Production of systemic hyperthermia in the rat

The design of clinical trials employing whole-body hyperthermia in cancer therapy has been hampered due to lack of a suitable animal model. We describe a technique for reproducibly and efficiently inducing whole-body hyperthermia in Sprague-Dawley rats, using halothane and oxygen anesthesia and immersion in a hot water bath. Core body temperatures of between 41.5 and 43 degrees C were induced and maintained for periods of up to 200 min and survival curves were determined. The time of exposure at a given temperature that resulted in death in 50% of the animals within 24 hr after heating (LD50/24 hr) was calculated by linear logistic regression analysis. LD50 24 hr values of 115, 61, 57, 25 and 16 min were obtained for temperatures of 41.75, 42.0, 42.25, 42.5 and 42.75 degrees C respectively. This heating technique is compared to several more toxic methods for inducing whole-body hyperthermia with respect to possible pharmacological and physiological differences.