Cellular Therapies for Myocardial Infarct Repair

Despite significant advances in prevention, diagnosis,and treatment, myocardial infarction remains the numberone cause of death in the United States and other industrialized nations. Myocardial infarctions almost alwaysresult from complications of atherosclerosis, typicallyarising when an atherosclerotic plaque ruptures, leadingto thrombotic occlusion of a major coronary artery. Myocardium has one of the highest metabolic rates of anytissue in the body, making it very susceptible to injury byischemia (deprivation of blood flow). Irreversible ischemic injury (defined as cell death occurring despitereperfusion) begins within 20 minutes of severe ischemiain vivo in all species studied. A wavefront of cell deaththen progresses from subendocardium to subepicardium(Reimer et al. 1977; Reimer and Jennings 1979). Thetime to completion of irreversible injury varies withspecies, from 1–2 hours in the mouse (Michael et al.1999) to 3–6 hours in the dog (Reimer and Jennings1979). Although cardiac myocytes are the most ischemiasensitive cell population, prolonged ischemia also killsmost of the fibroblasts and vascular cells in the tissue...