COMPLEMENT AND NEUTROPHIL ACTIVATION IN THE PATHOGENESIS OF ISCHEMIC MYOCARDIAL INJURY
COMPLEMENT AND NEUTROPHIL ACTIVATION IN THE PATHOGENESIS OF ISCHEMIC MYOCARDIAL INJURY
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DOI：
10.1161/01.cir.78.6.1449
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发表时间：
1988-12-01
期刊：
影响因子：
37.8
通讯作者：
PINCKARD, RN
中科院分区：
文献类型：
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作者：
CRAWFORD, MH;GROVER, FL;PINCKARD, RN
冠状动脉结扎前用眼镜蛇毒因子（CVF）进行补体耗竭已被证明可减少狒狒随后的缺血性心肌组织损伤;然而，急性心肌缺血后补体耗竭是否能提供类似的心肌保护尚不清楚。CVF的补体耗竭或某些非甾体抗炎药（包括布洛芬）的给药均被认为可通过减少多形核白细胞（PMN）浸润来减少心肌梗死面积;然而，补体激活也可通过PMN非依赖性作用改变组织损伤。因此，在狒狒心肌梗死模型中评估了冠状动脉结扎后给予CVF对随后心肌组织损伤发展的相对影响。将动物随机分为三个治疗组（n = 6）：冠状动脉结扎后30分钟给予CVF（125单位/kg）或盐水，结扎后30分钟和4小时给予布洛芬（12.5mg.kg）。24小时后评估缺血性心肌损伤的程度。相对于盐水处理的狒狒，CVF和布洛芬都减少了PMN浸润（36 . ±. 4与24 .+-. 4和24 .+-。分别为4个PMN/mm 2;平均值±。扫描电镜）和组织学证据（分别为100%与47%和53%）的透壁心肌梗死，在心电图指定的，预期的梗死部位。在生理盐水和布洛芬治疗的动物中，在所有梗死部位均存在广泛的C4、C3和C5定位;相反，CVF治疗的狒狒中仅存在C4定位。当评估预期梗塞部位的肌酸激酶含量作为组织损伤的指标时，在CVF处理的动物中，心外膜和心内膜肌酸激酶消耗显著较少（31.7 ± 0.01）。5.6%和39.3 ±。4.8%）比盐水处理的动物（54.1 . ±. 5.4%和59.0 ±。4.7%; p分别为0.012和0.011）。布洛芬给药动物的肌酸激酶消耗百分比介于其他两组之间。这些结果表明，冠状动脉结扎后的补体耗竭在减少组织损伤方面具有有益作用，这不能仅仅根据减少PMN浸润到缺血心肌中来解释。
Complement depletion with cobra venom factor (CVF) before coronary artery ligation had been previously shown to reduce subsequent ischemic myocardial tissue injury in the baboon; however, whether complement depletion after the initiation of acute myocardial ischemia affords similar myocardial preservation is not known. Both complement depletion with CVF or the administration of certain nonsteroidal anti-inflammatory drugs, including ibuprofen, are thought to decrease myocardial infarct size by reducing polymorphonuclear leukocytic (PMN) infiltration; nevertheless, complement activation also could alter tissue injury by PMN-independent actions. Thus, the relative effects of CVF administered after coronary artery ligation on the subsequent development of myocardial tissue injury were assessed in a baboon myocardial infarction model. The animals were randomized into three treatment groups (n = 6): either CVF (125 units/kg) or saline was given 30 minutes after coronary artery ligation, and ibuprofen (12.5 mg.kg) was administered 30 minutes and 4 hours after ligation. The extent of ischemic myocardial injury was assessed 24 hours later. Relative to saline-treated baboons, both CVF and ibuprofen reduced PMN infiltration (36 .+-. 4 vs. 24 .+-. 4 and 24 .+-. 4 PMN/mm2, respectively; mean .+-. SEM) and histological evidence of transmural myocardial infarction (100% vs. 47% and 53%, respectively) in electrocardiographically designated, expected infarct sites. In both saline- and ibuprofen-treated animals, there was extensive localization of C4, C3, and C5 in all infarct sites; in contrast, there was only C4 localization in the CVF-treated baboons. When expected infarct sites were assessed for creatine kinase content as an indicator of tissue injury, there was significantly less epicardial and endocardial creatine kinase depletion in the CVF-treated animals (31.7 .+-. 5.6% and 39.3 .+-. 4.8%) than in the saline-treated animals (54.1 .+-. 5.4% and 59.0 .+-. 4.7%; p = 0.012 and 0.011, respectively). The percent creatine kinase depletion in the ibuprofen-treated animals was intermediate between the two other groups. These results suggest that depletion of complement after coronary ligation has beneficial effects in reducing tissue injury that cannot be explained solely on the basis of reducing PMN infiltration into the ischemic myocardium.