INTRODUCTION

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PREVIOUSLY REPORTED EXPERIMENTAL observations raise the possibility that prolonged or repeated cold exposure and/or physical exertion might result in "thermoregulatory fatigue" characterized by impaired shivering (2, 14), impaired vasoconstrictor responses (1), or both, which in turn reduce the ability to defend body temperature (1). Two possible mechanisms may explain how exhaustive exercise might increase susceptibility to hypothermia. First, exertional fatigue induced by exhaustive exercise could simply cause a person to be unable to sustain a sufficiently high exercise intensity (e.g., subjects walk at a slower pace) for metabolic heat production () to exceed the rate of heat loss; therefore, body core temperature falls (9). Second, thermoregulatory effector responses that act to defend thermal balance in the cold (i.e., shivering or peripheral vasoconstriction) could become blunted, directly as a result of prolonged activation or indirectly because of exhaustive exercise. The latter mechanism is consistent with the experimental observation of Thompson and Hayward (9) that one of their subjects was able to walk continuously at an unchanged pace (exercise intensity = 450 W) throughout a prolonged cold exposure, but after several hours, his decreased, and then core temperature fell rapidly. The authors' interpretation of that observation was that, initially, measurements reflected contributions from exercise thermogenesis and shivering thermogenesis but, with fatigue, the contribution due to shivering declined. Our laboratory recently demonstrated that individuals experiencing severe exertional fatigue (14) or serial cold water immersions (2) also exhibit a blunted shivering response to cold. Although these studies suggest that shivering may become fatigued, their experimental designs may have introduced confounding factors weakening that interpretation. For example, in the subject studied by Thompson and Hayward, hypoglycemia may have impaired shivering. In subjects studied by Young et al. (14), exertional fatigue was coupled with sleep loss and chronic negative energy balance. Our own experiments (1) and those of others (10, 12) demonstrated no impairment from a single, acute bout of fatiguing exercise on shivering responses during subsequent cold exposure.

Recently, new evidence suggesting that exhaustive exercise might impair vasoconstrictor responses during cold exposure has been reported. Subjects' maintained higher mean skin temperatures (_sk) (10) and greater peripheral heat loss (1) when cold exposures followed 1-5 h of fatiguing exercise than when cold exposures were completed when subjects were rested. However, an alternate explanation for those experimental findings (1, 10) is that the blunting of vasoconstrictor responses to cold resulted from peripheral hyperemia developed during the preceding acute exercise bout, rather than impaired vasoconstrictor responses.

The extent to which exhaustive exercise can affect thermoregulatory responses during cold exposure, independently of sleep deprivation, caloric restriction, and hypoglycemia, remains unknown. The purpose of this study was to determine whether multiple days of strenuous, fatiguing exercise would impair thermoregulation during cold-wet (CW) exposures and increase susceptibility to hypothermia. It was hypothesized that strenuous exercise performed for 7 consecutive days would blunt shivering thermogenesis and peripheral vasoconstriction, allowing a greater fall in core temperature during cold exposure. CW exposures were employed to provide significant heat loss that could be extended over many hours. In addition, to standardize effects of exercise-induced hyperemia during cold exposure among all trials, exercise at a fixed intensity was performed during each CW exposure. This type of exercise-CW exposure provides a model applicable to many military and recreational emergency scenarios.

	METHODS

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Subjects

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Preliminary testing. Body composition was measured using dual-energy X-ray absorbitometry (model DPX-L, Lunar, Madison, WI). An incremental treadmill test was used for determination of O_2 peak. Briefly, subjects ran at 9.7-11.3 km/h at a 0% grade for 1.5 min. Thereafter, the grade increased 2% every 1.5 min until the subject became exhausted. The one repetition maximum (1 RM) of the upright row, chest press, latissimus dorsi pull down, and biceps curl was determined for members of the Ex group but not the control group. Subjects completed a series of no more than six single repetitions as resistance was increased incrementally until the subject could no longer lift the weight correctly. Approximately 1 min elapsed between successive 1-RM attempts.

