Ischemic postconditioning: a clinical perspective

Acute myocardial infarction is a major cause of death and heart failure in western society [1]. Introduction of reperfusion therapy in terms of thrombolysis and primary percutaneous coronary intervention (PPCI) has lead to a significant decreases in morbidity and mortality [2]. Today, PPCI is the recommended therapy for patients with ST-segment elevation myocardial infarction (STEMI). However, generation of reperfusion is a double-edged sword because it has the potential to cause additional myocardial damage not caused by the ischemic insult. This injury occurs in the first minutes of reperfusion and is termed reperfusion injury [3]. Ever since the discovery of reperfusion injury, this damage has been a target of intensive investigation. The patho genesis is very complex and not fully understood. In a clinical perspective, the reperfusion injury appears to be important because it has been suggested to account for as much as 50% of the final myocardial infarct size [4]. Consequently, it is highly relevant to look for means to protect the heart during the reperfusion phase, and ischemic postconditioning (IPost), defined as repetitive interruptions of the coronary blood flow applied after a period of ischemia, is one of the most promising methods. This article focuses on IPost and aims to give an understanding of IPost and a discussion of potential clinical applications during PPCI. Finally, this article will give a brief look into alternative cardioprotective treatments and future perspectives. Cardiomyocyte death: a central element of reperfusion injury It is beyond the scope of the present article to discuss in detail the pathogenesis of reperfusion injury, which has been reviewed comprehensively elsewhere [4–7]. Briefly, reperfusion injury is a syndrome comprising several distinct pathophysiological components: a (reversible) myocardial contractility impairment (stunning), arrhythmias, no-ref low and cardiomyocyte death (the lethal component) [4]. No-reflow may contribute to the lethal component (necrosis and apoptosis) of the reperfusion injury synd rome [8]. However, extensive experimental evidence implicates a number of factors as responsible for the cardiomyocyte death during reperfusion independently of no-reflow (see the following section on cardioprotective mechanisms).