Myocardial Reperfusion Injury

Around the world, and especially in the Western Society, cardiovascular diseases remain one of the leading causes of death.(1) Within the broad range of cardiovas-cular diseases, the proportional burden of ischemic heart disease is especially high within the Middle East, North America, Australia, and the majority of Europe.(2) In the Netherlands, cardiovascular diseases have been the leading cause of death until 2007, with an annual mortality number of over 38,000 cases each year.(3) In 2010, 39,735 (30%) of the 136,058 deaths in the Netherlands were related to cardiovascular diseases, of which 6,823 (17%) cases were caused by acute myocardial infarction (MI). (4) Emergent coronary revascularization by percutaneous coronary intervention (PCI) has significantly reduced early mortality rates and improved prognosis in patients with ST-segment elevation myocardial infarction (STEMI).(5) In some patients, the epicardial flow remains hampered after reperfusion, an angiographic phenomenon commonly known as 'no reflow' and associated with a diminished myocardial salvage, larger infarct size, worse residual LV function and increased mortality.(6;7) Additionally, studies showed that even with complete restoration of epicardial flow, a large proportion of patients have persistent ST-segment elevation, indicating ongoing ischemia and infarction of the myocardium.(8) All these patients have an impaired myocardial reperfusion and are at risk of having more severe myocardial infarctions with left ventricular maladaptive remodelling and more long-term morbidity and mortality.(9;10) Despite the decrease in early mortality due to acute MI, the paradoxical increase in patients with chronic heart failure continues to be a large burden on healthcare systems and society in general. Animal models of myocardial infarction have shown that 20 minutes after reperfusion, areas of reperfusion injury contain capillaries plugged by erythrocytes, platelets and fibrin thrombi, and swollen intraluminal endothelial protrusions, leading to further obstruction of the capillaries(11) and the formation of microthrombi.(12;13) These microthrombi, together with embolization of atherosclerotic debris, are thought to play an important role in the development of the no reflow phenomenon and the development of reperfu-sion injury. Many therapeutic approaches have already been tried, with varying results. Thrombus aspiration during PCI may reduce the burden of atherosclerotic debris in the microcirculation, but the effects on morbidity and mortality remain discussed.(14;15) Adjuvant treatment regimens with vasodilator agents such as adenosine showed promising results in small randomized controlled trials, but failed to show a clear clinical benefit in larger trials.(16;17) Currently, studies are focusing on cardioprotection with specific cardioprotective drugs (e.g. nicorandil, cyclosporine), hyperoxemic reperfusion and myocardial …