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.


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 (DeltapH = -0.72+/-0.03 for unmodified; -0.46+/-0.05 for HB; -0.18+/-0.04 for sCR1; -0.13+/-0.01 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 for sCR1; 3.59+/-0.08 for sCR1+HB), less lung water accumulation (5.46+/-0.28% for unmodified; 2.39+/-0.34% for HB; 1.22+/-0.07% for sCR1; 1.24+/-0.13% 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% for sCR1; 20+/-1.0% for sCR1+HB) (P<0.05 versus unmodified; 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.
Lazar
H L
HL
Department of Cardiothoracic Surgery, Boston University School of Medicine and Boston Medical Center, Boston, Mass 02118, USA.
Bao
Y
Y
Gaudiani
J
J
Rivers
S
S
Marsh
H
H
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001834:Body Water / Q000378:metabolism; D002315:Cardiopulmonary Bypass; D003169:Complement Inactivator Proteins / Q000494:pharmacology*; D003165:Complement System Proteins / Q000032:analysis; D006321:Heart / Q000503:physiopathology; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008168:Lung / Q000378:metabolism; D009203:Myocardial Infarction / Q000473:pathology; D017202:Myocardial Ischemia / Q000097:blood / Q000473:pathology* / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000473:pathology* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D011951:Receptors, Complement / Q000502:physiology*; D012995:Solubility; D013552:Swine
D000925:Anticoagulants; D003169:Complement Inactivator Proteins; D011951:Receptors, Complement; D006493:Heparin; D003165:Complement System Proteins