EFFECT OF PLATELET-ACTIVATING-FACTOR ANTAGONIST L-691,880 ON LOW-FLOWISCHEMIA-REPERFUSION INJURY OF THE LARGE COLON IN HORSES

Objective-To determine the effect of platelet-activating factor (PAF) antagonist L-691,880 on low-flow ischemia and reperfusion (I-R) of the large colon in horses. Animals-12 adult horses. Experimental Design-H orses were anesthetized, and the large colon was exteriorized through a ventral median celiotomy and instrumented. Colonic arterial blood fl ow was reduced to 20% of baseline (BL) and maintained for 3 hours; flo w was then restored, and the colon was reperfused for 3 hours. One of two solutions was administered intravenously 30 minutes before reperfu sion: group 1, 10 mL/kg 0.9% NaCl; and group 2, 5 mg/kg PAF antagonist L-691,880 in 0.9% NaCl. Hemodynamic variables were monitored and reco rded at 30-minute intervals. Systemic arterial and colonic venous bloo d were collected for measurement of blood gas tensions, oximetry analy ses, packed cell volume, and total plasma protein concentrations. Colo nic venous blood was collected for determination of lactate, 6-keto pr ostaglandin F-1 alpha (6-kPG), prostaglandin E-2 (PGE(2)), and thrombo xane B-2 (TXB2) concentrations. Full-thickness biopsy specimens were h arvested from the left ventral colon for histological evaluation. Resu lts-There were no significant differences between the two groups for a ny hemodynamic or metabolic variables. Colonic venous pH decreased, an d carbon dioxide tension and lactate concentration increased during is chemia but returned to BL values during reperfusion. Colonic venous 6- kPG Concentration was significantly increased above BL value at 2 hour s and remained increased through 6 hours in horses of both groups. Col onic venous PGE(2) concentration was significantly greater in group 2 compared with group 1 throughout the study. Colonic venous PGE(2) conc entration was increased above BL value from 3 to 6 hours in horses of both groups. Colonic venous TXB2 concentration was not different betwe en groups but was significantly increased above the BL value for the f irst hour of reperfusion. Low-flow I-R of the large colon caused signi ficant mucosal necrosis, hemorrhage, edema, and neutrophil infiltratio n; however, there were no differences in histological variables betwee n vehicle-control and PAF antagonist-treated horses. Conclusion-No pro tective effects of PAF antagonist L-691,880 were observed on colonic m ucosa associated with low-flow I-R. Additionally, deleterious drug-ind uced effects on hemodynamic and metabolic variables and colonic mucosa l injury were not observed. (C) Copyright 1998 by The American College of Veterinary Surgeons.