Epidermal growth factor reduces ischemia-reperfusion injury in rat small intestine.
OBJECTIVE
To measure the effect of pre-ischemic administration of intraluminal epidermal growth factor on the changes in intestinal permeability induced by 30 mins of superior mesenteric artery occlusion, followed by 2 hrs of reperfusion.


METHODS
Prospective, randomized, placebo-controlled experimental study.


METHODS
University basic science research laboratory.


METHODS
Healthy, young, adult, male Sprague-Dawley rats.


METHODS
A 10-cm segment of small intestine was isolated and studied in situ in rats that were anesthetized with fentanyl and mechanically ventilated. Intestinal ischemia-reperfusion injury was induced by temporary occlusion of the superior mesenteric artery for 30 mins, followed by 2 hrs of reperfusion. Three groups were studied: time controls with a sham operation, saline-treated ischemia-reperfusion, and epidermal growth factor-treated ischemia-reperfusion. Epidermal growth factor, 100 ng/min, was infused intraluminally, beginning 30 mins before and continued until 40 mins after ischemia.


RESULTS
Intestinal permeability was measured for each 10-min time period by using chromium-labeled EDTA. Histopathologic injury was assessed by light microscopy. After superior mesenteric artery occlusion, intestinal permeability increased approximately ten-fold and was sustained for 2 hrs of reperfusion in saline-treated rats. Pretreatment with epidermal growth factor significantly reduced the permeability changes during reperfusion by >60% compared with saline-treated animals (p <.05). Histopathologic sections revealed apparently more extensive loss of epithelial cells and mucosal disruption in saline-treated intestine compared with epidermal growth factor-treated intestine.


CONCLUSIONS
Pre-ischemic administration of intraluminal epidermal growth factor significantly protects against intestinal ischemia-reperfusion injury.
Department of Pediatrics, University of Miami School of Medicine, Miami, FL, USA.
Xavier
X
Villa
John W
JW
Kuluz
Charles L
CL
Schleien
John F
JF
Thompson
D000818:Animals; D004815:Epidermal Growth Factor / Q000494:pharmacology / Q000627:therapeutic use*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007421:Intestine, Small / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy*
D004815:Epidermal Growth Factor