Werns S W, Simpson P J, Mickelson J K, Shea M J, Pitt B, Lucchesi B R
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor 48109.
J Cardiovasc Pharmacol. 1988 Jan;11(1):36-44. doi: 10.1097/00005344-198801000-00006.
This study was performed to evaluate the effects of superoxide dismutase, a scavenger of superoxide anions, on leukocyte accumulation and myocardial injury in a canine preparation of myocardial infarction. Dogs underwent occlusion of the left circumflex coronary artery for 90 min, followed by a reperfusion for 6 or 24 h. The dogs received either saline or superoxide dismutase (5 mg/kg), beginning 15 min before coronary occlusion and ending 15 min after coronary reflow. Myocardial infarct size, expressed as a percentage of the area at risk, was significantly less in superoxide-dismutase-treated dogs that underwent reperfusion for 6 h, 17.5 +/- 1.7, or 24 h, 25.8 +/- 3.6, compared to saline-treated dogs that underwent reperfusion for 6 h, 42.7 +/- 4.4 (p less than 0.05), or 24 h, 53.0 +/- 6.1 (p less than 0.05). The differences in infarct size were not due to differences in myocardial oxygen demand. Superoxide dismutase had no effect on regional myocardial perfusion of the ischemic bed. Accumulation of 111indium (In)-labeled autologous leukocytes within the area at risk was similar in control and superoxide-dismutase-treated dogs (p greater than 0.05). The results suggest that oxygen radicals play a role in the extent of injury due to regional myocardial ischemia followed by reperfusion, and the protective effect of free radical scavengers may be sustained beyond the expected plasma half-life of the administered agent.
本研究旨在评估超氧化物阴离子清除剂超氧化物歧化酶对犬心肌梗死模型中白细胞聚集和心肌损伤的影响。犬左回旋支冠状动脉闭塞90分钟，随后再灌注6或24小时。犬在冠状动脉闭塞前15分钟开始，冠状动脉再灌注后15分钟结束，接受生理盐水或超氧化物歧化酶（5mg/kg）治疗。与接受6小时再灌注的生理盐水治疗犬（42.7±4.4，p<0.05）或24小时再灌注的生理盐水治疗犬（53.0±6.1，p<0.05）相比，接受6小时再灌注（17.5±1.7）或24小时再灌注（25.8±3.6）的超氧化物歧化酶治疗犬，以危险区域面积百分比表示的心肌梗死面积显著减小。梗死面积的差异并非由于心肌需氧量的差异。超氧化物歧化酶对缺血床的局部心肌灌注无影响。在对照组和超氧化物歧化酶治疗犬的危险区域内，111铟（In）标记的自体白细胞聚集情况相似（p>0.05）。结果表明，氧自由基在局部心肌缺血再灌注所致损伤程度中起作用，自由基清除剂的保护作用可能在给药药物预期的血浆半衰期之后仍持续存在。
