No RISK, no ... cardioprotection? A critical perspective

Early reperfusion is today's gold standard therapy for acute myocardial infarction. The underlying fundamental experiments that demonstrated salvage of myocardial tissue after prolonged coronary occlusion were published less than 4 decades ago1,2 and then subsequently confirmed in large-scale clinical trials such as the GISSI trial and many others. The notion that reperfusion may not only salvage infarcting myocardium but also induce damage itself dates back almost as long.3,4 The awareness of such potential reperfusion injury and the ambivalent character of reperfusion5 prompted the search for strategies to modify reperfusion. Of note, modalities to avoid immediate full restoration of blood flow and to induce more gentle reperfusion were developed;6,7 however, it remained controversial whether6 or not7 gentle reperfusion indeed reduced infarct size after prolonged myocardial ischaemia. As of 1997 there was still no consensus on the existence of lethal reperfusion injury.8 It was not until the detection of the ischaemic postconditioning phenomenon, i.e. the reduction of infarct size following prolonged coronary occlusion by staccato reperfusion with a few cycles of re-occlusion,9 that the existence of lethal reperfusion injury became unanimously accepted.10–13 Ischaemic postconditioning protects from infarction also in humans, … *Corresponding author. Tel: +49 201 723 4480; fax: +49 201 723 4481; E-mail address : gerd.heusch{at}uk-essen.de