Protective effects of N-2-mercaptopropionyl glycine against myocardial reperfusion injury after neutrophil depletion in the dog: evidence for the role of intracellular-derived free radicals.
Protective effects of N-2-mercaptopropionyl glycine against myocardial reperfusion injury after neutrophil depletion in the dog: evidence for the role of intracellular-derived free radicals.
复制标题
N-2-巯基丙酰甘氨酸对狗中性粒细胞耗竭后心肌再灌注损伤的保护作用：细胞内衍生自由基作用的证据。
作者：
S. E. Mitsos;Timothy Askew;J. Fantone;S. Kunkel;G. Abrams;A. Schork;B. Lucchesi
缺血心肌的再灌注与氧自由基及其代谢产物的产生有关，氧自由基及其代谢产物导致不可逆心肌损伤的最终程度。多形核白细胞与细胞内衍生的氧代谢产物的相对重要性仍然不确定。我们评估了自由基清除剂N-2-巯基丙酰甘氨酸（MPG）在限制犬缺血/再灌注后梗死面积方面的有效性，这些犬用特异性抗血清耗尽了中性粒细胞。24只麻醉开胸犬，结扎左冠状动脉回旋支，缺血90分钟，再灌注6小时。将狗随机分配到接受非免疫血清、中性粒细胞抗血清或中性粒细胞抗血清加MPG（20 mg/kg，在再灌注开始前15 min和再灌注后45 min心房内注射）。与非免疫组相比，中性粒细胞抗血清组的肿瘤大小（占危险区域的百分比）减少了33%（30.7 ± 2.7% vs 45.6 ± 3.7%，p <0.01）。与非免疫组相比，联合应用中性粒细胞抗血清和MPG可使梗死面积减少63%（17.0 ± 2.7% vs 45.6 ± 3.7%，p <0.01）。中性粒细胞抗血清加MPG对梗死面积的减少明显大于单独使用中性粒细胞抗血清（p <0.01）。各组之间的风险领域没有差异。不能根据血流动力学差异解释心肌保护。MPG增强中性粒细胞耗竭的保护作用的观察结果表明，心肌外和心肌内衍生的氧自由基都对再灌注诱导的心肌损伤有显着贡献。
Reperfusion of the previously ischemic myocardium is associated with the production of oxygen free radicals and their metabolites, which contribute to the ultimate extent of irreversible myocardial injury. The relative importance of polymorphonuclear leukocytes vs intracellular-derived oxygen metabolites has remained uncertain. We evaluated the effectiveness of a free-radical scavenger, N-2-mercaptopropionyl glycine (MPG), in limiting infarct size after ischemia/reperfusion in dogs that were depleted of neutrophils with specific antisera. Twenty-four urethane-anesthetized open-chest dogs were subjected to 90 min of ischemia by occlusion of the left circumflex coronary artery followed by 6 hr of reperfusion. Dogs were randomly assigned to receive nonimmune serum, neutrophil antiserum, or neutrophil antiserum plus MPG (20 mg/kg intra-atrially 15 min before reperfusion was initiated and for 45 min after reperfusion). Infarct size, as a percent of the area at risk, was reduced by 33% in the neutrophil antiserum group as compared with the nonimmune group (30.7 +/- 2.7% vs 45.6 +/- 3.7%, p less than .01). The combined administration of neutrophil antiserum plus MPG reduced the size of infarction by 63% of the area at risk compared with that in the nonimmune group (17.0 +/- 2.7% vs 45.6 +/- 3.7%, p less than .01). The reduction in infarct size with neutrophil antiserum plus MPG was significantly greater than that with the neutrophil antiserum alone (p less than .01). The areas at risk did not differ among the groups. Myocardial protection could not be explained on the basis of hemodynamic differences. The observation that MPG enhances the protective effects of neutrophil depletion suggests that both extramyocardial- and intramyocardial-derived oxygen free radicals contribute significantly to reperfusion-induced myocardial injury.
登录
查看更多内容
DOI：
--
发表时间：
1983-04
期刊：
The American journal of pathology
影响因子：
--
作者：
R. Engler;G. Schmid-Schönbein;R. Pavelec
通讯作者：
R. Engler;G. Schmid-Schönbein;R. Pavelec
巯基化合物调节肌红蛋白-H2O2 介导的过氧化反应。
DOI：
--
发表时间：
1988
期刊：
Laboratory investigation; a journal of technical methods and pathology
影响因子：
--
作者：
Mitsos,SE;Kim,D;Lucchesi,BR;Fantone,JC
通讯作者：
Fantone,JC
黄嘌呤氧化酶抑制剂别嘌呤醇未能限制狗缺血和再灌注后的梗塞面积。
影响因子：
37.8
作者：
Reimer,KA;Jennings,RB
通讯作者：
Jennings,RB
努力限制心肌梗塞的范围。
影响因子：
39.2
作者：
Rude,RE;Muller,JE;Braunwald,E
通讯作者：
Braunwald,E