Wahaj Aman, Mohammad Hafizullah.
Reperfusion injury - challenges to reduce it.
Pak Heart J Jan ;50(1):1-5.

Reperfusion achieved through pharmacological agents or mechanical angioplasty is associated with reperfusion injury. This implies several events associated with reperfusion, some transitory like reperfusion arrhythmias mostly ventricular arrhythmias and stunning of myocardium and permanent known as lethal reperfusion injury inferring death of myocardium induced by reperfusion. Whereas transitory effects have been accepted and documented, 'lethal reperfusion injury' following reperfusion in STEMI has long been a matter of deliberation. This has been essentially due to lack of definitive clinical demonstration in spite of convincing experimental evidence. There has been a gap between well-defined and controlled experimental models and unclear human proofs - clinical models. 'Lethal reperfusion injury' is defined as a potentially preventable death of myocardium that was viable at the time of reperfusion, which is consequence of events triggered or exaggerated by reperfusion. The fact that preventive maneuvers like post-conditioning limit infarct size without affecting ischemic injury is the best demonstration of the reality of lethal reperfusion injury.The idea of lethal reperfusion injury has since won progressive acceptance on the basis of evidence coming from clinical and basic science studies.4 Lethal reperfusion injury reduction concept was first tested in 2005 showing that ischemic post-conditioning can reduce infarct size in STEMI. In this proof-of-concept trial, ischemic post-conditioning was applied within one minute after reflow by inflating / deflating angioplasty balloon (low-pressure, upstream of the stent) in 4 one-minute cycles. This resulted in a 36%reduction of the area under the curve for creatine kinase release, a surrogate marker of infarct size. Though many but not all, of the small trials performed showed infarct size reduction in patients undergoing post-conditioning. However, the largest randomized clinical trial POST (Effects of Postconditioning on Myocardial Reperfusion in Patients With ST-Segment Elevation Myocardial Infarction) of post-conditioning in STEMI was neutral. Remote ischemic conditioning - conditioning performed in a distant organ has been described as another form of myocardial conditioning well described in animal models. In human scenario remote ischemic pre-conditioning 4 five-minute brachial cuff inflations applied during ongoing STEMI, during ambulance transfer to the PCI center and before PCI reperfusion resulted in increased myocardial salvage compared with regular PCI,with a potential for fewer long-term clinical events.25,26 Over the past decades, important progress has been made in phase II trials evaluating protective interventions against lethal reperfusion injury. The challenge for the future is to design larger trials to evaluate clinical outcomes employing newer therapies to contain lethal reperfusion injury. It is believed that the advances in the next decade will emerge from refining the current day therapies rather that identifying new drugs.

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