title: Prostaglandin prevents aspirin injury in the canine stomach under in vivo but not in vitro conditions.
abstract: This study compared the ability of topical 16,16-dimethyl prostaglandin E2 in a dose range of 0.3-3.0 micrograms/ml to prevent aspirin-induced injury in the canine stomach under both in vivo and in vitro conditions. For in vitro studies, isolated strips of oxyntic mucosa were exposed to 10 or 20 mM aspirin (ASA) at pH 1-4, with and without treatment with 16,16-dimethyl prostaglandin E2. For in vivo experiments, a portion of the oxyntic stomach was mounted between the rings of a Lucite chamber, with splenic vessels intact, such that the mucosa was divided into halves. Both sides were exposed to 20 mM ASA at pH 1 or 2, and one side also received concomitant treatment with 16,16-dimethyl prostaglandin E2. After ASA exposure, tissue samples were prepared for quantitative microscopic analysis of the degree of injury. Under both experimental conditions, the magnitude of gastric injury by ASA was pH-related, being most pronounced at pH 1; this damage was worse under in vitro conditions, and both concentrations of ASA were equally damaging in this setting. 16,16-Dimethyl prostaglandin E2 failed to prevent ASA injury in vitro at any pH and ASA concentration tested, but markedly reduced the magnitude of injury in vivo. The most effective protective dose of 16,16-dimethyl prostaglandin E2 under in vivo conditions was 1.0 micrograms/ml. The diminished tolerance to ASA damage in vitro when compared with in vivo, and the inability of 16,16-dimethyl prostaglandin E2 to prevent these damaging effects in vitro, underscores the probable crucial role for blood flow, and possibly neural innervation, in mediating the protective effects of prostaglandins.
authors.affiliation: Department of Surgery, University of Texas Medical School, Houston.
authors.forename: J M
authors.initials: JM
authors.lastname: Henagan
authors.forename: K L
authors.initials: KL
authors.lastname: Schmidt
authors.forename: T A
authors.initials: TA
authors.lastname: Miller
mesh_terms: D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology*; D000818:Animals; D001241:Aspirin / Q000633:toxicity*; D004285:Dogs; D005260:Female; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*; D012039:Regional Blood Flow
chemical_list: D011459:Prostaglandins E, Synthetic; D015064:16,16-Dimethylprostaglandin E2; D001241:Aspirin