Experimental design. The subjects' body composition, O_2 peak, and muscle strength were assessed before the beginning of the experiment. The subjects then completed three experimental CW walks from ~1330 to 2000 when they were well rested before beginning the heavy exercise regimen (day 0) and after 3 and 7 consecutive days of exhaustive exercise (Ex group) or at the same between-trial intervals for the control group. The purpose of including the control group was to assess the possibility that three repeated exposures to cold completed over a 1-wk period would induce habituation or acclimatization to cold, separate from effects of the exhaustive exercise, although the small sample number may limit statistical inferences. The control group refrained from any exercise for 24 h before each CW exposure. On days 3 and 7, ~2.5 h (140-170 min) elapsed between the end of the last daily exercise session and the subsequent CW exposure. The CW exposure was modified from an experimental protocol described by Weller et al. (13). Briefly, the CW exposure consisted of 360 min of intermittent treadmill walking (6 cycles of 10 min of standing rest in the rain, 45 min of walking, 5 min of transition between rest and walking) in an environmental chamber with air temperature set at 5°C. During the rain, the subjects stood still for 10 min (except for the initial cycle of rain, during which they sat) and were wetted at a rate of 5.41 cm/h under a sprinkler designed to simulate rainfall. After each rest-rain period, subjects walked at 1.34 m/s (3 miles/h) at 0% grade on a motor-driven treadmill. Wind velocity was 1.1 m/s (2.5 mph) during the 10-min rain and 5.4 m/s (12 mph) during the period of walking. The CW exposure for each subject was terminated if the rectal temperature (T_re) was <35°C or if the subject asked to stop.

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Measurements and calculations. T_re was measured every minute using a thermistor inserted 10 cm past the anal sphincter. Skin temperature (T_sk) was measured using thermistor disk sensors (Concept Engineering, Old Saybrook, CT) attached on the skin surface at five sites (ventral aspect of forearm, tricep, subscapula, anterior thigh, calf). _sk was calculated as follows: _sk = 0.28T_subscapular + 0.14T_forearm + 0.08T_triceps + 0.22T_calf + 0.28T_thigh. HR was measured near the end of each walking portion of the CW exposure from three chest electrodes (CM-5 configuration) and radiotelemetered to an oscilloscope-cardiotachometer (Hewlett-Packard). O₂, CO₂ output, and minute ventilation were measured by open-circuit spirometry before the CW exposure (sitting) and during minutes 25-27 of walking during each exercise portion of the rest-walking cycle. Additionally, in four subjects from the Ex group and the three control subjects, expired air was collected immediately after the rain portion of each cycle to evaluate shivering thermogenesis during rest. Percent O₂ (model S-3A, Applied Electrochemistry), CO₂ (model LB-2, Beckman), and volume (Tissot spirometer, Collins) were measured from a 1.5-min collection of the subjects' expired air into a Douglas bag. (W/m²) was estimated from the O₂ and respiratory exchange ratio (RER) using the following equation (6):  = [0.23(RER) + 0.77] · (5.873)(O₂) · (60/A_D), where A_D (4) is body surface area (m²). Whole body insulation (I) was calculated using the following equation: I = (T_re  sk)/. Self-reported dietary and sleep records were kept each day beginning on the day before the first CW exposure and continuing through day 7.

Statistical analyses. Data were analyzed using a two-factor (time × experimental trial) repeated-measures ANOVA. When significant F ratios were calculated, paired comparisons were made post hoc using Fisher's least significant difference test. Because exposure duration varied for each subject among the three trials, statistical analysis was performed on complete data sets for all three trials. For the Ex group, data from 10 subjects were analyzed from 0 to 180 min and data from four subjects were analyzed for 360 min. For the control group, data from the three subjects were analyzed for 240 min. There were missing data points at various points because of difficulty in drawing blood samples from subjects during cold exposure. Therefore, catecholamine data were analyzed with t-tests between days 0 and 3 and between days 0 and 7. Unless otherwise specified, the level of significance for differences reported is P < 0.05. Values are means ± SE.

	RESULTS

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Exercise Duration, Cold Tolerance, Food, and Sleep Diaries

Control Group Responses

Temperature Regulation Responses (Ex Group)

T_re. T_re was significantly higher during the first 2 h (n = 10, F = 3.67, P < 0.001) and significantly lower in the 6th h of cold exposure (n = 4, F = 2.02, P < 0.001) on day 3 than on day 0 (Fig. 1). T_re was also significantly higher in the 2nd and 3rd h (n = 10) of cold exposure on day 7 than on day 0, with no difference between these trials for the last 3 h (n = 4) of exposure. The change in T_re, relative to the initial T_re at time 0, was significantly greater (F = 3.68, P < 0.001) during the 6th h of cold exposure on day 3 than on day 0.

View larger version (15K): [in this window] [in a new window]   Fig. 1.   Rectal temperature vs. time during cold exposure before (D0) and after 3 days (D3) and 7 days (D7) of physical exertion. Data from 0 to 180 min are from 10 subjects, and data from 190 to 360 min are from 4 subjects. *D3 significantly (P < 0.05) different from D0; #D3 significantly (P < 0.05) different from D0 and D7. Fisher's least significant difference was used for post hoc analysis.

