Platelet GPIIb/IIIa receptor blockade reduces infarct size in a canine model of ischemia-reperfusion

We studied the effects of N-acetyl-cys-asn-(5,5-dimethyl-4-thiazolidine-carbonyl)-4-amino-methyl-phe-gly-asp-cys, monoacetate (MK-0852) (platelet GPIIb/IIIa receptor blocker) on peak reactive hyperemia, distribution of blood flow, regional contractile function and infarct size in a canine model of acute ischemia-reperfusion injury. BACKGROUND Platelet activation and formation of platelet microaggregates in coronary vessels could contribute to ischemia-induced myocyte injury. Inhibition of platelet aggregation could reduce ischemia-reperfusion injury. METHODS Three groups of dogs (n = 10/group) were studied; group 1-heparin (HEP) (100 U/kg/h intravenously), group 2-MK-0852 (300 mug/kg intravenous bolus followed by 3 mug/kg/min for 3 h) and group 3-MK-0852 plus HEP. Infarct size after 60 min regional ischemia and 3 h reperfusion was evaluated by tetrazolium staining and normalized to risk area (Monastral blue dye). RESULTS Infarct size in HEP-treated controls was 32.4 +/- 2.8%; in MK-0852 without or with HEP groups, infarct size was 17.4 +/- 1.9% (p = 0.001) and 23.4 +/- 3.0% (p = 0.04), respectively. Cardiac hemodynamics and rate-pressure product were comparable between groups. multivariate analysis using collateral blood flow as the independent variable confirmed the cytoprotective actions of MK-0852. Postischemic peak reactive hyperemia in the infarct-related artery was depressed in all groups; during reperfusion, transmural distribution of myocardial blood flow returned to near control levels, but severe regional hypokinesia persisted. CONCLUSIONS Diminished infarct size with MK-0852 treatment suggests an additional mechanism of benefit for GPIIb/IIIa blockers beyond stabilization of a culprit acute coronary lesion. This cytoprotective effect was unrelated to preservation od coronary vasoreactivity (assessed by reactive hyperemia), restoration of blood flow across the myocardium or acute improvement in contractility. (C) 2000 by the American College of Cardiology.