A CHIMERIC IGG4 MONOCLONAL-ANTIBODY DIRECTED AGAINST CD18 REDUCES INFARCT SIZE IN A PRIMATE MODEL OF MYOCARDIAL-ISCHEMIA AND REPERFUSION
A CHIMERIC IGG4 MONOCLONAL-ANTIBODY DIRECTED AGAINST CD18 REDUCES INFARCT SIZE IN A PRIMATE MODEL OF MYOCARDIAL-ISCHEMIA AND REPERFUSION
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DOI：
10.1016/0735-1097(94)00443-t
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发表时间：
1995-03-01
影响因子：
24
通讯作者：
WEISMAN, H
中科院分区：
文献类型：
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作者：
AVERSANO, T;ZHOU, W;WEISMAN, H
目标.本研究试图确定在急性心肌缺血和再灌注的灵长类动物模型中，是否可以通过针对CD 18的嵌合单克隆IgG 4抗体（CLB 54）治疗来抑制再灌注心肌中的中性粒细胞隔离并减少梗死面积。中性粒细胞介导的再灌注损伤可能限制急性心肌梗死患者梗死相关动脉再通的潜在益处。19只闭胸狒狒（10只对照，9只CLB 54治疗）左前降支冠状动脉闭塞90分钟，然后再流4小时。在复流前20分钟静脉内给予CLB 54（平均值[+/-SD] 11 +/- 2 mg/kg体重）或盐水溶液。冠状动脉血流测定采用放射性标记微球，梗死面积测定采用氯化三苯基四氮唑染色法，整体和局部心室功能测定采用对比心室造影法，中性粒细胞聚集测定采用髓过氧化物酶法。两组的风险区域大小相同。CLB 54治疗将梗死面积从生理盐水治疗组的41 +/-20%降低至CLB 54治疗组的19 +/-17%（p < 0.02），梗死面积表示为风险区域的百分比。这与髓过氧化物酶活性降低和CLB 54治疗的风险区域中的再灌注后冠状动脉流量大于对照狒狒相关。两组射血分数下降的程度相同，而CLB 54治疗的狒狒更好地保留了前壁区域脊髓缩短。在再灌注前给予CLB 54抑制中性粒细胞隔离可减小梗死面积，保持缺血区微血管灌注，并使局部室壁运动的下降最小化。
Objectives. This study attempted to determine whether neutrophil sequestration in reperfused myocardium can be inhibited and infarct size reduced by treatment with a chimeric, monoclonal IgG4 antibody (CLB54) directed against CD18 in a primate model of acute myocardial ischemia and reperfusion.Background. Reperfusion injury, in part mediated by neutrophils, may limit the potential benefit of reestablishing infarct-related artery patency in patients with acute myocardial infarction.Methods. Nineteen closed-chest baboons (10 control, 9 treated with CLB54) had the left anterior descending coronary artery occluded for 90 min, followed by 4 h of reflow. CLB54 (mean [+/-SD] 11 +/- 2 mg/kg body weight) or saline solution was administered intravenously 20 min before reflow. Coronary flow was determined using radiolabeled microspheres, infarct size by triphenyltetrazolium chloride staining, global and regional ventricular function by contrast ventriculography and neutrophil accumulation by a myeloperoxidase assay.Results. Risk region size was the same in both groups. CLB54 treatment reduced infarct size expressed as a percent of the risk region from 41 +/- 20% in the saline-treated group to 19 +/- 17% in the CLB54-treated group (p < 0.02). This was associated with diminished myeloperoxidase activity and greater postreperfusion coronary flow in the risk region in CLB54-treated than in control baboons. Ejection fraction declined to the same extent in both groups, whereas anterior wall regional cord shortening was better preserved in CLB54-treated baboons.Conclusions. Inhibition of neutrophil sequestration with CLB54 administered before reperfusion reduces infarct size, preserves ischemic zone microvascular perfusion and minimizes the decline of regional wall motion.