Effect of platelet-activating factor antagonist L-691,880 on low-flow ischemia-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: Horses were anesthetized, and the large colon was exteriorized through a ventral median celiotomy and instrumented. Colonic arterial blood flow was reduced to 20% of baseline (BL) and maintained for 3 hours; flow was then restored, and the colon was reperfused for 3 hours. One of two solutions was administered intravenously 30 minutes before reperfusion: 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 recorded at 30-minute intervals. Systemic arterial and colonic venous blood were collected for measurement of blood gas tensions, oximetry analyses, packed cell volume, and total plasma protein concentrations. Colonic venous blood was collected for determination of lactate, 6-keto prostaglandin F1 alpha (6-kPG), prostaglandin E2 (PGE2), and thromboxane B2 (TXB2) concentrations. Full-thickness biopsy specimens were harvested from the left ventral colon for histological evaluation. RESULTS: There were no significant differences between the two groups for any hemodynamic or metabolic variables. Colonic venous pH decreased, and carbon dioxide tension and lactate concentration increased during ischemia but returned to BL values during reperfusion. Colonic venous 6-kPG concentration was significantly increased above BL value at 2 hours and remained increased through 6 hours in horses of both groups. Colonic venous PGE2 concentration was significantly greater in group 2 compared with group 1 throughout the study. Colonic venous PGE2 concentration was increased above BL value from 3 to 6 hours in horses of both groups. Colonic venous TXB2 concentration was not different between groups but was significantly increased above the BL value for the first hour of reperfusion. Low-flow I-R of the large colon caused significant mucosal necrosis, hemorrhage, edema, and neutrophil infiltration; however, there were no differences in histological variables between vehicle-control and PAF antagonist-treated horses. CONCLUSION: No protective effects of PAF antagonist L-691,880 were observed on colonic mucosa associated with low-flow I-R. Additionally, deleterious drug-induced effects on hemodynamic and metabolic variables and colonic mucosal injury were not observed.