Loss of plasma membrane integrity, complement response and formation of reactive oxygen species during early myocardial ischemia/reperfusion

•LPMI was present at 1h of myocardial reperfusion and continued through 24h.•Reactive oxygen species contributed to LPMI during the first 3h of reperfusion.•Complement deposition was not significant until 3h of reperfusion. Loss of plasma membrane integrity (LPMI) is a hallmark of necrotic cell death. The involvement of complement and ROS in the development of LPMI during the early stages of murine myocardial ischemia–reperfusion injury was investigated. LPMI developed within 1h of reperfusion to a level that was sustained through 24h. C3 deposition became significant at 3-h reperfusion and thus contributed little to LPMI prior to this time. SOD1 transgenic mice had significantly less LPMI compared with WT mice at 1h of reperfusion but not at later time points. Catalase transgenic mice were not protected from LPMI at 1-h reperfusion compared with WT mice, but had 69% less LPMI at 3-h reperfusion. This protection was transient. At 24-h reperfusion the LPMI of catalase transgenic mice was identical to that of WT mice. The delayed benefits of over-expressed catalase compared with SOD1 are consistent with its antioxidant action downstream of SOD1. The onset of LPMI occurs within 1h of reperfusion at a level that is maintained through 24h. ROS contribute significantly to LPMI during the first 3h of reperfusion, while complement deposition, which becomes significant after 3-h reperfusion, may contribute thereafter.