Review Paper: Pathophysiology of Myocardial Reperfusion Injury: The Role of Genetically Engineered Mouse Models

Abstract

Coronary heart disease is the leading cause of death worldwide, affecting millions of men and women each year. Following an acute myocardial infarction, early and successful reperfusion therapy with thrombolytic therapy or primary percutaneous coronary intervention plays an important role in minimizing tissue injury associated with cessation of blood flow. The process of restoring blood flow to the ischemic myocardium, however, can induce additional injury. This phenomenon, termed myocardial ischemia-reperfusion (MI-R) injury, can paradoxically reduce the beneficial effects of myocardial reperfusion. MI-R injury is characterized by the formation of oxygen radicals upon reintroduction of molecular oxygen to the ischemic tissue, resulting in widespread lipid and protein oxidative modifications, mitochondrial injury, and cell death. In addition, studies have shown that MI-R is characterized by an inappropriate immune response in the microcirculation, resulting in leukocyte-endothelial cell interactions mediated by the upregulation of both leukocyte and endothelial cell adhesion molecules. Furthermore, MI-R ameliorates the production of certain cardioprotective factors such as nitric oxide. Advances in the generation of genetically modified mouse models enable researchers to identify the functional importance of genes involved in these processes.