index finger of the left upper extremity; data were recorded onto a hard disk every 1 s. Blood flow data (in laser Doppler perfusion units) were analyzed as a running average of 1-min epochs. At every 5-min interval, a 1-min average was used as a quantitative measure of blood flow. Metabolic heat production was determined by measuring total body oxygen consumption (ml/min) by indirect calorimetry (Deltatrac, Sensormedics, Anaheim, CA). These data were recorded at 5-min intervals. Shivering was assessed with a four-point scale where 0 = no shivering, 1 = occasional mild tremors of the jaw and neck, 2 = intensive tremors of the chest, 3 = intermittent vigorous generalized tremor, and 4 = continuous violent muscle activity.

Catecholamine measurements. Plasma concentrations of norepinephrine and epinephrine were measured in mixed venous blood drawn through the long-arm intravenous catheter after 10 ml of fluid were discarded to ensure undiluted sampling. Samples were drawn at baseline (before T_sk or T_c manipulations), at 15-min intervals during the T_sk treatment phase, and at every 0.5°C increment of T_c during the core-cooling phase (36.5, 36.0, and 35.5°C). Specimens were temporarily stored on ice in tubes that contained EDTA. The plasma was then separated in a refrigerated centrifuge and was stored at 80°C. Catecholamine concentrations were measured by using high-pressure liquid chromatography, with electrochemical detection after alumina extraction. The sensitivity of this assay is ~5 pg/ml, and the intra- and interassay coefficients of variation are <5%.

Data analysis. Multiple linear regression was performed for each measured response (thermal comfort, vasomotor tone, metabolic heat production, norepinephrine, and epinephrine) in each individual subject, where where y is measured response, a is T_c regression coefficient, b is T_sk regression coefficient, and c is regression intercept.

	RESULTS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

All the subjects were nonobese men, ages 22-28 yr (Table 1). The primary measured outcomes are reported for the two phases of the study (Fig. 1). The first phase is the T_sk treatment, and the second phase is the T_c treatment.

View larger version (35K): [in this window] [in a new window]   Fig. 1.   Core temperature (Core temp), mean skin-surface temperature (Mean skin temp), fingertip blood flow (Blood Flow), total body O2 consumption (O2), norepinephrine (Norepi), epinephrine (Epi), and thermal conmfort scores in 8 human subjects who were studied on 3 separate days. , Cold-skin day; , neutral-skin-temperature day; , warm-skin day. Mean skin temperature was achieved by mattresses with circulating water applied between minutes 15 and 120. Core temperature was independently decreased between minutes 75 and 120 by infusion of cold (4°C) saline (40 ml/kg iv). For clarity, symbols for significance are shown at every other time interval. * Significant difference vs. other 2 skin-temperature-treatment groups, P < 0.05. # Significant difference vs. pretreatment baseline for all 3 groups, P < 0.05.

Skin-treatment phase. After a stable baseline was established for 15 min of data collection, T_sk was adjusted to the target temperatures and held constant throughout the study. Mean T_sk was ~30, 34, and 36°C on the cold-, neutral-, and warm-skin-study days, respectively. During the T_sk treatment, baseline fingertip blood flow decreased and plasma norepinephrine concentrations increased on the cold-skin day. As expected subjective thermal comfort decreased on the cold-skin day and increased on the warm-skin day. Metabolic heat production and plasma epinephrine concentrations remained unchanged from baseline values on all days.

Core-treatment phase. The core cooling phase of the study was accomplished over a 45-min period during which the groups that received cold, neutral, and warm treatments were given 2,990 ± 320, 2,930 ± 300, and 2,940 ± 350 ml of cold intravenous fluid, respectively (P > 0.05 between groups). T_c decreased by a similar magnitude on each treatment day to a nadir of 35.7 ± 0.2, 35.8 ± 0.2, and 35.9 ± 0.2°C in the cold-, neutral-, and warm-skin-treatment groups, respectively (P > 0.05 between groups). Mean T_sk did not change significantly during core cooling. Fingertip blood flow decreased to minimal levels in all three treatment groups during core cooling, indicating near-maximal vasoconstriction. Metabolic heat production was unchanged for the warm-skin-treatment group, but it increased approximately twofold and threefold for the neutral- and cold-skin-treatment groups, respectively. During core cooling, norepinephrine concentrations increased twofold and fourfold on the neutral- and cold-skin-treatment days, respectively, but the norepinephrine concentration was unchanged on the warm-skin day. Epinephrine concentrations increased threefold during core cooling on the cold-skin day, but concentrations were unchanged on the neutral- and warm-skin days. The mean thermal-comfort score decreased during core cooling, but the difference in thermal comfort between skin-treatment groups was maintained. Shivering scores reflected the change in metabolic heat production, and the mean maximal shivering score reached 4 ± 0 on the cold-skin day, 3 ± 1 on the neutral-skin day, and 0 ± 0 on the warm-skin day.

