Impact of cellular mechanisms of ischemia on CABG failure

Abstract

Since its introduction in clinical practice in the early 1960s, coronary artery bypass graft (CABG) surgery has evolved steadily, and nowadays represents the major therapeutic option for coronary artery disease (CAD) with multivessel involvement, unprotected left main coronary disease, left ventricular dysfunction, or for patients with diabetes mellitus, where CABG results are superior to percutaneous interventions with drug-eluting stents. Despite major progress in surgical techniques and in the prevention or treatment of postoperative complications, the incidence of these complications remains elevated, partly due to complexity, advanced stage CAD, and co-morbidity in patients subjected to this type of intervention. A good understanding by clinicians of the intricate pathophysiology processes at cellular and molecular level associated with myocardial ischemia and its consequences, like apoptotic or oncotic cell death, fi brosis and ventricular remodeling, revascularization, neointimal proliferation in vascular grafts, is a prerequisite for a fruitful application of novel experimental therapies, such as bone marrow hematopoietic cells or mesenchymal stem cells, gene therapies or micro-RNA antisense sequences aiming to improve revascularization, limit cellular apoptosis and fi brosis, and promote redifferentiation to cardiomyocytes of mature cells like fi broblasts. A particular emphasis has been placed on sensitive topics such as myocardial stunning, hibernation, ischemic pre- and post-conditioning, and pharmacological approaches to apoptosis and neointimal proliferation in vascular grafts.