Lethal myocardial reperfusion injury: a necessary evil?

Despite being the most effective means of limiting infarct size, coronary reperfusion comes at a price and induces additional damage to the myocardium. Lethal reperfusion injury (death of myocytes that were viable at the time of reperfusion) is an increasingly acknowledged phenomenon. There are many interconnected mechanisms involved in this type of cell death. Calcium overload (generating myocyte hypercontracture), rapid recovery of physiological pH, neutrophil infiltration of the ischemic area, opening of the mitochondrial permeability-transition-pore (PTP), and apoptotic cell death are among the more important mechanisms involved in reperfusion injury. The activation of a group of proteins called reperfusion injury salvage kinases (RISK) pathway confers protection against reperfusion injury, mainly by inhibiting the opening of the mitochondrial PTP. Many interventions have been tested in human trials triggered by encouraging animal studies. In the present review we will explain in detail the main mechanism involved in reperfusion injury, as well as the various approaches (pre-clinical and human trials) performed targeting these mechanisms. Currently, no intervention has been consistently shown to reduce reperfusion injury in large randomized multicenter trials, but the research in this field is intense and the future is highly promising.