16,16-Dimethyl prostaglandin E2 reverses focal mucosal ischemia associated with stress ulcers.
Focal ischemia is postulated to contribute to gastric mucosal stress ulceration. This study evaluated directly whether or not mucosal ulceration during hemorrhagic shock is preceded by focal gastric mucosal blood flow changes, and whether or not topical Dm-PGE2 (16,16-dimethyl prostaglandin E2) 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 mM HCl. Gastric mucosal blood flow was documented by radiolabeled microspheres during normotension, initial hemorrhagic shock (50 mm Hg), and hemorrhagic shock + 50 micrograms topical Dm-PGE2. 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 less than 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 less than 0.05 vs surrounding tissue). Addition of Dm-PGE2 increased blood flow to shed tissue from 29 +/- 8% to 48 +/- 10% of blood flow to intact tissue (P less than 0.05).


CONCLUSIONS
(1) gastric mucosal ulceration is preceded by focal decreases in gastric mucosal blood flow, and (2) topical Dm-PGE2 reverses focal mucosal ischemia during hemorrhagic shock. Dm-PGE2's ability to reverse focal ischemia suggests a mechanism for prostaglandin-mediated cytoprotection.
D015064:16,16-Dimethylprostaglandin E2 / Q000627:therapeutic use*; D000287:Administration, Topical; D000818:Animals; D005753:Gastric Mucosa / Q000098:blood supply*; D007511:Ischemia / Q000150:complications / Q000188:drug therapy*; D011459:Prostaglandins E, Synthetic / Q000627:therapeutic use*; D012039:Regional Blood Flow; D012771:Shock, Hemorrhagic / Q000150:complications; D013276:Stomach Ulcer / Q000150:complications* / Q000209:etiology; D013312:Stress, Physiological / Q000150:complications*; D013552:Swine; D013556:Swine, Miniature; D013997:Time Factors
D011459:Prostaglandins E, Synthetic; D015064:16,16-Dimethylprostaglandin E2