Platelet-Activating Factor Acetylhydrolase Prevents Myocardial Ischemia-Reperfusion Injury

Abstract

Background —Platelet-activating factor (PAF) is one of the most potent biological mediators of tissue injury. PAF acetylhydrolase (PAF-AH) is a recently isolated naturally occurring enzyme that hydrolyzes PAF and renders it inactive. We hypothesize that inhibition of PAF with PAF-AH will reduce myocardial ischemia-reperfusion (I/R) injury in vivo. Methods and Results —The coronary ligation model was used in New Zealand white rabbits. The large branch of the marginal coronary artery was occluded for 45 minutes, followed by 2 hours of reperfusion. Fifteen minutes before reperfusion, animals were given either 2 mg/kg of vehicle or of PAF-AH. At the completion of 120 minutes of reperfusion, percentage of necrosis, degree of neutrophil infiltration, and measurements of regional contractility were assessed. Data are expressed as the mean±SEM and compared by Student’s t test or Mann-Whitney ANOVA. Both groups of animals showed an equivalent area at risk; however, 46.7±11% was necrotic in the animal treated with vehicle. In contrast, 20.9±7.0% was necrotic in the animals treated with PAF-AH ( P <0.05). Systolic shortening and wall thickness were significantly greater in those animals treated with PAF-AH at 15, 30, 60, and 120 minutes of reperfusion ( P <0.05). Quantification of neutrophil infiltration showed a 62% reduction in the PAF-AH treated animals compared with those treated with vehicle alone. Conclusions —PAF-AH is a potent cardioprotective agent in an in vivo model of I/R injury.