Nitroglycerin attenuates the bowel damage of necrotizing enterocolitis in a rabbit model.
Endogenous enteric nitric oxide has multiple functions. Enteric nitric oxide may be diminished in the premature infant and may therefore predispose the immature intestine to injury. The aim of this study was to determine if the infusion of a nitric oxide donor (nitroglycerin) would attenuate intestinal damage in a rabbit model of necrotizing enterocolitis. Transmural injection of rabbit intestinal loops with an acidified solution of casein and calcium gluconate simulates certain aspects of necrotizing enterocolitis. After injection of acidified casein solution into rabbit intestinal loops, twelve rabbits were randomly divided into two groups: six received maintenance fluids only and six received maintenance fluids and a nitroglycerin infusion adjusted to maintain mean arterial pressure 10 mm Hg below baseline (range, 2 to 12 micrograms/kg/min). After 3 hours, the rabbits were killed, and the intestinal tissue graded histologically. Intestinal damage in the nitroglycerin-treated rabbits was significantly less than that of untreated controls (mean histological grade of 0.39 v 1.48, P < .001). In this rabbit model of necrotizing enterocolitis, infusion of the nitric oxide donor nitroglycerin significantly attenuates intestinal damage. We speculate that enteric nitric oxide deficiency, as may exist in the preterm infant, predisposes the intestine to necrotizing enterocolitis.
Graf
J L
JL
Department of Surgery, University of California, San Francisco 94143-0570, USA.
VanderWall
K J
KJ
Adzick
N S
NS
Harrison
M R
MR
D000818:Animals; D002125:Calcium Gluconate; D002364:Caseins; D004195:Disease Models, Animal; D004761:Enterocolitis, Pseudomembranous / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D007422:Intestines / Q000473:pathology; D008297:Male; D005996:Nitroglycerin / Q000627:therapeutic use*; D011817:Rabbits
D002364:Caseins; D005996:Nitroglycerin; D002125:Calcium Gluconate