Complement and polymorphonuclear leukocyte activation each play a role in determining myocardial ischemia-reperfusion injury

Cobra venom factor (CVF) transiently activates polymorphonuclear leukocytes (PMN) by complement activation, followed by rapid complement depletion and gradual reversal of PMN activation. Utilizing these sequential changes cau sed by CVF, the individual and combined effects of complement and PMNs on m yocardial infarct size (IS) were investigated. Rats were treated with CVF, and/or anti-PMNs. Complement was depleted, but circulating PMNs were being activated at 4h after CVF administration, and at 36h after, complement was depleted, but PMNs were in a near basal condition. Under anesthesia, the ra ts had a 30-min coronary occlusion followed by 6h of reperfusion. The IS wa s assessed by tetrazolium staining. CVF, as well as anti-PMNs, reduced myel operoxidase (MPO) activity in the risk area and the reduced MPO resulted in a reduced IS, which was also the effect of anti-PMNs, but complement deple tion by CVF, during which circulating PMNs were activated, failed to reduce the IS despite low MPO activity. These results suggest that complement and the condition of PMNs each play a role in determining the IS, and ischemic reperfusion injury might be produced even by relatively low myocardial MPO activity.