This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lazar, H. L. Articles by Marsh, H. Search for Related Content PubMed PubMed Citation Articles by Lazar, H. L. Articles by Marsh, H. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Cardiomyopathy Hazardous Substances DB HEPARIN Related Collections Animal models of human disease Ischemic biology - basic studies Anticoagulant mechanisms

(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

Harold L. Lazar, MD; Yusheng Bao, MD; Jennifer Gaudiani, BA; Samuel Rivers, BS; Henry Marsh, PhD

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

This article has been cited by other articles:

				Y. Banz, O. M. Hess, S. C. Robson, E. Csizmadia, D. Mettler, P. Meier, A. Haeberli, S. Shaw, R. A. Smith, and R. Rieben Attenuation of myocardial reperfusion injury in pigs by Mirococept, a membrane-targeted complement inhibitor derived from human CR1 Cardiovasc Res, December 1, 2007; 76(3): 482 - 493. [Abstract] [Full Text] [PDF]

				L. J. Thomas, K. Panneerselvam, D. T. Beattie, M. D. Picard, B. Xu, C. W. Rittershaus, H. C. Marsh Jr., R. A. Hammond, J. Qian, T. Stevenson, et al. Production of a complement inhibitor possessing sialyl Lewis X moieties by in vitro glycosylation technology Glycobiology, October 1, 2004; 14(10): 883 - 893. [Abstract] [Full Text] [PDF]

				H. L. Lazar, P. M. Bokesch, F. van Lenta, C. Fitzgerald, C. Emmett, H. C. Marsh Jr, U. Ryan, and OBE and the TP10 Cardiac Surgery Study Group Soluble Human Complement Receptor 1 Limits Ischemic Damage in Cardiac Surgery Patients at High Risk Requiring Cardiopulmonary Bypass Circulation, September 14, 2004; 110(11_suppl_1): II-274 - II-279. [Abstract] [Full Text] [PDF]

				K. T. Lappegard, M. Fung, G. Bergseth, J. Riesenfeld, J. D. Lambris, V. Videm, and T. E. Mollnes Effect of complement inhibition and heparin coating on artificial surface-induced leukocyte and platelet activation Ann. Thorac. Surg., March 1, 2004; 77(3): 932 - 941. [Abstract] [Full Text] [PDF]

				A. J. Chong, C. R. Hampton, and E. D. Verrier Microvascular Inflammatory Response in Cardiac Surgery Seminars in Cardiothoracic and Vascular Anesthesia, September 1, 2003; 7(3): 333 - 354. [Abstract] [PDF]

				I. Risnes, T. Ueland, R. Lundblad, T. E. Mollnes, S. T. Baksaas, P. Aukrust, and J. L. Svennevig Changes in the cytokine network and complement parameters during open heart surgery Interactive CardioVascular and Thoracic Surgery, March 1, 2003; 2(1): 19 - 24. [Abstract] [Full Text] [PDF]

				H. I Flom-Halvorsen, E Ovrum, F Brosstad, G Tangen, M A. Ringdal, and R Oystese Effects of two differently heparin-coated extracorporeal circuits on markers for brain and myocardial dysfunction Perfusion, September 1, 2002; 17(5): 339 - 345. [Abstract] [PDF]

				H. L. Lazar, Y. Bao, S. Rivers, and S. A. Bernard Pretreatment with angiotensin-converting enzyme inhibitors attenuates ischemia-reperfusion injury Ann. Thorac. Surg., May 1, 2002; 73(5): 1522 - 1527. [Abstract] [Full Text] [PDF]

				L.-C. Hsu Heparin-coated cardiopulmonary bypass circuits: current status Perfusion, September 1, 2001; 16(5): 417 - 428. [Abstract] [PDF]

				C.H. Davies Revascularization for cardiogenic shock QJM, February 1, 2001; 94(2): 57 - 67. [Full Text] [PDF]