Pharmacological protection of reperfusion injury in ST-segment elevation myocardial infarction. Gone with the wind?

Primary percutaneous coronary intervention (PCI) represents the greatest progress in the treatment of ST-elevation myocardial infarction (STEMI) over the last 30 years. It reduces infarct size with an early restoration of blood flow within an ischemic myocardium. However, it is associated with a still partly mysterious paradox: reperfusion injury [1]. It is characterized by reversible mechanical dysfunction called “myocardial stunning” and microvascular obstruction or the “no reflow phenomenon” which corresponds to the presence of capillary damage, endothelial cell swelling, intraluminal thrombosis and injured cardiomyocytes. Several mediators are involved in ischemia/reperfusion injury; on one hand prolonged ischemia causes pH alterations, activation of anaerobic metabolism, dysfunction of ATPase-dependent ion transport mechanisms, intracellular calcium overload, cell swelling and finally cell death. On the other hand, after reperfusion, there is an increase of reactive oxygen species and tissue infiltration of neutrophils and pro-inflammatory cytokines with paradoxical exacerbation of the ischemic injury. Consequently, at the clinical level, reperfusion injury is associated with residual large infarct size, impaired left ventricular ejection fraction, ventricular arrhythmias and poor prognosis [1]. Figure 1 shows infarct size and its changes with reperfusion and prevention of reperfusion injury.
Therefore, combating reperfusion injury remains one of the most interesting and challenging frontiers in STEMI management. With the aim of mitigating the risk of ischemic-reperfusion injury in this setting several strategies have been proposed. Table I shows the major recent studies investigating reperfusion injury. Several studies have analyzed ischemic post-conditioning (IPoC) in animal models, with very promising results. It is a technique of cardiac protection in which repeated brief interruptions of blood flow are performed before restoring final myocardial reperfusion, improving myocardial metabolic recovery [1, 2]. On the wave of these pre-clinical findings, the largest IPoC trial in STEMI patients so far, the recent Third Danish Study of Optimal Acute Treatment of Patients With ST-elevation Myocardial Infarction-Ischemic Postconditioning (DANAMI-3-iPOST), failed to demonstrate that routine IPoC reduces the composite endpoint of all-cause death and hospitalization for heart failure at a median follow-up of about 3 years [2]. These results have been...


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