T_c/T_sk contribution. The mean values of the regression coefficients were compared for T_c vs. T_sk for each response to detect differences in the relative contribution of core and skin (Table 2). The T_c regression coefficient was significantly greater than the T_sk coefficient for each autonomic response but not for subjective thermal comfort. For thermal comfort, the T_c/T_sk contribution ratio was ~1:1, but for all other responses the T_c/T_sk ratio was ~2:1 to 4:1 (P < 0.05). The relationships between T_c, T_sk, and the measured responses are shown by simple linear regression in Fig. 2. The slopes of the lines of best fit indicate the gains of the measured responses and thus the relative contributions of T_c and T_sk. For subjective thermal comfort, the slopes were similar for T_c and T_sk. For all other responses (blood flow, metabolic heat production, norepinephrine, and epinephrine), the T_c slope was greater than the T_sk slope; this indicates a greater T_c contribution.

View larger version (39K): [in this window] [in a new window]   Fig. 2.   Linear regressions for core temperature and skin temperature and the measured responses (fingertip blood flow, metabolic heat production, norepinephrine, epinephrine, and subjective thermal comfort score). Data points were taken at 5-min intervals for all 8 study subjects and were combined for each regression. Slope of the line of best fit indicates gain for the measured response. Equations (right column) are derived from multiple linear regression equations. Slope of each measured response (except subjective thermal comfort score) is greater for Tc than for Tsk. For subjective thermal comfort, Tc and Tsk slopes are equal.

	DISCUSSION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

The results support the hypothesis that temperature of the skin surface has a relatively greater contribution to subjective thermal comfort than to the autonomic thermoregulatory responses. T_sk provides input equal to T_c toward thermal comfort, whereas T_sk provides much less input relative to T_c toward the autonomic responses. Given that T_sk changes more rapidly and to a greater extent than does T_c during environmental thermal challenges, the relatively greater contribution of T_sk to thermal comfort serves to initiate behavioral thermoregulation before activation of the more metabolically demanding responses that maintain body temperature.

Previous studies have described the relative contributions of T_c and T_sk to individual thermoregulatory responses but have not quantitatively assessed these inputs as determinants of thermal comfort. Bleichert et al. (5) determined in humans that T_c dominates T_sk in triggering behavioral responses, but these results must be interpreted cautiously since T_c and T_sk were not independently altered in their study of only two subjects. It has been suggested by Chatonnet and Cabanac (7) that perception of cold is derived primarily from T_sk, whereas perception of warm is derived primarily from T_c. This observation was not apparent in the present study, given the relatively linear response for subjective thermal sensation over the whole range of low-to-high temperatures that were achieved. Also, Chatonnet and Cabanac did not independently alter T_c and T_sk.

Both core and cutaneous thermal stimuli are known triggers of behavioral thermoregulatory responses in animals. For instance, Adair (1) allowed squirrel monkeys to alter the air temperature within their chamber. At a T_c (hypothalamic) range of 36-41°C, that was achieved by implanted thermodes, the ambient temperature that the animals selected was linear and inversely proportional to T_c. Changes in ambient temperature initiate nest building, basking, huddling, or postural changes in animals, all with the apparent purpose of regulating body temperature (27). Although much is known about such behavioral responses, the relative contributions of T_c and T_sk to thermal comfort or behavior have not been determined in animals or in humans.

Studies in animals demonstrate the relative predominance of T_c over T_sk as a determinant of the autonomic thermoregulatory responses. Jessen (19) developed a model, in the goat, in which T_c and T_sk were independently controlled. In this model, T_c and T_sk provided linear and independent input for metabolic heat production, with a T_c/T_sk contribution ratio of 3:1, similar to that in the present study. T_sk changes in the range between 25 and 40°C were linearly related to metabolic heat production, whereas T_sk changes below 25°C did not further increase the response. This indicates either that the maximal response had been elicited or that direct muscle cooling decreased metabolic needs (21). In the rat, the T_c/T_sk ratio is great (7:1) for the autonomic thermoregulatory responses (26). Even when cutaneous temperature signals are blocked by denervation, rats maintain a relatively normal response to T_c (hypothalamic) changes (17). In ducks, the T_c/T_sk contribution ratio for metabolic cold defense is between 6:1 and 10:1 (18). In the present study, both T_c and T_sk were altered within the range of temperatures encountered by humans during typical environmental challenges. Unlike the animal studies, our human model allows a more precise measurement of subjective thermal sensation and enables the comparisons of this response to the autonomic responses.

