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An antibody to leukocyte integrins attenuates coronary vascular injury due to ischemia and reperfusion in dogs
Journal article   Peer reviewed

An antibody to leukocyte integrins attenuates coronary vascular injury due to ischemia and reperfusion in dogs

Lawrence D Horwitz, Dimitri Kaufman and Yinong Kong
The American journal of physiology, Vol.272(2 Pt 2), pp.H618-H624
02/01/1997
DOI: 10.1152/ajpheart.1997.272.2.h618
PMID: 9124417

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Abstract

Ischemia and reperfusion cause coronary vascular and myocardial injury, which may be due to leukocyte-mediated processes. Antileukocyte measures have reduced injury after brief reperfusion periods of 1-3 h, but there has been little information on whether benefits are apparent after longer periods of reperfusion. We examined the effect of pretreatment with a monoclonal antibody (R15.7) to the CD18 family of leukocyte adhesion molecules (beta2-integrins) in dogs exposed to regional coronary ischemia for 1 h of left anterior descending coronary artery ligation and then reperfused for 48 h. Coronary microvascular permeability was assessed in vivo by measurement of protein leak index (PLI), using a double-isotope technique with autologous radiolabeled transferrin and erythrocytes. Vasorelaxation was measured in vitro with preconstricted epicardial coronary artery rings subjected to increasing concentrations of the endothelium-dependent vasodilators bradykinin (BK) and ADP and the endothelium-independent vasodilator nitroprusside. At 48 h of reperfusion in untreated dogs there were substantial increases in PLI in the previously ischemic regions, indicative of increased extravascular transferrin. These abnormalities were decreased, but not abolished, in the dogs treated with R15.7. Relaxation of rings from the ischemic/reperfused artery to BK and ADP were blunted in the untreated dogs. R15.7 resulted in improvement in some, but not all, indexes of relaxation in response to BK and ADP. Relaxation to nitroprusside was normal in ischemic/reperfused coronary rings from both treated and untreated dogs. Therefore, after 1 h of regional coronary ischemia and 48 h of reperfusion, coronary endothelial injury, which was manifested by increased coronary microvascular permeability and abnormalities in coronary endothelium-dependent relaxation, was reduced by pretreatment with the anti-CD18 integrin antibody R15.7.
Animals Antibodies - immunology Antibodies - pharmacology Blood Proteins - metabolism Capillary Permeability Coronary Vessels - drug effects Coronary Vessels - pathology Coronary Vessels - physiopathology Dogs In Vitro Techniques Integrins - immunology Leukocytes - metabolism Male Myocardial Ischemia - pathology Myocardial Ischemia - physiopathology Myocardial Reperfusion Injury - pathology Myocardial Reperfusion Injury - physiopathology Neutrophils - immunology Pericardium - physiopathology Vasodilation

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