rioprostil and Gastrointestinal-Hemorrhage

Rioprostil, a primary alcohol prostaglandin E1 analog, prevents gastric lesion formation induced by a variety of irritants, including aspirin, in rats and dogs. In the present study, rioprostil reduced both gastric lesion formation and fecal blood loss in dogs caused by daily aspirin administration (1,950 mg/day) for 3 consecutive days. A gastric antisecretory dose of 100 micrograms/kg p.o. t.i.d. of rioprostil reduced fecal blood loss by 96% to a level (0.76 +/- 0.10 mg Hb/g stool) similar to basal blood loss in non-aspirin-treated vehicle dogs (0.61 +/- 0.08 mg Hb/g stool) as determined by HemoQuant assay. A nonantisecretory dose of rioprostil (1 microgram/kg p.o. t.i.d.) reduced fecal blood loss by 70% compared to vehicle-treated dogs. Gastric lesion severity scores in dogs treated with 100 or 1 micrograms/kg p.o. t.i.d. of rioprostil were 61 and 52% lower, respectively, than the mean severity score in the vehicle-treated group. There was a highly significant (p less than 0.001) correlation between gastric lesion score and fecal blood loss independent of the treatment each dog received. The efficacy of a nonantisecretory dose suggests that the gastric lesion effect of rioprostil may be independent of gastric antisecretory effects. The correlation of fecal blood loss with gastric lesion score suggests the possibility that either measurement may be used as an indication of gastric lesion occurrence or severity.

Topics: Animals; Anti-Ulcer Agents; Aspirin; Dogs; Female; Gastric Mucosa; Gastrointestinal Hemorrhage; Gastroscopy; Male; Occult Blood; Prostaglandins E; Rioprostil; Stomach Diseases

This study was undertaken to investigate the ability of a cytoprotective synthetic primary alcohol PGE1 analog, rioprostil, to protect the rat gastric mucosa against topically applied 40% (v/v) ethanol. Use of an ex vivo gastric chamber model facilitated correlation of changes in dynamic physiological parameters (PD and net cation fluxes) with changes in mucosal structure. We were particularly interested in defining changes in mucosal structure which accompanied topical application of rioprostil and which might explain subsequent resistance to the effects of ethanol. Topical application of rioprostil for 10 min provided concentration-dependent protection against ethanol-induced hemorrhagic erosions. The most effective dose and concentration tested (25 micrograms rioprostil at a concentration of 10 micrograms/ml) completely prevented ethanol-induced lesion formation. Protection was not accompanied by significant preservation of the interfoveolar epithelium against ethanol, but did involve prevention of vasocongestion and limitation of damage to the superficial epithelium. Complete recovery of physiological parameters indicative of gastric mucosal barrier integrity occurred within 20 min. The most effective concentrations of rioprostil produced extensive subepithelial edema and, concurrently, significant increases in net efflux of sodium ions, decreases in mucosal PD, and loss of mucosal folding.

Topics: Administration, Topical; Animals; Anti-Ulcer Agents; Dose-Response Relationship, Drug; Edema; Ethanol; Female; Gastric Mucosa; Gastrointestinal Hemorrhage; Membrane Potentials; Microscopy, Electron, Scanning; Potassium; Prostaglandins; Prostaglandins E; Rats; Rats, Inbred Strains; Rioprostil; Sodium