Novel approaches to the pathophysiology of heatstroke: the energy depletion model

De-emphasis of the role of anhydrosis as the primary cause of heatstroke has resulted in increased usage and acceptance of animal models for heatstroke research. When the total amount of work achieved by the running rat prior to exhaustion was plotted against the rate of heat storage, a heretofore unrecognized relationship emerged. These new data suggest that physical exhaustion and heat exhaustion represent opposite ends of a continuum related to the rate of heat storage. Changes in thermoregulatory and/or physical performance can be estimated by a two-dimensional shift in the work-output/thermal storage ratio. Potassium depletion reduces thermoregulatory/physical performance; a combination of atropine plus diazepam appears to improve it. The role of the cholinergic nervous system in eliciting alterations in thermoregulatory and physical ability is reviewed; endurance training, shivering, acclimatization, set-point theory, the anticholinergic syndrome, lithium intoxication, and choline deficiency are discussed.