Cardioprotective effects of abciximab (ReoPro(R)) in an isolated perfused rat heart model of ischemia and reperfusion

Abstract

Ischemia followed by reperfusion in the presence of polymorphonuclear leukocytes (PMNs) results in cardiac contractile dysfunction as well as myocardial injury, due in large part to endothelial dysfunction, upregulation of cell adhesion molecules and subsequent neutrophil induced cardiac injury. We studied the effects of abciximab (ReoPro), an anti-IIb/IIIa antibody, which has been shown to attenuate platelet interactions, in a neutrophil-platelet mediated isolated perfused rat heart model of ischemia (I) (20 min) and reperfusion (R) (45 min). Administration of abciximab (6.5 micrograms/kg) 10 min prior to the perfusion of the PMN + platelet perfused I/R heart improved post-reperfusion coronary flow and preserved post-reperfusion left ventricular developed pressure (LVDP) and +dP/dt max as indices of cardiac contractile function. Abciximab-treated hearts reperfused in the presence of PMNs and platelets preserved all indices of cardiac contractile function. I/R heart perfused with PMNs and platelets produced a profound injury to the hearts which was attenuated with the treatment of abciximab. In addition, abciximab significantly reduced PMN accumulation in the ischemic myocardium from 38 +/- 1 PMNs/mm2 in untreated hearts to 7 +/- 1 in rats given abciximab. Similar results were obtained with PMN perfused I/R rat hearts without platelets. These results provide evidence that abciximab is a potent and effective cardioprotective agent that inhibits leukocyte-endothelial cell interactions as well as platelet-endothelial cell interaction and preserves cardiac contractile function and coronary perfusion following myocardial ischemia and reperfusion. Therefore, IIb/IIIa may be important in attenuating both platelet and neutrophil-mediated myocardial dysfunction.