C1-INH and its Effect on Infarct Size and Ventricular Function in an Acute Pig Model of Infarction, Cardiopulmonary Bypass, and Reperfusion

Abstract

Background: Recent studies suggest that complement inhibition reduces reperfusion injury. A clinical setting with local application of a C1 esterase inhibitor (C1-INH) has been modeled in an animal study in order to further investigate these findings. Methods: In 21 pigs, the left anterior descending coronary artery (LAD) was occluded distally to the first diagonal branch for 2 hours (h), including 1 h of cardioplegic arrest during CPB. After release of the coronary snare, C1-INH or NaCl (control) was applied to the aortic root. Thereafter, the aortic cross-clamp was removed and the heart was reperfused for 30 minutes before weaning from CPB. Left ventricular pressure volume analysis was performed by a multielectrode conductance catheter and the area at risk and infarct size were determined from excised hearts. Results: The following data were observed (mean ± SEM) for the control group and the C1-INH group, respectively, after 1-h ligation of the LAD: heart rate (HR) 86 ± 3 and 93 ± 6 beats/min, stroke volume (SV) 1.2 ± 0.1 and 1.2 ± 0.1 ml/kg, aortic pressure (AoP) 83 ± 6 and 87 ± 5 mmHg, left ventricular end-diastolic pressure (LVedP) 12 ± 1 and 11 ± 2 mmHg; two hours after weaning from CPB: HR 106 ± 9 and 123 ± 4 beats/min, SV 0.9 ± 0.1 and 0.9 ± 0.1 ml/kg, AoP 65 ± 5 and 79 ± 7 mmHg, LVedP 9 ± 1 and 8 ± 1 mmHg. Conductance catheter measurements showed no improved left ventricular performance after C1-INH application. Infarct size to area at risk ratio was 61.5 ± 4.2 % for controls and 61.4 ± 4.8 % for C1-INH. Conclusions: Intracoronary application of complement inhibitor in an acute infarction model, which mimicked a clinical setting of urgent coronary bypass grafting after ischemia, has been shown to neither influence the area of infarction, nor the ventricular function.

Infarction - reperfusion - complement inhibition - cardiopulmonary bypass

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