Induction of heat-shock protein 72 protects against ischemia/reperfusion in rat small intestine

Abstract Background & Aims: Induction of heat-shock protein 72 is associated with enhanced tolerance to subsequent nonthermal stresses. This study evaluated whether induction of heat-shock protein 72 protects against intestinal ischemia/reperfusion injury. Methods: Groups of nonheated and heated rats underwent sham operation, 30 minutes of ischemia by occlusion of the superior mesenteric artery, or ischemia followed by 60 minutes of reperfusion. Whole-body hyperthermia to a core temperature of 41.5–42°C for 15–20 minutes was followed by passive cooling 2–3 hours before the experiment. Samples of small intestine were obtained for determination of heat-shock protein 72 production and ex vivo generation of prostaglandin E 2 and leukotriene B 4 and for histological assessment of mucosal injury and number of neutrophils. Results: Hyperthermia significantly increased heat-shock protein 72 production and significantly reduced ischemia/reperfusion-induced mucosal injury, neutrophilic infiltration, and leukotriene B 4 production. Levels of leukotriene B 4 and numbers of neutrophils were well correlated in nonheated ( 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-induced protection against intestinal ischemia/reperfusion injury involves inhibition of leukotriene B 4 production and subsequent prevention of neutrophil activation and chemotaxis.