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Biotech / Medical : Gliatech (GLIA)

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To: Dr. John M. de Castro who wrote (1476)3/9/2000 10:51:00 PM
From: Dr. John M. de Castro   of 2001
 
Still more on complement inhibition for bypass

Total complement inhibition: an effective strategy to limit ischemic injury during coronary revascularization on cardiopulmonary bypass.
Circulation 1999 Sep 28;100(13):1438-42
Lazar HL, Bao Y, Gaudiani J, Rivers S, Marsh H
Department of Cardiothoracic Surgery, Boston University School of Medicine and Boston Medical Center,
Boston, Mass 02118, USA.

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 (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.
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