Effects of flunixin meglumine on short circuit current in equine colonic mucosa in vitro.

Abstract

OBJECTIVES: To study the effect of flunixin meglumine on short circuit current (Isc) in equine right ventral colon in vitro. SAMPLES: Intestinal mucosa from healthy horses and ponies. PROCEDURE: Isc was measured in mucosa from the right ventral colon mounted in Ussing chambers. In experiment 1, collection and incubation solutions were: control (no additions); flunixin meglumine, 4 micrograms/ml; indomethacin, 10(-6) M; and flunixin meglumine (4 micrograms/ml) with 10(-6) M prostaglandin E2. In experiment 2, incubation conditions were: control [plain Krebs-Ringer bicarbonate [KRB] solution]; flunixin meglumine, 4 micrograms/ml in KRB; chloride-free buffer solution; flunixin meglumine (4 micrograms/ml) in a chloride-free buffer solution; and plain KRB with 10(-6) M prostaglandin E2. In experiment 3, tissue from 3 groups (n = 6 each) of animals: controls, physiologic saline solution given IV at 10 minutes before euthanasia; flunixin meglumine (1.1 mg/kg of body weight, IV) given at 10 minutes before euthanasia; and treatment similar to controls, except that tissues were incubated with 8 micrograms of flunixin meglumine/ml of bathing medium. RESULTS: Flunixin meglumine and indomethacin reduced Isc to approximately a third of control current (P < 0.05), but coincubation with flunixin meglumine and 10(-5) M prostaglandin E2 restored Isc close to the control value. Incubation with 10(-6) M prostaglandin E2 alone did not change Isc. When chloride was substituted with isethionate, flunixin meglumine had no effect on Isc. Flunixin meglumine given before euthanasia or included at a concentration of 8 micrograms/ml in all tissue preparation and incubation solutions reduced Isc (P < 0.05). CONCLUSIONS: Flunixin meglumine given IV or added to bathing solutions decreased Isc in equine right ventral colon by a mechanism that appeared to involve prostaglandin-mediated chloride secretion. CLINICAL RELEVANCE: Our results suggest that flunixin meglumine given IV to horses at recommended doses could alter putative effects of colonic prostaglandins.