C1-INH and its effect on infarct size and ventricular function in an acute pig model of infarction, cardiopulmonary bypass, and reperfusion

Thorac Cardiovasc Surg. 2006 Jun;54(4):227-32. doi: 10.1055/s-2006-923947.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiopulmonary Bypass*
  • Complement C1 Inhibitor Protein / therapeutic use*
  • Complement Inactivating Agents / therapeutic use*
  • Coronary Artery Bypass*
  • Coronary Circulation
  • Disease Models, Animal
  • Intraoperative Care
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology
  • Myocardial Reperfusion*
  • Swine
  • Ventricular Function, Left

Substances

  • Complement C1 Inhibitor Protein
  • Complement Inactivating Agents