Sublytic complement attack reduces infarct size in rabbit isolated hearts: evidence for C5a-mediated cardioprotection

Sublytic complement attack can elicit protective cellular responses without precipitating cell death. Our investigation examined the effects of non-lethal complement activation in isolated hearts. New Zealand white rabbit hearts were subjected to 30 min of ischemia followed by 1 h of reperfusion. Prior to ischemia, hearts were perfused for 20 min with 0.5% normal human plasma (NHP). Hearts treated with NHP developed significantly (p<0.05) smaller infarcts compared with controls, expressed as percent of area at risk (AAR) (25.3+/-4.0% vs. 40.9+/-4.3%, respectively). Heat-inactivation, soluble complement receptor 1 (sCR1; 20 nM), and anti-C5a antibody reversed the protective effect of NHP (39.0+/-3.1%, 41.7+/-5.1% and 38.4+/-2.3% AAR, respectively). Hearts treated with 3 nM C5a exhibited infarct sizes similar to those exposed to NHP (27.6+/-5.0% AAR). sCR1 alone did not affect infarct size (37.9+/-4.5% AAR). The results suggest that non-lethal complement activation attenuates reperfusion injury through formation of C5a.