The effects of lipoxygenase inhibitor and peptidoleukotriene antagonist on myocardial injury in a canine coronary occlusion-reperfusion model

Abstract

We studied effects of lipoxygenase inhibitor (AA-861) and peptidoleukotriene antagonist (ONO-1078) on infarct size, polymorphonuclear leukocyte (PMNs) infiltration, gross myocardial hemorrhage and ventricular arrhythmias in canine coronary occlusion (2 hr)-reperfusion (5 hr) model. Infarct size (IS) and risk area (RA) were determined by dual staining technique. Thirty minutes before coronary occlusion dogs were randomly assigned to one of the following three groups: lipoxygenase inhibitor group (n=11) receiving AA-861 3 mg/kg i.v., peptidoleukotriene antagonist group (n=11) receiving continuous intravenous infusion of ONO-1078 1 μg/kg/min and vehicle control group (n=15). Both AA-861 and ONO-1078 reduced infarct size [AA-861: 21.8±1.3% of RA (mean±SEM), ONO-1078: 22.5±4.4 % vs Control: 54.0±6.4%, p<0.1 and p<0.01, respectively] and area of gross myocardial hemorrhage (AA-861: 5.1±2.4% of IS, ONO-1078: 5.2±2.5 % vs Control: 22.3±3.9%, p<0.01 and p<0.01, respectively). Both drugs also decreased frequency of ventricular premature contractions both during occlusion and during reperfusion, and that of ventricular tachycardia during reperfusion. AA-861 inhibited PMNs recruitment into infarcted area. However, ONO-1078 had no significant influence on degree of PMNs infiltration. These results suggest that lipoxygenase products, especially peptidoleukotrienes (LTC 4, D 4 and E 4) may play important roles in the pathogenesis of myocardial ischemic and reperfusion injuries.