Induction of heat-shock protein 72 protects against ischemia/reperfusion in rat small intestine.
OBJECTIVE
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 degrees 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 E2 and leukotriene B4 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 B4 production. Levels of leukotriene B4 and numbers of neutrophils were well correlated in nonheated (r = 0.72) but not in heated groups (r = -0.16). The elevation of prostaglandin E2 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 B4 production and subsequent prevention of neutrophil activation and chemotaxis.
Stojadinovic
A
A
Department of Surgery, Uniformed Services University of Health Sciences, Bethesda, Maryland, USA.
Kiang
J
J
Smallridge
R
R
Galloway
R
R
Shea-Donohue
T
T
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D005334:Fever; D050884:HSP72 Heat-Shock Proteins; D006339:Heart Rate / Q000502:physiology; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D007421:Intestine, Small / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D007975:Leukotriene B4 / Q000096:biosynthesis; D008297:Male; D009504:Neutrophils / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*
D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D007975:Leukotriene B4