16,16-Dimethyl prostaglandin E 2 reverses focal mucosal ischemia associated with stress ulcers

Abstract

Focal ischemia is postulated to contribute to gastric mucosal stress ulceration. This study evaluated directly (1) whether or not mucosal ulceration during hemorrhagic shock is preceded by focal gastric mucosal blood flow changes, and (2) whether or not topical Dm-PGE 2 (16,16-dimethyl prostaglandin E 2) affects focal gastric mucosal blood flow during hemorrhagic shock. Twelve anesthetized miniature swine had pyloric ligation and intragastric infusion of 5 ml/kg autogenous bile in 140 m M HCl. Gastric mucosal blood flow was documented by radiolabeled microspheres during (1) normotension, (2) initial hemorrhagic shock (50 mm Hg), and (3) hemorrhagic shock + 50 μg topical Dm-PGE 2. Stable shock was then maintained for 3 hr. During this time ulceration developed, shedding radiolabeled microsphere-bearing mucosa into the lumen. Intact gastric mucosa and luminal contents were collected, weighed, and gamma counted. Blood flow to intact mucosa was calculated by standard techniques. The weight of shed tissue, as well as the blood flow to shed tissue, was calculated from luminal microspheres. Results: gastric mucosal blood flow was decreased 35% with hemorrhagic shock (28.8 ± 4.0 vs 18.7 ± 2.7 ml/100 g/min, P < 0.05). Blood flow to tissue which was subsequently shed averaged 6.4 ± 3.1 ml/100 g/min at the same time period ( P < 0.05 vs surrounding tissue). Addition of Dm-PGE 2 increased blood flow to shed tissue from 29 ± 8% to 48 ± 10% of blood flow to intact tissue ( P < 0.05). Conclusions: (1) gastric mucosal ulceration is preceded by focal decreases in gastric mucosal blood flow, and (2) topical Dm-PGE 2 reverses focal mucosal ischemia during hemorrhagic shock. Dm-PGE 2's ability to reverse focal ischemia suggests a mechanism for prostaglandin-mediated cytoprotection.