Pisarenko O I, Studneva I M, Lakomkin V L, Timoshin A A, Kapelko V I
Institute of Experimental Cardiology, Academy of Medical Sciences, Moscow, Russia.
J Cardiovasc Pharmacol. 1994 Oct;24(4):655-63. doi: 10.1097/00005344-199410000-00017.
The cardioprotective effects of human recombinant extracellular-superoxide dismutase type C (hr-EC-SOD C) were compared with those of bovine Cu,Zn-SOD in isolated working rat heart subjected to 35-min global normothermic ischemia followed by 55-min reperfusion. hr-EC-SOD C or bovine Cu,Zn-SOD (3 x 10(4) and 6 x 10(4) IU/L, respectively) was added to St. Thomas' Hospital (STH) cardioplegic solution infused 5 min before and 10 min after the ischemic period. Control hearts were treated with STH cardioplegic solution without SOD. By the end of reperfusion, hr-EC-SOD C-treated hearts recovered left ventricular systolic pressure (LVSP), aortic flow (AF) and cardiac output (CO) to 95 +/- 4, 60 +/- 4, 69 +/- 6% of preischemic value, respectively, as compared with 86 +/- 3, 44 +/- 5, and 52 +/- 6% in the control (p < 0.05). Cardioplegia with hr-EC-SOD C significantly reduced lactate dehydrogenase (LDH) release into myocardial effluent during reperfusion (p < 0.05) and increased ATP, AMP, and total creatine (Cr) tissue contents in reperfused hearts (by 21 +/- 3, 42 +/- 4, and 34 +/- 3%, respectively, as compared with control hearts, p < 0.05). The effects of bovine SOD on functional and biochemical indexes were similar but not statistically significant as compared with control. Treatment with hr-EC-SOD C, but not with bovine SOD, resulted in reduction in hydroxyl radical formation assessed by 5-5-dimethy-1-pyrroline-N-oxide spin trap (DMPO) in coronary effluent at early reperfusion with electron spin resonance (ESR) technique. The results suggest that enhanced myocardial protection against ischemia/reperfusion injury afforded by hr-EC-SOD C is related to scavenging of oxygen-derived free radicals.
在离体工作的大鼠心脏上，将人重组C型细胞外超氧化物歧化酶（hr-EC-SOD C）的心脏保护作用与牛铜锌超氧化物歧化酶（bovine Cu,Zn-SOD）的心脏保护作用进行比较。该大鼠心脏先经历35分钟的全心常温缺血，随后再灌注55分钟。在缺血期前5分钟和缺血期后10分钟，将hr-EC-SOD C或牛铜锌超氧化物歧化酶（分别为3×10⁴和6×10⁴ IU/L）添加到圣托马斯医院（STH）心脏停搏液中。对照心脏用不含超氧化物歧化酶的STH心脏停搏液处理。再灌注结束时，hr-EC-SOD C处理的心脏左心室收缩压（LVSP）、主动脉流量（AF）和心输出量（CO）分别恢复到缺血前值的95±4%、60±4%和69±6%，而对照组分别为86±3%、44±5%和52±6%（p<0.05）。用hr-EC-SOD C进行心脏停搏显著减少了再灌注期间乳酸脱氢酶（LDH）释放到心肌流出液中的量（p<0.05），并增加了再灌注心脏中的ATP、AMP和总肌酸（Cr）组织含量（与对照心脏相比分别增加了21±3%、42±4%和34±3%，p<0.05）。与对照相比，牛超氧化物歧化酶对功能和生化指标的影响相似，但无统计学意义。用hr-EC-SOD C处理而非牛超氧化物歧化酶处理，通过电子自旋共振（ESR）技术在再灌注早期用5-5-二甲基-1-吡咯啉-N-氧化物自旋捕获剂（DMPO）评估，导致冠状动脉流出液中羟自由基形成减少。结果表明，hr-EC-SOD C对缺血/再灌注损伤增强的心肌保护作用与清除氧衍生自由基有关。
