Mechanism of reperfusion damage after thrombolysis and ‘direct PTCA’

Abstract

Summary There is general agreement between cardiologists, that reperfusion of the infarct related coronary artery (PTCA) is the method of choice for the treatment of an acute myocardial infarction. However, the method utilized for inducing a rapid and complete reperfusion is still discussed. Even if thrombolysis will remain the method of choice for the major part of the population, part of the patient cohort with acute infarction will be treated by direct PTCA. Rapid reperfusion of ischemic myocardium reduces infarct size by limiting infarct extension into the entire area at risk, although a reperfusion damage is induced in the core ischemic area. This reperfusion damage has been convincingly shown to occur in experimental animals; however, in the clinical setting attempts to quantify this deleterious side-effect of reperfusion strategies exactly has not been successful. Thus, for studying factors involved in reperfusion, for example, activation of the complement cascade, animal models of myocardial ischemia and reperfusion had to be involved. From clinical and experimental studies it was known, that complement activation occurs during myocardial ischemia and reperfusion, being markedly enhanced if reperfusion was due to thrombolytic therapy. The role of complement activation in infarct size enlargement was studied in a pig model of acute reperfusion and a rat model of chronic reperfusion with the help of a C1-esterase inhibitor, suppressing activation of the classical pathway of complement activation. In both animal models a marked cardioprotective effect of C1-esterase inhibitor treatment was detected, characterized by a significant infarct size reduction, diminished leukocyte infiltration and reduced adhesion molecule expression. Thus, complement-activation and complement-dependent leukocyte stimulation, and tissue damage may be involved in inducing injury during reperfusion therapy of ischemic myocardium. If the inhibition of complement activation represents a successful method for reducing ischemic injury and reperfusion damage in human myocardial infarction treated by thrombolysis or direct PTCA still has yet to be determined in clinical studies in the future.