The Effects of Cortisol, Corticosterone, Insulin and Glucose Pre- and Post-Treatment on Heatstroke in Rats and the Kinetics of Uptake and Cellular Response.

In studies of heat stress, a series of in vivo and in vitro experiments were designed to determine if mixtures of either cortisol or corticosterone plus insulin and glucose have beneficial effects on hyperthermic rats. Hyperthermia was induced in male rats 450 to 550 grams by exposure to severe heat loads 42 C to 42.6 C. The rats were then allowed to cool to or below 40.4 C. Blood samples were taken at this point or after 24 hours of survival depending upon the experimental protocol. Endogenous corticosterone, LDH, SGOT and potassium levels increased immediately. In the 24-hour viability studies, rats were injected after heat stress with post-treatment regimens of corticosterone, insulin and glucose in solution. Our results show that the number of control rats 15 which died after heat exposure was three times greater than the number which had been post-treated 5 after heat exposure. Studies using isolated hepatocytes showed that a mixture of corticosterone, insulin and glucose caused minor reductions in the SGOT and LDH levels due to hyperthermia. Further investigations were conducted using I-125 labeled corticosterone to study the biodistribution patterns of the radiolabeled compound in the heat-stressed and unheated control animal model. The rat livers were further analyzed for I-125 labeled corticosterone content in order to identify liver subcellular localization patterns. Our results show that i.v. post-treatment of the rats with the indicated drug mixture is valuable in treating heatstroke.