ANTIBODY TO CD-18 EXERTS ENDOTHELIAL AND CARDIAC PROTECTIVE EFFECTS IN MYOCARDIAL-ISCHEMIA AND REPERFUSION
ANTIBODY TO CD-18 EXERTS ENDOTHELIAL AND CARDIAC PROTECTIVE EFFECTS IN MYOCARDIAL-ISCHEMIA AND REPERFUSION
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DOI：
10.1172/jci115427
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发表时间：
1991-10-01
影响因子：
15.9
通讯作者：
LEFER, AM
中科院分区：
文献类型：
--
作者：
MA, XL;TSAO, PS;LEFER, AM
我们研究了MAbR15.7（一种针对中性粒细胞粘附糖蛋白家族共同β链（CD-18）的抗体）对猫心肌缺血再灌注模型内皮功能障碍和心肌损伤的影响。经戊巴比妥麻醉的猫进行1.5 h的左冠状动脉前降支闭塞和4.5 h的再灌注。MI + R导致严重的心肌损伤和内皮功能障碍，包括血浆肌酸激酶（CK）活性显著升高，心肌坏死明显，缺血心肌组织心肌髓过氧化物酶（MPO）活性升高，LAD冠状动脉环对内皮依赖性血管扩张剂乙酰胆碱（ACh）和A-23187的反应丧失。相比之下，mabr15.7治疗的猫在2小时后观察到的每个时间点的血浆CK活性都较低，心肌坏死面积减少（2 +/- 1比30.8 +/- 2.5%的危险面积，P < 0.001），缺血区域MPO活性降低（P < 0.01），并且LAD冠状动脉环对内皮依赖性血管扩张剂、ACh （P < 0.001）和a- 23187的血管松弛反应显著保留（P < 0.001）。这些结果表明，心肌缺血和再灌注在猫中引起明显的心肌损伤和内皮功能障碍，涉及cd18依赖性中性粒细胞粘附机制。抑制中性粒细胞粘附内皮在再灌注损伤模型中具有显著的保护作用。
We studied the effects of MAbR15.7, an antibody directed against the common beta-chain (CD-18) of a family of neutrophil adherence glycoproteins, on endothelial dysfunction and myocardial injury in a model of myocardial ischemia and reperfusion in cats. Pentobarbital-anesthetized cats were subjected to 1.5 h occlusion of the left anterior descending coronary artery (LAD) and 4.5 h of reperfusion. MI + R resulted in severe myocardial injury and endothelial dysfunction, including significant elevation of plasma creatine kinase (CK) activity, marked myocardial necrosis, high cardiac myeloperoxidase (MPO) activity in ischemic cardiac tissue, and loss of response of LAD coronary rings to the endothelium-dependent vasodilators, acetylcholine (ACh) and A-23187. In contrast, MAbR15.7-treated cats exhibited a lower plasma CK activity at every time point observed after 2 h, a reduced area of cardiac necrosis (2 +/- 1 vs. 30.8 +/- 2.5% of area-at-risk, P < 0.001), lower MPO activity in the ischemic region (P < 0.01), and significantly preserved vasorelaxant responses of LAD coronary rings to endothelium-dependent vasodilators, ACh (P < 0.001), and A-23187 (P < 0.001). These results indicate that myocardial ischemia and reperfusion induces significant myocardial injury and endothelial dysfunction in the cat involving a CD18-dependent neutrophil adherence mechanism. Inhibition of neutrophil adherence to the endothelium exerts significant protective effects in this model of reperfusion injury.