Microvascular obstruction: The no-reflow phenomenon in animal models of myocardial ischemia and reperfusion

Abstract

In animal models of coronary artery occlusion and reopening of the -epicardial artery, perfusion defects within the area at risk may develop during reperfusion despite complete reopening of the epicardial artery. These anatomical areas of no-reflow are confined to areas of myocardial necrosis and substantially expand during ongoing reperfusion. This reperfusion injury at the microvascular level may be related to ultrastructural alterations of the microvasculature, production of reactive oxygen species during reperfusion, leukocyte accumulation, and release of vasoconstrictive agents. Myocardial infarct size appears to be the major determinant of no-reflow, and cardioprotective interventions leading to smaller infarcts result in reduced microvascular obstruction in most of the models. Several therapeutic strategies have been developed to reduce no-reflow; however, in most of these investigations it was difficult to dissociate no-reflow from infarct size. Transfer to the clinical setting of myocardial infarction shows many similarities, but additional mechanisms such as coronary microembolization significantly contribute to clinical no-reflow.