THE EFFECT OF PLATELET-ACTIVATING-FACTOR ANTAGONIST TCV-309 ON ARRHYTHMIAS AND FUNCTIONAL RECOVERY DURING MYOCARDIAL REPERFUSION

Background: We investigated the effects of a platelet-activating-facto r antagonist TCV-309, an antagonist of metabolites of ischemia, on arr hythmias and functional recovery during in-situ reperfusion in dogs. M ethods: Open-chest anesthetized dogs were subjected to ligation of the left anterior coronary artery. Ischemia was maintained for 20 min aft er which reperfusion was allowed. A cardiac surface ECG was recorded c ontinuously with the II limb lead. Monophasic action potential, left v entricular segment shortening measured by sonomicrometer, and left ven tricular pressure were recorded simultaneously under atrial pacing (gr oup A, n = 14). In a second group of dogs, TCV-309 (1 mg/kg) was admin istered before coronary artery occlusion (group B, n = 12). The hearts were constantly paced through the right atrium at 120 beats/min throu ghout all experiments. Measurements were continuously obtained from be fore drug administration to 30 min after reperfusion. Results: The 90% repolarization time of monophasic action potentials in group B reveal ed significant recovery compared with group A until the fifth minute a fter reperfusion (P < 0.02). Reduction of severe ventricular arrhythmi as was observed during reperfusion in group B (P < 0.05). The percenta ge segment shortening and left ventricular pressure did not differ sig nificantly between the groups. Conclusion: The platelet-activating-fac tor antagonist had beneficial effects on arrhythmias but not on functi onal recovery during reperfusion after brief coronary artery occlusion in situ in dogs.