Early studies by Benzinger et al. (4) showed the dominant role of T_c compared with T_sk as a determinant of shivering and metabolic heat production in humans. Subsequently, other human studies have described T_c/T_sk ratios between 3:1 and 5:1 for the metabolic heat-production response during cold challenge. Cheng et al. (8) demonstrated that the proportion of skin contribution is linear over a T_sk range of 31-37°C at T_c temperatures >34.5°C (8), and the T_c/T_sk contribution was 4:1 for both the vasoconstriction and shivering responses. A T_c/T_sk contribution ratio of 2:1 for metabolic heat production is linear when T_sk exceeds 26°C (16). Nadel et al. (24) used radiant heat and exercise to alter T_sk and T_c, respectively, and they demonstrated a contribution of ~7:1 of T_c/T_sk to the sweating response. Crawshaw et al. (10) found the forehead to be more sensitive than other areas (back, leg, chest, and abdomen) to changes in T_sk and the effects on the sweating response. Using ingestion of ice cream or warm pudding to alter T_c, Nadel et al. (25) derived a formula to predict the responses to changing T_sk. At a low T_sk, the metabolic response predominated during decreasing T_c; at a neutral T_sk, the vasomotor response predominated; and at a high T_sk, a reduction in evaporative heat loss occurred. Thermal comfort was not measured during these experiments. Wyss et al. (32) determined that rate of sweating was not influenced by T_sk and was almost exclusively determined by T_c, whereas forearm blood flow (vasodilation) during heat challenge was determined by a 20:1 T_c/T_sk ratio. Although the contribution of T_c and T_sk to the autonomic thermoregulatory responses has been relatively well described, the present study is unique in that a T_c/T_sk contribution ratio was derived for subjective thermal comfort, and this ratio was compared with ratios for other responses. In addition, we measured a T_c/T_sk contribution ratio for plasma catecholamines, which has not been determined previously.

Cold stress can precipitate ischemic cardiac events, including death from myocardial infarction (2). Shivering and the associated increased metabolic demands are a potential mechanism for cardiac morbidity in individuals with limited cardiopulmonary reserve (3). The adrenergic response to core hypothermia (14) increases peripheral vascular tone and arterial blood pressure and can precipitate cardiac morbidity in patients recovering from surgery (11, 12). An important implication of the present study is that, in individuals with core hypothermia, merely warming the skin to achieve thermal comfort may not attenuate the potentially detrimental autonomic responses. For every 1°C of core hypothermia, 1°C of cutaneous warming will provide thermal comfort, but the present results indicate that 3-4°C of cutaneous warming would be required to reverse the adrenergic and metabolic responses. This becomes important, for example, in surgical patients who benefit from aggressive cutaneous warming (12, 13).

On the basis of findings in the present study, the relative importance of T_sk as a determinant of autonomic thermoregulatory responses should not be underestimated. It should be recognized that, despite the lower gain for T_sk compared with T_c, the large change in T_sk that occurs under certain environmental conditions makes it possible for T_sk to be the dominant (or even sole) input responsible for the effector response. Evidence for the importance of T_sk was shown by Savage and Brengelmann (28) in humans, as T_sk was the predominant contributor to changes in forearm blood flow over the relatively narrow thermoneutral zone of T_sk and T_c. Although the regression analysis used in the present study gives relative contribution ratios for T_sk and T_c by using analytical methods, the practical matter is that the skin represents the first line of defense against environmental changes, thus protecting T_c from change.

The following limitations may apply to the present study. The data were analyzed by using the intensity of the individual responses and the slope of the regression for temperature vs. the response. Therefore, we used gain rather than threshold as the primary outcome measure to determine the relative contributions of T_c and T_sk. Because thresholds depend on identification of a slope change in the temperature vs. response curve and are therefore a "dichotomous" response (15), gain seemed a more objective measure than threshold for the purposes of the present study. In addition, gain is impossible to determine for thermal sensation, because there is no clear slope change or initiation of the response. Perhaps another limitation in our study is that we did not attempt to identify dynamic response characteristics by altering the rate of change for T_c or T_sk. Dynamic responses do occur, especially for T_sk changes (20); however, we observed a similar rate of change for T_c and T_sk during the skin- and the core-treatment phases of the study protocol, so dynamic input was unlikely to have been a confounding variable. In addition, once the target T_sk was reached, T_sk did not change significantly for the remainder of the study. It is possible that vasomotor changes would differ in other areas of the body, but we chose to measure these changes in the fingertip. Fingertip blood flow changes manyfold because of the numerous arteriovenous shunts, and perhaps other skin sites would show a different T_c/T_sk contribution ratio. In our study, however, local temperature changes under the mattresses would have artifactually influenced vasomotor measurements over most other body sites.

In conclusion, cutaneous temperature contributes more toward subjective thermal comfort than to autonomic thermoregulatory responses (vasoconstriction, metabolic heat production, and plasma catecholamine concentrations). The T_c/T_sk contribution ratio is about 1:1 for thermal comfort and from 2:1 to 4:1 for autonomic and metabolic responses. The relatively high cutaneous contribution for thermal comfort may serve to more efficiently utilize behavior as the first-line defense to maintain body temperature in humans, thus avoiding the need for more physiologically demanding adrenergic and metabolic responses.