Ma X L, Johnson G, Lefer A M
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylavania 19107-6799.
J Am Coll Cardiol. 1992 Jan;19(1):197-204. doi: 10.1016/0735-1097(92)90073-v.
The effects of low dose human superoxide dismutase and low dose taprostene, a stable analogue of prostacyclin, were investigated separately and together in a model of myocardial ischemia (1.5 h) with reperfusion (4.5 h) in open chest, anesthetized cats. Taprostene (60 ng/kg per min), human superoxide dismutase (0.25 mg/kg per h), both agents together, or their vehicle, were infused intravenously in cats starting 0.5 h after occlusion of the left anterior descending coronary artery. Neither low dose taprostene nor low dose human superoxide dismutase exerted any endothelial or myocardial protection in this model. However, the two agents together showed a significant endothelial and myocardial protection in cats with myocardial ischemia and reperfusion. Compared with cats that were untreated or received only taprostene or human superoxide dismutase, cats receiving both agents exhibited a lower plasma creatine kinase activity at every time point observed after reperfusion, a reduced area of cardiac necrosis (7 +/- 2% vs. 21 +/- 5% area at risk, p less than 0.001), lower myeloperoxidase activity in the ischemic region (p less than 0.01) and a significant preservation of vasorelaxant responses of left anterior descending coronary rings to endothelium-dependent vasodilators, acetylcholine (p less than 0.001) and A-23187 (p less than 0.001). Taprostene appears to act additively with human superoxide dismutase to inhibit neutrophil adherence and activation and to inactivate superoxide radicals, and thus reduce cellular injury 4.5 h after reperfusion of the ischemic heart. Use of this agent may allow low doses of superoxide dismutase to be used more effectively in early myocardial ischemia.
在开胸、麻醉的猫的心肌缺血（1.5小时）再灌注（4.5小时）模型中，分别单独研究了低剂量人超氧化物歧化酶和低剂量曲前列环素（前列环素的一种稳定类似物）的作用，以及它们联合使用的效果。在左冠状动脉前降支闭塞0.5小时后，给猫静脉输注曲前列环素（每分钟60纳克/千克）、人超氧化物歧化酶（每小时0.25毫克/千克）、两种药物联合使用或它们的赋形剂。在该模型中，低剂量曲前列环素和低剂量人超氧化物歧化酶均未发挥任何内皮或心肌保护作用。然而，两种药物联合使用对心肌缺血再灌注的猫显示出显著的内皮和心肌保护作用。与未治疗或仅接受曲前列环素或人超氧化物歧化酶的猫相比，接受两种药物的猫在再灌注后观察的每个时间点血浆肌酸激酶活性均较低，心脏坏死面积减小（危险面积的7±2%对21±5%，p<0.001），缺血区域髓过氧化物酶活性较低（p<0.01），并且左冠状动脉前降支环对内皮依赖性血管舒张剂乙酰胆碱（p<0.001）和A-23187（p<0.001）的血管舒张反应得到显著保留。曲前列环素似乎与人超氧化物歧化酶协同作用，抑制中性粒细胞黏附和活化，并使超氧阴离子失活，从而减少缺血心脏再灌注4.5小时后的细胞损伤。使用该药物可能使低剂量超氧化物歧化酶在早期心肌缺血中更有效地发挥作用。
