Nejima J, Knight D R, Fallon J T, Uemura N, Manders W T, Canfield D R, Cohen M V, Vatner S F
Department of Medicine, Harvard Medical School, Boston, Massachusetts.
Circulation. 1989 Jan;79(1):143-53. doi: 10.1161/01.cir.79.1.143.
To determine if oxygen free radical scavengers administered before coronary artery reperfusion can limit reperfusion arrhythmias, increase the return of regional function in ischemic myocardium, and reduce tissue necrosis at 1 week after 90-minute coronary artery occlusion and reperfusion, conscious dogs were treated with superoxide dismutase (SOD) and catalase before and for 1 hour after coronary artery reperfusion. Another group was treated with recombinant SOD (rSOD) because the commercially available SOD and catalase contained endotoxin. The conscious dogs were studied 3-4 weeks after implanting left ventricular pressure gauges, ultrasonic wall thickness gauges in the posterior left ventricular wall, left atrial catheters, and arterial catheters, Doppler flow transducers, and hydraulic occluders on the left circumflex coronary artery. The only beneficial effect observed was that the number of arrhythmic beats per minute in the rSOD-treated group was significantly lower (p less than 0.05) when compared with a control group after coronary artery reperfusion. Treatment neither increased the amount of recovery of wall thickening in the ischemic zone nor reduced infarct size when expressed either as a percentage of the area at risk or as a function of collateral blood flow in the ischemic zone. For example, infarct size as a percentage of the area at risk was 32.6 +/- 5.8%, 37.4 +/- 6.4%, 28.3 +/- 5.1% in the control, SOD and catalase-, and rSOD-treated groups, respectively. Thus, although treatment with oxygen free radical scavengers invoked a transient reduction in the number of reperfusion arrhythmias, this treatment in conscious dogs failed to improve regional myocardial dysfunction or reduce the amount of necrosis when compared with a control group. The lack of a sustained salutary effect may indicate that longer periods of treatment with free radical scavengers are required in chronic preparations.
为了确定在冠状动脉再灌注前给予氧自由基清除剂是否能限制再灌注心律失常、增加缺血心肌局部功能的恢复,并在冠状动脉闭塞90分钟及再灌注后1周减少组织坏死,对清醒犬在冠状动脉再灌注前及再灌注后1小时给予超氧化物歧化酶(SOD)和过氧化氢酶进行治疗。另一组用重组SOD(rSOD)治疗,因为市售的SOD和过氧化氢酶含有内毒素。在植入左心室压力计、左心室后壁超声壁厚计、左心房导管、动脉导管、多普勒血流传感器以及左旋支冠状动脉上的液压闭塞器3 - 4周后,对清醒犬进行研究。观察到的唯一有益效果是,与冠状动脉再灌注后的对照组相比,rSOD治疗组每分钟的心律失常次数显著降低(p小于0.05)。当以危险区域面积的百分比或缺血区域侧支血流的函数来表示时,治疗既未增加缺血区壁增厚的恢复量,也未减少梗死面积。例如,对照组、SOD和过氧化氢酶治疗组以及rSOD治疗组中,梗死面积占危险区域面积的百分比分别为32.6±5.8%、37.4±6.4%、28.3±5.1%。因此,尽管用氧自由基清除剂治疗可使再灌注心律失常的数量短暂减少,但与对照组相比,这种治疗在清醒犬中未能改善局部心肌功能障碍或减少坏死量。缺乏持续的有益效果可能表明在慢性制剂中需要更长时间的自由基清除剂治疗。