Gallagher K P, Buda A J, Pace D, Gerren R A, Shlafer M
Circulation. 1986 May;73(5):1065-76. doi: 10.1161/01.cir.73.5.1065.
Superoxide dismutase (SOD) and catalase (CAT), enzymes that degrade superoxide anion and hydrogen peroxide, respectively, reduce size of infarction in anesthetized, open-chest dogs subjected to coronary occlusion followed by reperfusion. To evaluate potential protective effects of these enzymes in conscious animals, three groups of dogs were instrumented at sterile surgery with a hydraulic occluder on the left circumflex (LCX) coronary artery, sonomicrometers to measure regional wall thickness, and catheters to monitor arterial and left ventricular pressures. Ten to 14 days after surgery, the animals were sedated with morphine sulfate (0.5 mg/kg). The LCX artery was occluded for 3 hr by inflation of the hydraulic cuff. Infusions of SOD (n = 7), CAT (n = 6), or saline (control group, n = 7) were begun 15 min before reperfusion and lasted for 45 min of reperfusion. The doses of SOD and CAT were 5 mg/kg, dissolved in 60 ml of saline, and infused at a rate of 1 ml/min. Myocardial blood flow was measured with tracer-labeled microspheres (15 micron diameter) before occlusion, after 5 to 10 min of occlusion, after 150 min of occlusion, and 5 to 10 min after reperfusion. Size of infarction was measured 24 hr later by dual-perfusion staining with Evans blue and triphenyl tetrazolium. Size of infarction (expressed as a percentage of area at risk) did not differ significantly among the three groups: control, 32 +/- 17% (mean +/- SD); SOD, 38 +/- 17%; CAT, 27 +/- 17%. Hemodynamic parameters and myocardial blood flows (measured before infusion of any agents) were not significantly different among the three groups. Serum SOD levels in SOD-treated dogs were 19 +/- 2 micrograms/ml at the onset of reperfusion and 29 +/- 3 micrograms/ml at the end of the infusion. Blood assays collected after infusion showed a monoexponential decay of SOD levels with a half-life of 22 +/- 6 min. We conclude that myocardial protection by SOD or CAT is model dependent. In conscious dogs subjected to 3 hr of coronary occlusion followed by reperfusion, SOD and CAT failed to alter size of infarction.
超氧化物歧化酶（SOD）和过氧化氢酶（CAT）分别是降解超氧阴离子和过氧化氢的酶，它们可减小在冠状动脉闭塞后再灌注的麻醉开胸犬的梗死面积。为评估这些酶在清醒动物中的潜在保护作用，三组犬在无菌手术中通过液压闭塞器对左旋支（LCX）冠状动脉进行插管，用超声微测仪测量局部室壁厚度，并用导管监测动脉压和左心室压。术后10至14天，动物用硫酸吗啡（0.5mg/kg）镇静。通过液压袖带充气使LCX动脉闭塞3小时。在再灌注前15分钟开始输注SOD（n = 7）、CAT（n = 6）或生理盐水（对照组，n = 7），并持续再灌注45分钟。SOD和CAT的剂量为5mg/kg，溶解于60ml生理盐水中，以1ml/分钟的速率输注。在闭塞前、闭塞5至10分钟后、闭塞150分钟后以及再灌注5至10分钟后，用放射性标记的微球（直径15微米）测量心肌血流量。24小时后通过伊文思蓝和三苯基四氮唑双重灌注染色测量梗死面积。梗死面积（以危险区域面积的百分比表示）在三组之间无显著差异：对照组为32±17%（平均值±标准差）；SOD组为38±17%；CAT组为27±17%。三组之间的血流动力学参数和心肌血流量（在输注任何药物之前测量）无显著差异。在SOD治疗的犬中，再灌注开始时血清SOD水平为19±2μg/ml，输注结束时为29±3μg/ml。输注后采集的血液检测显示SOD水平呈单指数衰减，半衰期为22±6分钟。我们得出结论，SOD或CAT的心肌保护作用取决于模型。在经历3小时冠状动脉闭塞后再灌注的清醒犬中，SOD和CAT未能改变梗死面积。
