Total complement inhibition - An effective strategy to limit ischemic injury during coronary revascularization on cardiopulmonary bypass

Background-Activation of complement during revascularization of ischemic myocardium accentuates myocardial dysfunction. Soluble human complement receptor type 1 (sCR1) is a potent inhibitor of complement, as are heparin-bonded (HB) cardiopulmonary bypass (CPB) circuits. This study sought to determine whether total complement inhibition with the combination of sCR1 and HB-CPB limits damage during the revascularization of ischemic myocardium. Methods and Results-In 40 pigs, the second and third diagonal coronary arteries were occluded for 90 minutes, followed by 45 minutes of cardioplegic arrest and 180 minutes of reperfusion. In 10 pigs, sCR1 (10 mg/kg) was infused 5 minutes after the onset of coronary occlusion (sCR1), 10 received HB-CPB only (HB-CPB), 10 received sCR1 and HB-CPB (sCR1+HB), and 10 received neither sCR1 or HB-CPB (unmodified). Addition of sCR1 to the HB group resulted in less myocardial tissue acidosis (Delta pH = -0.72 +/- 0.03 for unmodified; -0.46 +/- 0.05* for HB; -0.18 +/- 0.04*dagger for sCR1; -0.13 +/- 0.01*dagger for sCR1+HB), better recovery of wall motion scores (4 = normal to -1 = dyskinesia; 1.67 +/- 0.17 for unmodified; 2.80 +/- 0.08* for HB; 3.35 +/- 0.10*dagger for sCR1; 3.59 +/- 0.08*dagger for sCR1 + HB), less lung water accumulation (5.46 +/- 0.28% for unmodified; 2.39 +/- 0.34% for HB; 1.22 +/- 0.07%*dagger for sCR1; 1.24 +/- 0.13%*dagger for sCR1+HB), and smaller infarct size (area necrosis/area risk = 44.6 +/- 0.7% for unmodified; 33.2 +/- 1.9%* for HB; 19.0 +/- 2.4%*dagger for sCR1; 20 +/- 1.0%*dagger for sCR1+HB) (*P<0.05 versus unmodified; dagger P<0.05 versus unmodified and HB groups). Conclusions-Total complement inhibition with sCR1 and sCR1+HB circuits optimizes recovery during the revascularization of ischemic myocardium.