T_sk. _sk values were significantly higher (F = 3.17, P < 0.001) on days 7 and 3 than on day 0 from the 1st to the 6th h of cold exposure (Fig. 2). The change in _sk (a measure of the magnitude of vasoconstrictor response) was significantly less (F = 3.17, P < 0.001) in the 2nd and 3rd h (n = 10) on day 7 than on days 0 and 3. The _sk for the 3rd-6th h was significantly less on days 7 and 3 than on day 0. Forearm T_sk during the first 3 h of cold exposure demonstrated a significantly smaller fall (F = 1.63, P < 0.05) on days 3 and 7 than on day 0, and the fall in calf T_sk during the same time period was also significantly less (F = 2.35, P < 0.001) on day 7 than on days 0 and 3.

View larger version (15K): [in this window] [in a new window]   Fig. 2.   Mean skin temperature vs. time during cold exposure before and after 3 and 7 days of physical exertion. Data from 0 to 180 min are from 10 subjects, and data from 190 to 360 min are from 4 subjects. D3 and D7 significantly (P < 0.05) different from D0; #D3 significantly (P < 0.05) different from D0 and D7; $D7 significantly (P < 0.05) different from D0. Fisher's least significant difference was used for post hoc analysis.

, insulation, HR, and thermal sensation. increased from rest during all three cold exposures (Fig. 3), with no differences among trial days. A higher was observed during the rest-rain periods through the third rain period on day 3 than on days 0 and 7 (Table 3). Whole body insulation was less (F = 11.62, P < 0.01) on days 3 and 7 than on day 0 during the last 3 h of cold exposure (Fig. 4). Forearm insulation was lower (F = 8.33, P < 0.01) on days 3 and 7 than on day 0, and there were no differences among days for calf insulation. HR was significantly higher (main effect, F = 4.52) on day 3 than on day 0 during the first 3 h of cold exposure. HR was similar before and during the first 3 h of exercise-cold stress (Table 4). Thermal sensation was similar among trial days during cold exposure.

View larger version (14K): [in this window] [in a new window]   Fig. 3.   Metabolic heat production vs. time during cold exposure before and after 3 and 7 days of physical exertion. Data from 0 to 180 min are from 10 subjects, and data from 190 to 360 min are from 4 subjects.

View larger version (24K): [in this window] [in a new window]   Fig. 4.   Insulation vs. time during cold exposure before and after 3 and 7 days of physical exertion. Data from 0 to 180 min are from 10 subjects, and data from 190 to 360 min are from 4 subjects. D3 and D7 significantly (P < 0.05) different from D0. Fisher's least significant difference was used for post hoc analysis.

Blood Responses

View larger version (17K): [in this window] [in a new window]   Fig. 5.   Plasma norepinephrine (A) and epinephrine (B) concentrations at 0700 (baseline) and after cold exposure (post-CW) before and after 3 and 7 days of exhaustive exercise. Number of subjects for each time point for norepinephrine and epinephrine is indicated in parentheses. D3 and D7 significantly different (P < 0.05) from D0. t-Tests were used to determine statistical differences between days.

	DISCUSSION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

This study investigated whether a regimen of multiple days of strenuous physical exertion might induce "thermoregulatory fatigue" (1), characterized by blunted shivering and vasoconstrictor responses during cold exposure relative to cold exposure responses measured before the fatiguing exercise regimen was completed. Exhaustive exercise and fatigue have been suggested to impair shivering responses during cold exposure (8, 9, 14). However, in those earlier studies, the effect of exercise-induced fatigue on thermoregulatory responses to cold is difficult to discern independent of other potential confounding factors that could affect shivering, such as sleep deprivation, negative energy balance, and hypoglycemia. This is the first study to examine the cumulative effects of consecutive days of severe physical exertion on thermoregulatory responses to prolonged cold exposure while controlling for such confounders. The development of cold habituation could also be ruled out as a potential confounder in this study, because the design included a control group that completed the repeated cold exposure experiments without participating in the intervening exercise regimen and demonstrated no between-trial differences in thermoregulatory and body temperature responses. The principal finding from these experiments was that multiple days of physical exertion appeared to impair vasoconstrictor responses to cold, but not shivering. This impairment, reflected by higher T_sk than with the "rested" trial, caused T_re to be significantly lower during cold exposure after 3 days of exhaustive exercise.

