Angioplasty improves mortality in the managment of acute coronary syndrome in patients with chronic anaemia

Abstract

Cardiac protection is a broad term that refers to all strategies aimed at the attenuation of the damage caused by myocardial ischaemia (MI) and reperfusion. The term is used both in the experimental and clinical field, embracing a very wide (too wide in fact!) range of conditions from reduction of coronary atherosclerosis progression to an immediate reduction of the myocardial infarct size due to acute ischaemia and/or reperfusion. There is no doubt that cardiac protection is a story of broad success but there are also some failures. Indeed, the progression of coronary atherosclerosis can be reduced with angiotensin II inhibitors and statins with a consequential improvement of outcome. Equally, after the demonstration that coronary thrombosis is the cause and not the result of MI, timely restoration of blood flow (reperfusion) has become the standard treatment for these patients, with a corresponding limitation of infarct size, long-term improvement of MI and, more importantly, a reduction in mortality. Despite this success, however, the process of late restoration of blood flow to the ischaemic myocardium can paradoxically induce injury, a phenomenon known as reperfusion injury (RI). Therefore, the major challenge of cardiac protection today is to reduce RI. The problem is that RI is a complex phenomenon, involving many unclearly defined players, all contributing to the final damage that is inflicted on the heart. RI was originally described as a cell swelling, hyper-contracture or disruption of the intra-cellular structure and, in time, has progressed to at least four other types of cardiac dysfunction such as: myocardial stunning, the no-reflow phenomenon, reperfusion arrhythmias and finally lethal reperfusion injury described as an independent mediator of cardiomyocyte death (either necrosis, apoptosis, autophagy or necroptosis), different from ischaemic injury. Several approaches to reduce RI were tried with antioxidants, aderosine, beta and CA2+ blockers, statins, glucose with or without insulin and K, Trimetazidine, cyclosporine and other inhibitors of the Ca2+ pore – all without success. Recently, non-pharmacological interventions have also been proposed to reduce RI, mainly pre and post conditioning. The ideas come from the experimental laboratory, showing that brief cycles of ischaemia and reperfusion performed before a prolonged coronary occlusion or after reperfusion reduced infarct size in dogs. However, when applied to the clinic (mainly post-conditioning as pre-conditioning is difficult) protocols produced good results in small, proof of concept trials but not in a large randomised clinical trial.