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-car bonyl)-4-amino-methyl-phe-gly-asp-cys, monoacetate (MK-0852) (platelet GPII b/IIIa receptor blocker) on peak reactive hyperemia, distribution of blood flow, regional contractile function and infarct size in a canine model of a cute ischemia-reperfusion injury. BACKGROUND Platelet activation and formation of platelet microaggregates in coronary vessels could contribute to ischemia-induced myocyte injury. Inhi bition 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 bo lus 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 t etrazolium 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-press ure product were comparable between groups. multivariate analysis using col lateral blood flow as the independent variable confirmed the cytoprotective actions of MK-0852. Postischemic peak reactive hyperemia in the infarct-re lated artery was depressed in all groups; during reperfusion, transmural di stribution of myocardial blood flow returned to near control levels, but se vere regional hypokinesia persisted. CONCLUSIONS Diminished infarct size with MK-0852 treatment suggests an addi tional mechanism of benefit for GPIIb/IIIa blockers beyond stabilization of a "culprit" acute coronary lesion. This cytoprotective effect was unrelate d to preservation od coronary vasoreactivity (assessed by reactive hyperemi a), restoration of blood flow across the myocardium or acute improvement in contractility. (C) 2000 by the American College of Cardiology.