Eur J Appl Physiol (1986) 55:410--412 European Journal of Applied Physiology and Occupational Physiology 9 Springer-Verlag 1986 Increase in rat intestinal permeability to endotoxin during hyperthermia Y. Shapiro 1, M. Alkan 1, Y. Epstein 2, F. Newman 2, and A. Magazanik 2 1 Ben-Gurion University Faculty of Health Sciences and Soroka Medical Center, Beer-Sheva, and 2 Heller Institute of Medical Research, Chaim Sheba Medical Center, 52621 Tel-Hashomer, Israel Summary. Victims of heat stroke exhibit several clinical features which are also encountered in en- dotoxaemia. In order to investigate these similari- ties hyperthermic rats were used to explore the possibility that high body temperature results in increased permeability of intestinal wall to endo- toxin. 1251 endotoxin was introduced into intesti- nal segments taken from non-heat exposed rats. The segments were then incubated at 37~ or 45 ~C. Intestinal segments from heat stressed rats were similarly prepared and incubated at 37~ Leakage of endotoxin from segments taken from heat stressed rats was three times greater than from those from non-heat stressed rats, as were the segments from non-heat stressed rats which were incubated at 45 ~C. These results indicate that the intestinal membrane is damaged by heat and that an increase in outward leakage of micro- bial endotoxins from the gut then occurs. This might contribute to the pathophysiological pic- ture of heatstroke. Key words: Endotoxin -- Hyperthermia Introduction Victims of heatstroke exhibit several clinical and pathological features which are also encounterr in endotoxaemia, these being massive increase in capillary permeability, oedema, gastrointestinal bleeding, general circulatory failure, blood clot- ting disturbances, altered acid base balance, kid- ney failure, shock and a high death rate (Rosen- thal et al. 1971 ; Shibolet et al. 1976; Ollodart et al. 1967; Dietzman et al. 1969; Cuevas et al. 1972; Offprint requests to: Y. Epstein at the above address Wolff 1973; Wardle 1974; Magazanik et al. 1980). Bacterial endotoxin is present in very large amounts in the intestine, but normally only min- ute quantities penetrate into the circulation (Car- idis et al. 1972; Hamer-Hodges et al. 1974; Prytz et al. 1976). It has been suggested that endotoxins are involved in the development of the patholog- ical picture of heatstroke (Shibolet et al. 1976; As- sia et al. 1985). The appearance of measurable amounts of enteric endotoxin in the peripheral blood could be the cause or the result of increased permeabil- ity of the intestinal epithelium (Walker et al. 1978) with or without a decrease in hepatic detoxifica- tion (Aballi et al. 1978). Increased concentration of endotoxin in the intestinal lymphatics could bypass the liver and directly elevate the levels in the systemic circulation. Hepatic failure directly causes systemic endotoxaemia (Wilkinson et al. 1974) which results in further damage to this or- gan (Nolan 1975). This has been shown to contri- bute to mortality from large burns (Cuevas et al. 1974). The origin of endotoxin in all these cases seems to be from the intestinal flora (Gans et al. 1974). The present study investigates the possibility that high temperature results in increased permea- bility of the intestinal wall to endotoxin, enabling its passage into the circulation. This may contri- bute further to the laypothesis that endotoxins play a role in the pathological picture of heat- stroke. Methods Endotoxin (DIFCO E. coli 055:85) was separated from low molecular weight contaminants by a Sephadex G-200 column.