Abstract
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 1 h of reperfusion to a level that was sustained through 24 h. 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 1 h 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 1 h of reperfusion at a level that is maintained through 24 h. ROS contribute significantly to LPMI during the first 3 h of reperfusion, while complement deposition, which becomes significant after 3-h reperfusion, may contribute thereafter.