C1-INH and its effect on infarct size and ventricular function in an acute pig model of infarction, cardiopulmonary bypass, and reperfusion.
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.
Schreiber
C
C
Clinic for Cardiovascular Surgery, German Heart Center Munich at the Technical University Munich, München, Germany. schreiber@dhm.mhn.de
Heimisch
W
W
Schad
H
H
Brkic
A
A
Badiu
C
C
Lange
R
R
Bauernschmitt
R
R
D000818:Animals; D002315:Cardiopulmonary Bypass; D050718:Complement C1 Inhibitor Protein / Q000627:therapeutic use*; D051056:Complement Inactivating Agents / Q000627:therapeutic use*; D001026:Coronary Artery Bypass; D003326:Coronary Circulation; D004195:Disease Models, Animal; D007430:Intraoperative Care; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D015425:Myocardial Reperfusion; D013552:Swine; D016277:Ventricular Function, Left
D050718:Complement C1 Inhibitor Protein; D051056:Complement Inactivating Agents