Circulation, Vol 86, 937-946, Copyright © 1992 by American Heart Association
XL Ma, DJ Lefer, AM Lefer and R Rothlein
BACKGROUND. Intercellular adhesion molecule-1 (ICAM-1) is a major ligand on
endothelial cells for adherence of activated polymorphonuclear leukocytes
(PMNs). The major purpose of this study was to study the effects of RR1/1,
a monoclonal antibody against ICAM-1 (i.e., MAb RR1/1), on myocardial
injury and endothelial dysfunction associated with myocardial ischemia and
reperfusion. METHODS AND RESULTS. Either MAb RR1/1 (2 mg/kg, n = 7), an
antibody that was found to bind selectively to endothelial cells in the
cat, or MAb R3.1 (2 mg/kg, n = 7), a nonbinding control antibody, was given
as an intravenous bolus 10 minutes before reperfusion. Two hundred eighty
minutes later, hearts were excised. The left ventricle area-at-risk (AAR)
was similar in MAb RR1/1 (29 +/- 2%) and MAb R3.1 (30 +/- 3%) groups. In
MAb R3.1-treated cats, 90 minutes of myocardial ischemia plus 4.5 hours of
reperfusion induced a significant myocardial injury (necrotic tissue/AAR,
28 +/- 2%), high myeloperoxidase activity (0.65 +/- 0.16 units/100 mg
ischemic tissue), and a marked decrease in endothelium-dependent
vasorelaxation in isolated left anterior descending coronary arteries
(vasorelaxation to acetylcholine, 29 +/- 3%) with no change in
endothelium-independent vasorelaxation (relaxation to NaNO2, 91 +/- 3%).
However, cats treated with MAb RR1/1 developed significantly less
myocardial necrosis (10 +/- 2% of the AAR, p less than 0.01), lower
myeloperoxidase activity in ischemic myocardial tissue (0.2 +/- 0.03
units/100 mg ischemic tissue, p less than 0.01), and enhanced vasorelaxant
responses to endothelial- dependent relaxation to acetylcholine (53 +/- 5%)
compared with ischemic/reperfused cats treated with Mab R3.1. Furthermore,
addition of MAb RR1/1 in vitro significantly inhibited unstimulated PMN
adherence to ischemic-reperfused coronary artery endothelium. CONCLUSIONS.
These results suggest that ICAM-1-dependent PMN adherence plays an
important role in reperfusion injury, and that PMN adherence and
infiltration contribute significantly to coronary endothelial dysfunction.
ARTICLES
Coronary endothelial and cardiac protective effects of a monoclonal antibody to intercellular adhesion molecule-1 in myocardial ischemia and reperfusion
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107.
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F. E. Schmidt Jr, M. J. MacDonald, C. O. Murphy, W. M. Brown III, J. P. Gott, and R. A. Guyton Leukocyte Depletion of Blood Cardioplegia Attenuates Reperfusion Injury Ann. Thorac. Surg., December 1, 1996; 62(6): 1691 - 1696. [Abstract] [Full Text]
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E. M. Boyle Jr, T. H. Pohlman, C. J. Cornejo, and E. D. Verrier Endothelial Cell Injury in Cardiovascular Surgery: Ischemia-Reperfusion Ann. Thorac. Surg., December 1, 1996; 62(6): 1868 - 1875. [Abstract] [Full Text]
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T. Miura, D. P. Nelson, M. L. Schermerhorn, T. Shin'oka, G. Zund, P. R. Hickey, E. J. Neufeld, and J. E. Mayer Jr Blockade of Selectin-Mediated Leukocyte Adhesion Improves Postischemic Function in Lamb Hearts Ann. Thorac. Surg., November 1, 1996; 62(5): 1295 - 1300. [Abstract] [Full Text]
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F. M. Sheridan, P. G. Cole, and D. Ramage Leukocyte Adhesion to the Coronary Microvasculature During Ischemia and Reperfusion in an In Vivo Canine Model Circulation, May 15, 1996; 93(10): 1784 - 1787. [Abstract] [Full Text]
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J. M. Forbess, T. Hiramatsu, F. Nomura, T. Miura, G. K. Farrington, K. Sokolowski, M. Bree, and J. E. Mayer Jr Anti-CD11b Monoclonal Antibody Improves Myocardial Function After Six Hours of Hypothermic Storage Ann. Thorac. Surg., November 1, 1995; 60(5): 1238 - 1244. [Abstract] [Full Text]
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M. C. Oz, H. Liao, Y. Naka, A. Seldomridge, D. N. Becker, R. E. Michler, C. R. Smith, E. A. Rose, D. M. Stern, and D. J. Pinsky Ischemia-Induced Interleukin-8 Release After Human Heart Transplantation : A Potential Role for Endothelial Cells Circulation, November 1, 1995; 92(9): 428 - 432. [Abstract] [Full Text]
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K. Kaikita, H. Ogawa, H. Yasue, T. Sakamoto, H. Suefuji, H. Sumida, and K. Okumura Soluble P-Selectin Is Released Into the Coronary Circulation After Coronary Spasm Circulation, October 1, 1995; 92(7): 1726 - 1730. [Abstract] [Full Text]
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F.-J. Neumann, I. Ott, M. Gawaz, G. Richardt, H. Holzapfel, M. Jochum, and A. Schomig Cardiac Release of Cytokines and Inflammatory Responses in Acute Myocardial Infarction Circulation, August 15, 1995; 92(4): 748 - 755. [Abstract] [Full Text]
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G. L. Stahl, W. R. Reenstra, and G. Frendl Complement-Mediated Loss of Endothelium-Dependent Relaxation of Porcine Coronary Arteries : Role of the Terminal Membrane Attack Complex Circ. Res., April 1, 1995; 76(4): 575 - 583. [Abstract] [Full Text]
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P. R. Hansen Role of Neutrophils in Myocardial Ischemia and Reperfusion Circulation, March 15, 1995; 91(6): 1872 - 1885. [Abstract] [Full Text]
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M. Buerke, T. Murohara, and A. M. Lefer Cardioprotective Effects of a C1 Esterase Inhibitor in Myocardial Ischemia and Reperfusion Circulation, January 15, 1995; 91(2): 393 - 402. [Abstract] [Full Text]
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P. M. Kilbridge, J. E. Mayer, J. W. Newburger, P. R. Hickey, A. Z. Walsh, and E. J. Neufeld Induction of intercellular adhesion molecule-1 and E-selectin mRNA in heart and skeletal muscle of pediatric patients undergoing cardiopulmonary bypass J. Thorac. Cardiovasc. Surg., May 1, 1994; 107(5): 1183 - 1192. [Abstract] [Full Text]
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 D. A Palanzo, N. J Manley, R. M Montesano, G. L Yeisley, and D. Gordon Clinical evaluation of the LeukoGuard (LG-6) arterial line filter for routine open-heart surgery Perfusion, November 1, 1993; 8(6): 489 - 496. [Abstract] [PDF]
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R. A. Bowden, Z.-M. Ding, E. M. Donnachie, T. K. Petersen, L. H. Michael, C. M. Ballantyne, and A. R. Burns Role of {alpha}4 Integrin and VCAM-1 in CD18-Independent Neutrophil Migration Across Mouse Cardiac Endothelium Circ. Res., March 22, 2002; 90(5): 562 - 569. [Abstract] [Full Text] [PDF]
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