_sk values were higher during cold exposures completed after multiple days of physical exertion. In an earlier study in which subjects rested quietly during a cold exposure completed shortly (20 min) after they had finished a single, acute bout of lower body exercise, our laboratory observed a similar effect (1). One possible mechanism to account for the warmer T_sk values after exercise than in trials not preceded by exercise was an elevated peripheral blood flow resulting from vasoconstrictor fatigue during the cold exposure, but our laboratory acknowledged that the persistence of a postexercise hyperemia in active muscles during the cold exposure could also increase convective heat transfer from the body's core to the periphery overlying active muscle (1). Our laboratory termed the latter mechanism "heat redistribution" to distinguish it from the former, which we termed thermoregulatory fatigue (1). However, we believe that the higher T_sk values observed in the present investigation during cold exposures completed after 7 days of exhaustive exercise do not represent the heat redistribution mechanism. In the present study, subjects performed standardized exercise of the same intensity during all the cold exposures, so muscle blood flow, and thus heat redistribution, should have been constant among trials. Therefore, we believe that our observations indicate that fatigue induced by exhaustive exercise may indeed blunt the vasoconstrictor response during cold exposure.

The blunting of the vasoconstrictor response to cold subsequent to severe physical exertion may be related to concomitant elevations in basal circulating NE levels that we observed in the day 3 and day 7 trials. Opstad (7) observed higher circulating NE levels in soldiers after multiple days of exhaustive exercise coupled with sleep deprivation, and Young et al. (14) reported similar effects in soldiers who had just completed an 8-wk training course that entailed heavy physical exertion throughout the course coupled with sleep deprivation and negative energy balance. In this study, we observed that basal NE levels were elevated in our subjects after 3 and 7 consecutive days of exercise. Despite the elevation of basal NE concentrations, similar sympathetic activation was elicited during all three cold exposures, as evidenced by the increment in NE concentrations over preexposure levels observed by the end of each of the cold exposures, the magnitude of which did not differ among trials. Stimulation of adrenergic receptors is thought to be the primary mechanism that mediates cold-induced vasoconstriction (5). Because the increment in NE, relative to preexposure levels, was similar during all three cold exposure trials, a blunted sympathetic nervous stimulus does not appear to account for the less pronounced vasoconstrictor response. However, a diminished sensitivity of the adrenergic receptors remains as a viable mechanism to explain the blunting of cold-induced vasoconstriction. Chronically elevated NE levels have been shown to decrease adrenergic receptor sensitivity in animal models (11), and similar effects have been suggested to develop in humans in whom circulating NE levels remain chronically elevated (7). Future studies should directly evaluate the role of elevated sympathetic activity on cold-induced vasoconstriction.

Shivering thermogenesis was unimpaired by multiple days of exhaustive exercise. Previously, our group (1) and others (10, 12) reported that a single acute (1-5 h) exercise bout had no fatiguing effect on shivering during subsequent cold exposures. Thus shivering thermogenesis may not be easily fatigable (1). Shivering, by and of itself, is a relatively low-intensity activity (15). It may be that exhaustive exercise must be coupled with other factors such as sleep deprivation, caloric deprivation, or hypoglycemia before this thermoregulatory effector response is blunted.

Many subjects were unable to continue walking for 6 h in the cold-wet conditions because of muscle cramping (n = 4), leg and knee pain (n = 2), and general muscle stiffness (n = 1). If these volunteers were subjected to wet-cold conditions in a scenario where they could not escape the cold after discontinuing exercise, shivering alone would be insufficient to offset heat loss, and core temperature would fall. Weller et al. (13) and Thompson and Hayward (9) demonstrate this elegantly in their studies when exercise intensity decreases during prolonged cold-wet exposure. Thus physical exertion affects the ability to maintain normal body temperatures during cold exposure via direct (i.e., impairing thermoregulatory response) and indirect (impairing capacity to increase metabolic heat production) mechanisms.

One potential criticism of the present study is that the fatigue induced over 1 wk was not qualitatively or quantifiably measured. Historically, studies (1, 8-10, 14) that have examined the role of physical fatigue on thermoregulation in the cold have used an experimental approach similar to ours and have not utilized a measurable fatigue index. The present study addressed the effects of a nonnutritionally related, non-blood-flow-related, non-sleep-status-related, and non-hydration-related aftereffect of chronic severe physical exertion. We believe that aftereffect can be properly termed fatigue, and thus fatigue related to exhaustive exercise was the primary factor responsible for the between-trials treatment effect observed and discussed here.

In conclusion, this study examined the effects of multiple days of exhaustive exercise on temperature regulation during prolonged cold exposure. Our findings demonstrate that, after several days of severe physical exertion, the vasoconstrictor response to cold exposure is blunted, perhaps because of a fatigue-related mechanism. In contrast, shivering thermogenesis appears less sensitive to the effects of previous physical exertion. Increases in peripheral heat loss during prolonged cold-wet exposure associated with impaired vasoconstrictor responses to cold would eventually exacerbate the fall in core temperature, if metabolic heat production is unchanged, thereby increasing susceptibility to hypothermia. These findings have implications for individuals, such as hikers, military personnel, and outdoor workers, who are exposed to cold-wet environments and have been engaged in heavy, fatiguing exercise for many days.