A total of 252 untrained, unacclimatized, and unanesthetized laboratory rats weighing between 485 and 545 g were fasted and either run to exhaustion at 5, 20, 23, or 26 degrees C or were restrained and heated at an ambient temperature of 41.5 degrees C. The incidence of mortality associated with a wide range of work-induced hyperthermias was compared to the lethality of equivalent heat loads in the absence of physical effort. The severity of hyperthermia was calculated in degree-minutes above a base-line core temperature of 40.4 degrees C. The LD25′s of run-exhausted versus restrained-heated rats were 16.8 and 30.1 deg-min, respectively. Survivors had a faster cooling rate than fatalities, but run-exhausted survivors had a slower cooling rate than restrained-heating survivors. Results indicate that 1) both the incidence of mortality and the survival time can be predicted from the severity of core heating, 2) work-related factors contribute to an increased rate of heatstroke death at low thermal loads, and 3) retrospectively, both heat-sensitive and heat-resistant groups were identified.

To assess the lethal effects of work-induced hyperthermia on exercising animals, untrained rats were run to exhaustion at 5 and 20-26 degrees C or restrained at 41.5 degrees C. An exercise-induced core temperature of 40.4 degrees C represented a base line above which mortalities occurred. With increasing core temperature at exhaustion (between 40.4 and 43 degrees C), mortality increased within 24 h. A dose-respones curve with an LD50 equivalent to a core temperature of 41.5 +/- 0.1 degrees C was calculated. Although differences in body weight loss, core temperature at exhaustion, and cooling rate will clearly distinguish between survivors and fatalities, the severity of heat injury as inferred from survival times is best measured by the time versus intensity of hyperthermia in degree-minutes.

A total of 171 untrained, unacclimatized, and unanesthetized rats were used to evaluate the effects of sedentary and work-induced hyperthermia on the incidence of mortality and cellular injury, 24 h postexposure. Cellular injury was defined as serum transaminase activity (SGPT and SGOT) exceeding 1,000 IU/l (heatstroke levels). Both the percent mortality and the percentage of 24-h survivors with transaminase levels above 1,000 IU/l were plotted against maximum core temperatures. Exertion-induced hyperthermia produced a significantly higher incidence of cellular injury and heatstroke death at lower core temperatures than hyperthermia alone. With hyperthermia only, the SGPT and SGOT dose-response curves were identical. When work was combined with hyperthermia, there was a greater incidence of elevated SGOT at lower core temperatures. These curves bore a striking resemblance to curves reflecting heat- and/or work-induced mortality in humans. The results suggest a direct role of physical effort in causing heatstroke injury and mortality.

A total of 171 untrained, unacclimatized, and unanesthetized rats were either exercised to exhaustion at one of four ambient temperatures (5, 20, 26, or 30 degrees C), or were restrained and heated at an ambient temperature of 41.5 degrees C until their core temperatures reached a preselected end point between 41.0 and 43.3 degrees C. The serum levels of creatine phosphokinase (CRK) and two transaminases (SGOT and SGPT) were determined at 30 min, 24, 48, 72, and 96 h posttreatment. Peak enzyme activity for CPK was noted primarily at the 30-min sampling period and at 24 h for the transaminases. The data indicated that under these conditions a) the transaminase SGOT was elevated in the serum as a consequence of the extent and duration of prior hyperthermia, b) the transaminase SGOT was released in moderate amounts after exhaustive exercise but reached its greatest activity levels following hyperthermia, and c) the activity of CPK was increased by the duration of exhaustive exercise and was less sensitive than either transaminase to prior hyperthermia. As a result, each of the three experimental conditions: a) exercise without hyperthermia, b) exercise with hyperthermia, and c) sedentary hyperthermia, produced a unique pattern of serum enzyme activity that would appear useful in diagnosing a variety of heat- and/or work-induced disorders.

To develop a reliable procedure for the acute expansion of plasma volume (PV), 26 male volunteers were randomly assigned to either a thermoneutral (25 degrees C and 40% relative humidity) or hot-dry (37 degrees C and 25% relative humidity) environment; subsequently each subject was seated for at least 1 h and then infused intravenously with either 100 or 200 ml of a 25% albumin solution or 0.9% saline. On the day before each infusion, PV was estimated by dye dilution using indocyanine green. Net percent change in PV (using hematocrit and hemoglobin values) was calculated at 1, 3, 6, 9, 12, and 24 h postinfusion. The PV of subjects residing in the heat after a 100-ml saline infusion increased significantly over 1-h values at 6, 9, and 12 h postinfusion but not at 24 h. The same trend, although not significant, was apparent at room temperature. The data suggest a slow isooncotic circadian pattern of PV expansion and contraction. The infusion of hyperoncotic albumin produced rapid expansion of plasma volume. With the low dose (25 g) at 1 h postinfusion, the expansion was 379 +/- 102 ml in the heat and 301 +/- 160 ml at room temperature. With the high dose (50 g) at 1 h postinfusion, the expansion was 479 +/- 84 ml in the heat and 427 +/- 147 ml at room temperature. The high dose produced an expansion that persisted for at least 9 h in subjects in either environment. The data suggest a mechanism for the retention of fluid during heat acclimatization and a useful procedure for plasma volume expansion in humans.