Invited Speaker

Myocardial Reperfusion Injury: an Emerging Field for Drug Therapy in Cardiovascular Disease
David Garcia-Dorado
Spain

Cardiovascular disease is the first cause of death and loss of quality of life in the whole world population, and is expected to continue occupying this position in 2025. This huge social and sanitary impact is mainly due to myocardial cell death occurring during acute coronary syndromes with elevation of the ST segment in the ECG (STEMI). Despite optimal delivery of the most advanced reperfusion therapies, the vast majority of patients with STEMI end up with extensive areas of myocardial necrosis. In this context, treatments able to enhance reperfusion-induced myocardial salvage appear as a new frontier in the treatments of patients with on-going acute myocardial infarction. During the last decades, extensive experimental evidence of the existence and relevance of reperfusion-induced cell death (lethal reperfusion injury) has been developed, its mechanisms have been elucidated to a large extent, and interventions able to limit infarct size when applied at the time of reperfusió have been devised. However, translation of these interventions to clinical practice is very incipient; only ischemic postconditioning, adenosine, atrial natriuretic peptides, and cyclosporine have yielded positive results in clinical trials in patients with STEMI receiving reperfusion therapy. To incorporate cardioprotective treatments against reperfusion injury into clinical guidelines important questions have to be solved, including the lack of basic knowledge (as the molecular structure of the mitochondrial permeability transition pore (MPTP) or the pathway between MPTP opening and immediate sarcolemmal rupture), the existence of orphan targets or specific drugs (as Na/Ca2+ exchanger, calpains, connexines or MPTP inhibitors), and the absence of large morbidity mortality trials. This can be successfully accomplished only through a large cooperative effort in translational research with participation of the laboratory and clinical researchers, the industries, and public research funding agencies.