(Circulation. 1999;100:1438-1442.)
© 1999 American Heart Association, Inc.
Basic Science Reports |
Total Complement Inhibition
An Effective Strategy to Limit Ischemic Injury During Coronary Revascularization on Cardiopulmonary Bypass
From the Department of Cardiothoracic Surgery, Boston University School of Medicine and Boston Medical Center, Boston, Mass.
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 (
pH=-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.
Key Words: heparin • myocardial infarction
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