Effect of Platelet GPIIb/IIIa Receptor Blockade With MK383 on Infarct Size and Myocardial Blood Flow in a Canine Reocclusion Model:

Platelet activation and aggregation during ischemia influence reperfusion-related myocyte necrosis, myocardial perfusion at the microvascular level, and thereby eventual recovery of cardiac performance. Inhibition of platelet activity therefore represents a worthwhile target to reduce cellular injury. The current study examined the effects of MK383 (tirofiban), a potent inhibitor of platelet aggregation, on infarct size and myocardial perfusion in canine subjects to either reocclusion (ie, 120-minute + 60-minute ischemia with intervening reperfusion) or prolonged occlusion (ie, 3 hours) followed by reperfusion (180 minutes). Platelet aggregation, infarct size (tetrazolium staining), coronary blood flow (flow probe), coronary vascular reserve, and myocardial perfusion (microspheres) were evaluated. MK383, administered at the time of reperfusion, produced a modest reduction of tissue necrosis (compared to saline-treated controls) in the reocclusion and prolonged occlusion studies. Blood flow in the infarct-...