INDUCTION OF HEAT-SHOCK PROTEIN-72 PROTECTS AGAINST ISCHEMIA-REPERFUSION IN RAT SMALL-INTESTINE

Background & Aims: Induction of heat-shock protein 72 is associated wi th enhanced tolerance to subsequent nonthermal stresses. This study ev aluated whether induction of heat-shock protein 72 protects against in testinal ischemia/reperfusion injury. Methods: Groups of nonheated and heated vats underwent sham operation, 30 minutes of ischemia by occlu sion of the superior mesenteric artery, or ischemia followed by 60 min utes of reperfusion. Whole-body hyperthermia to a core temperature of 41.5-42 degrees C for 15-20 minutes was followed by passive cooling 2- 3 hours before the experiment. Samples of small intestine were obtaine d for determination of heat-shock protein 72 production and ex vivo ge neration of prostaglandin E(2) and leukotriene B-4 and for histologica l assessment of mucosal injury and number of neutrophils. Results: Hyp erthermia significantly increased heat-shock protein 72 production and significantly reduced ischemia/reperfusion-induced mucosal injury, ne utrophilic infiltration, and leukotriene B-4 production. Levels of leu kotriene B-4 and numbers of neutrophils were well correlated in nonhea ted (r = 0.72) but not in heated groups (r = -0.16). The elevation of prostaglandin E(2) levels in response to ischemia and reperfusion was unaltered by hyperthermia. Conclusions: The mechanism of heat stress-i nduced protection against intestinal ischemia/reperfusion injury invol ves inhibition of leukotriene B-4 production and subsequent prevention of neutrophil activation and chemotaxis.