Optimization of microvascular reperfusion in acute myocardial infarction

Variations in flow within the spectrum of Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow determine the recovery of contractile function in the infarct zone after acute myocardial infarction (MI). The limitation of microvascular reperfusion associated with such impairment may be attributable to a variety of factors, including distal embolization of small platelet aggregates and direct interactions among platelets, leukocytes and the endothelium. Activated platelets adhere to the endothelium and modulate chemotactic and adhesive properties of endothelial cells; they also bind with leukocytes and induce up-regulation of the Mac-1 integrin, promoting endothelial adherence and elaboration of inflammatory cytokines. Mac-1 activity and platelet-leukocyte interactions are increased in patients with acute MI. The platelet glycoprotein IIb/IIIa receptor inhibitor abciximab may improve microcirculatory function by reducing distal embolization of platelet aggregates and decreasing platelet-leukocyte interactions. Recent studies in patients undergoing coronary stenting for acute MI have demonstrated that abciximab is associated with significant decreases in platelet-leukocyte interactions and Mac-1 expression compared with standard heparin. In a randomized trial of abciximab versus standard heparin in acute MI patients undergoing stenting, abciximab treatment was associated with significant improvements in peak flow velocity and measures of contractile function, including wall motion index and numbers of hypokinetic chords in the infarct zone and global ejection fraction. These benefits were accompanied by a significant reduction in early cardiovascular events. In addition to maintaining large-vessel patency, abciximab improves recovery of microcirculatory perfusion and contractile function in acute MI.