Prophylactic use of epidermal growth factor reduces ischemia/reperfusion intestinal damage.
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 micro mol/mg protein versus 290, 250 to 350 micro mol/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 approximately 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-alpha 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.
Berlanga
Jorge
J
Center for Genetic Engineering and Biotechnology, Havana, Cuba.
Prats
Pedro
P
Remirez
Diadelis
D
Gonzalez
Ricardo
R
Lopez-Saura
Pedro
P
Aguiar
Jorge
J
Ojeda
Miriam
M
Boyle
Joseph J
JJ
Fitzgerald
Anthony J
AJ
Playford
Raymond J
RJ
D000818:Animals; D004815:Epidermal Growth Factor / Q000008:administration & dosage*; D006801:Humans; D007274:Injections, Intraperitoneal; D007422:Intestines / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D008297:Male; D008638:Mesenteric Arteries / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*
D011994:Recombinant Proteins; D004815:Epidermal Growth Factor