Black S C, Schasteen C S, Weiss R H, Riley D P, Driscoll E M, Lucchesi B R
Department of Pharmacology, University of Michigan Medical School, Ann Arbor.
J Pharmacol Exp Ther. 1994 Sep;270(3):1208-15.
We determined whether an organic superoxide dismutase mimetic could reduce myocardial injury resulting from a 90-min occlusion of the left circumflex coronary artery, followed by 18 hr of reperfusion in an anesthetized canine. The superoxide dismutase-mimetic studied (SC-52608) was a synthetic Mn-based macrocyclic compound. SC-52608 or the inactive analog SC-54385 was administered as four doses of 4 mg/kg i.v. Drug, inactive analog or vehicle was administered 30 and 15 min before ischemia and 15 min and immediately before reperfusion. To ensure parity of left circumflex coronary artery occlusion-induced ischemia, only animals with ischemic zone blood flow of less than 0.15 ml/min/g were included in the final analysis. Ischemic zone blood flow was 0.069 +/- 0.016 ml/min/g in control animals (n = 10), 0.072 +/- 0.010 ml/min/g in SC-52608-treated animals (n = 11) and 0.053 +/- 0.011 ml/min/g in SC-54385-treated (n = 9) animals. A transient hypotensive effect was observed upon SC-52608 administration. Hemodynamic parameters were otherwise unaffected by SC-52608 or SC-54385. The areas at risk of infarct were 39.6 +/- 1.9%, 38.7 +/- 1.1% and 39.4 +/- 1.1% in control, SC-52608-treated and SC-54385-treated animals, respectively. Myocardial infarct sizes (% of area at risk of infarct) were 44.2 +/- 5.6%, 25.7 +/- 4.3% and 35.1 +/- 4.9% in control, SC-52608-treated and SC-54385-treated animals, respectively (P < .05 control vs. SC-52608-treated). Therefore, the synthetic superoxide dismutase mimetic protected the regionally ischemic and reperfused myocardium from injury, implicating oxygen-derived radicals in the tissue-injury process.
我们研究了一种有机超氧化物歧化酶模拟物能否减轻在麻醉犬身上因左旋冠状动脉闭塞90分钟，随后再灌注18小时所导致的心肌损伤。所研究的超氧化物歧化酶模拟物（SC - 52608）是一种合成的锰基大环化合物。SC - 52608或无活性类似物SC - 54385以4毫克/千克静脉注射的方式分四次给药。药物、无活性类似物或赋形剂在缺血前30分钟和15分钟以及再灌注前15分钟和即将再灌注时给药。为确保左旋冠状动脉闭塞诱导的缺血情况一致，最终分析仅纳入缺血区血流小于0.15毫升/分钟/克的动物。对照组动物（n = 10）的缺血区血流为0.069±0.016毫升/分钟/克，接受SC - 52608治疗的动物（n = 11）为0.072±0.010毫升/分钟/克，接受SC - 54385治疗的动物（n = 9）为0.053±0.011毫升/分钟/克。给予SC - 52608后观察到短暂的降压作用。否则，血流动力学参数不受SC - 52608或SC - 54385影响。对照组、接受SC - 52608治疗组和接受SC - 54385治疗组动物的梗死危险区面积分别为39.6±1.9%、38.7±1.1%和39.4±1.1%。对照组、接受SC - 52608治疗组和接受SC - 54385治疗组动物的心肌梗死面积（占梗死危险区面积的百分比）分别为44.2±5.6%、25.7±4.3%和35.1±4.9%（对照组与接受SC - 52608治疗组相比，P < 0.05）。因此，这种合成的超氧化物歧化酶模拟物保护了局部缺血和再灌注的心肌免受损伤，提示氧衍生自由基参与了组织损伤过程。
