Who is the bad guy in myocardial postischemic reperfusion injury?

Abstract

Acute myocardial infarction (AMI) is one of the most prevalent causes of death in the industrialized world. However, up to a third of patients with AMI can achieve spontaneous reperfusion of the infarct-related coronary artery within 24 hours, leading to improved healing of infarcted tissue. Immediate, pharmacologically or mechanically induced reperfusion has improved the prognosis for patients with AMI substantially. Nevertheless, the re-establishment of blood flow to infarcted tissues initiates a number of inflammatory events. Thus, although necessary for the preservation of reversibly injured heart tissue, reperfusion is associated with additional injury.A large body of literature shows that activation of the complement system, including the generation of C5a – which mediates the influx of neutrophils – and deposition of the lytic terminal complement complex, occurs after ischemia and reperfusion. Specific inhibitors of different complement components have been shown to be cardioprotective in models of reperfusion injury, indicating that pharmacological manipulation of the complement system might be a feasible strategy to improve the outcome of reperfusion therapy. However, it is still debated which complement pathway triggers complement activation after ischemia and reperfusion.Jordan et al. [1xInhibition of mannose-binding lectin reduces postischemic myocardial reperfusion injury. Jordan, J.E. et al. Circulation. 2001; 104: 1413–1418Crossref | PubMedSee all References[1] provide strong evidence that the newly discovered lectin complement-activation pathway might be important in the pathophysiology of postischemic reperfusion injury. The central recognition molecule in this pathway is mannose-binding lectin (MBL), which is believed to play an important role in innate immune defense. Using monoclonal antibodies that inhibit the activity of rat MBL specifically, the authors show that complement deposition and the expression of several proinflammatory genes were attenuated greatly in myocardial ischemic tissue from rats subjected to coronary artery occlusion followed by a period of reperfusion. Of significant interest was the observation that the inhibition of MBL resulted in a 39% reduction of the infarct size and 47% reduction in the influx of neutrophils compared with controls. This indicates that during postischemic reperfusion, endogenous MBL ligands are exposed. These results shed new light on the initiating events occurring in postischemic reperfusion injury and suggest that the inhibition of MBL has the potential to improve the outcome of revascularization after AMI.