A role for gastrointestinal endotoxins in enhancement of heat tolerance by physical fitness

Sakurada, Sotaro, and J. Robert S. Hales. A role forgastrointestinal endotoxins in enhancement of heat tolerance by physical fitness. J. Appl. Physiol.84(1): 207-214, 1998.To further elucidate mechanisms underlyingthe higher heat tolerance of physically fit compared with sedentarypeople, we have investigated the possibility that endotoxins (ofgastrointestinal origin) act, as in the normal development of fever, toraise body temperature and therefore reduce heat tolerance. In aninitial series of experiments, five physically fit and four sedentarysheep were exposed twice at rest to an environment of 42/35°C(dry/wet bulb temperature). When animals were given normal saline iv,rectal temperature (T_re) rose at a significantly higherrate in sedentary than in fit animals; this confirms that heattolerance is improved by physical fitness. Treatment withiv indomethacin did not affect the rate of rise of T_re infit animals. In sedentary animals, however, T_re was loweredto approximate that of fit animals. Because indomethacin blocksprostaglandin pathways involved in endotoxin-induced fever, theindomethacin-induced improvement of heat tolerance of sedentary but notfit animals supports the contention that endotoxins play a role indetermining that difference in heat tolerance. In a second series ofexperiments, quantitative cardiovascular measurements were made byusing radioactive microspheres. Under normothermic conditions, bloodflows in the brain, ileum, and diaphragm were higher in fit than insedentary animals. During hyperthermia up to T_re of42°C (in a 42/39°C environment), fit compared with sedentary animals exhibited 1) a greaterincrease in cardiac output, 2) anincrease in blood flow through arteriovenous anastomoses to higher andbetter maintained levels, 3) lessreduction in blood flow to the ileum, and4) greater increase in blood flowsto the myocardium, turbinates, nasal mucosa, and respiratorymuscles. Endotoxins are likely to come from the gut lumen,because reduction of gut blood flow forms part of the normal responseto heat stress. We suggest that improvement of heat tolerance byphysical fitness is caused by a greater cardiovascular capacity thatpermits not only greater perfusion of heat-loss tissues but themaintenance of a better gastrointestinal tract blood supply, therebybetter maintaining the normal barrier to movement of endotoxins from gut lumen to plasma. Sedentary people, with their lower cardiovascular capacity, redistribute more blood flow away from the gut during environmentally induced hyperthermia, thus allowing endotoxin-induced fever to aggravate hyperthermia.