Uraizee A, Reimer K A, Murry C E, Jennings R B
Circulation. 1987 Jun;75(6):1237-48. doi: 10.1161/01.cir.75.6.1237.
Reactive oxygen species such as the superoxide anion (.O2-) have recently been implicated as important agents involved in causing cell death in the setting of myocardial ischemia and reperfusion. When superoxide anion is involved in ischemic injury the administration of superoxide dismutase (SOD) may limit infarct size by reducing the level of superoxide anions in the myocardium. The study described herein was done to determine whether SOD could limit myocardial infarct size when infarcts were produced in dogs by a 40 min occlusion of the circumflex coronary artery followed by 4 days of reperfusion. The animals in the SOD treatment group received a 1 hr intra-atrial infusion of SOD, at a rate of 250 U/kg/min starting 15 min after occlusion and ending 35 min after reperfusion; control dogs received a saline infusion over the same time frame. Infarct size was determined histologically and expressed as a percentage of the anatomic area at risk (AAR). Infarct size was similar in the two groups, averaging 26.2 +/- 2.5% in the control group (n = 10) and 21.1 +/- 4.8% in the SOD group (n = 11) (p = .40). Hemodynamic variables were not statistically different in the two groups during the occlusion. The transmural mean collateral blood flow at 10 min into the 40 min occlusion was 0.13 +/- 0.02 ml/min/g in the controls and 0.17 +/- 0.03 ml/min/g in the SOD group (p = NS); moreover, SOD did not alter collateral blood flow. In control dogs, infarct size was inversely related to collateral blood flow; analysis of covariance showed that SOD did not shift this relationship. Thus, SOD did not limit infarct size in this study. The results of the current study are consistent with our previous study in which allopurinol, a xanthine oxidase inhibitor, did not limit infarct size in this same experimental preparation. The results suggest that superoxide anions that are accessible to the infused SOD are not a major cause of myocyte death caused by 40 min of severe ischemia followed by reperfusion.
诸如超氧阴离子（·O₂⁻）等活性氧最近被认为是在心肌缺血和再灌注情况下导致细胞死亡的重要因素。当超氧阴离子参与缺血性损伤时，给予超氧化物歧化酶（SOD）可能通过降低心肌中超氧阴离子的水平来限制梗死面积。本文所述的研究旨在确定当通过闭塞左旋冠状动脉40分钟并随后再灌注4天在犬类中产生梗死时，SOD是否能够限制心肌梗死面积。SOD治疗组的动物在闭塞后15分钟开始，以250 U/kg/分钟的速率进行1小时的心房内SOD输注，再灌注后35分钟结束；对照犬在相同时间内接受生理盐水输注。通过组织学方法确定梗死面积，并表示为危险解剖区域（AAR）的百分比。两组的梗死面积相似，对照组（n = 10）平均为26.2±2.5%，SOD组（n = 11）平均为21.1±4.8%（p = 0.40）。在闭塞期间，两组的血流动力学变量无统计学差异。在40分钟闭塞开始10分钟时，对照组的透壁平均侧支血流为0.13±0.02 ml/分钟/克，SOD组为0.17±0.03 ml/分钟/克（p = 无显著性差异）；此外，SOD并未改变侧支血流。在对照犬中，梗死面积与侧支血流呈负相关；协方差分析表明SOD并未改变这种关系。因此，在本研究中SOD并未限制梗死面积。当前研究的结果与我们之前的研究一致，在之前的研究中，黄嘌呤氧化酶抑制剂别嘌呤醇在相同的实验制剂中并未限制梗死面积。结果表明，注入的SOD可接触到的超氧阴离子并非由40分钟严重缺血后再灌注导致的心肌细胞死亡的主要原因。
