Recombinant human complement C5a receptor antagonist reduces infarct size after surgical revascularization

Abstract Objectives: This study tested the hypothesis that a recombinant human C5a antagonist, CGS 32359, attenuates neutrophil activation and reduces infarct size in a porcine model of surgical revascularization. Methods: CGS 32359 (0.16-16 μmol/L) dose-dependently inhibited superoxide production by human C5a-activated porcine neutrophils (18 ± 3.7 vs 1.6 ± 0.5 nmol/5 min/5 × 10 6 neutrophils; P 2 ( P –1 · h –1 ), or CGS 32359 (CGS, n=7, 60 mg/kg bolus, 60 mg · kg –1 · h –1 ) was infused. After ischemia, 1-hour arrest was achieved by means of multidose hypothermic (4°C) blood cardioplegia, followed by 2.5 hours of off-bypass reperfusion. The ligature on the left anterior descending artery was released before the second infusion of cardioplegic solution. Results: Area at risk was similar in all groups (saline solution, 27% ± 2%; mannitol-buffer vehicle, 26% ± 2%; CGS, 26% ± 2% left ventricular mass). Infarct size (area necrosis/area at risk) was significantly reduced by CGS (18% ± 6%, P P Conclusions: We conclude that the recombinant human C5a receptor antagonist CGS 32359 inhibits surgical ischemia-reperfusion injury after coronary occlusion. (J Thorac Cardiovasc Surg 2000;120:350-8)