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(American Journal of Pathology. 2002;161:373-379.)
© 2002 American Society for Investigative Pathology

Short Communications

Prophylactic Use of Epidermal Growth Factor Reduces Ischemia/Reperfusion Intestinal Damage

Jorge Berlanga^*, Pedro Prats^*, Diadelis Remirez, Ricardo Gonzalez, Pedro Lopez-Saura^*, Jorge Aguiar^*, Miriam Ojeda^*, Joseph J. Boyle, Anthony J. Fitzgerald and Raymond J. Playford

From the Center for Genetic Engineering and Biotechnology,^*Havana, Cuba; the National Center for Scientific Research,Havana, Cuba; the Department of Histopathology,Hammersmith Hospital, London, England; and the Gastroenterology Section,Imperial College School of Medicine, Hammersmith Campus, London, England

Ischemia/reperfusion of mesenteric vessels is a useful model for acute vascular insufficiency and the early stages of multiorgan failure, conditions associated with high morbidity and mortality. Epidermal growth factor (EGF) is a potent mitogen that shows potential for use in intestinal injury. We therefore examined its influence on this model. Male Sprague-Dawley rats received human recombinant EGF (2 mg/kg i.p., n = 14) or saline (n = 16); 25 minutes before arterial clamping of the superior mesenteric artery (ischemic period) for 60 minutes followed by a final 60-minute reperfusion period. Additional rats were not operated on (controls, n = 7) or had sham operation (laparotomy only, n = 10). Ischemia/reperfusion caused macroscopic damage affecting 56%, 51 to 67% (median, interquartile range), of small intestinal length and intraluminal bleeding. Malondialdehyde levels (free radical marker) increased eightfold compared to nonoperated animals (2400, 2200 to 2700 µmol/mg protein versus 290, 250 to 350 µmol/mg protein, P < 0.01) and myeloperoxidase levels (marker for inflammatory infiltrate) increased 15-fold (3150, 2670 to 4180 U/g tissue versus 240, 190 to 250 U/g tissue, P < 0.01). Pretreatment with EGF reduced macroscopic injury to 11%, 0 to 15%; prevented intraluminal bleeding; and reduced malondialdehyde and myeloperoxidase levels by 60% and 90% (all P < 0.01 versus non-EGF-treated). Mesenteric ischemia/reperfusion also damaged the lungs and kidneys and increased serum tumor necrosis factor- levels (circulating cytokine activity marker). EGF pretreatment also reduced these changes. These studies provide preliminary evidence that EGF is a novel therapy for the early treatment or prevention of intestinal damage and multiorgan failure resulting from mesenteric hypoperfusion.

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