Myers C L, Weiss S J, Kirsh M M, Shepard B M, Shlafer M
J Thorac Cardiovasc Surg. 1986 Feb;91(2):281-9.
We evaluated whether supplemental pharmacologic interventions that altered formation or degradation of reactive oxygen metabolites, when added to hypothermic crystalloid cardioplegic solution (procaine-free St. Thomas' Hospital solution), alter postischemic function of isolated rabbit hearts. Hypoxic, substrate-free cardioplegic solutions cooled to 27 degrees C were perfused through isolated rabbit hearts for 5 minutes before and after an uninterrupted 2 hour period of global ischemia at 27 degrees C. Hearts were then reperfused with standard buffer for 1 hour at 37 degrees C. In some experiments, the cardioplegic solution was supplemented with the following: superoxide dismutase (30 micrograms/ml; degrades superoxide anion); catalase (1.7 micrograms/ml; degrades hydrogen peroxide); allopurinol (1 mmol/L; inhibits xanthine oxidase); or deferoxamine (Desferal, 0.5 mmol/L; selectively chelates ferric iron). Postreperfusion contractile parameters of supplemented hearts, including left ventricular pressure development and its first derivative, left ventricular compliance, spontaneous heart rate, and coronary vascular resistance, were statistically compared to data obtained from hearts arrested with unsupplemented cardioplegic solution. Catalase supplementation provided statistically significant improvement of most functional parameters; somewhat less protection was obtained with allopurinol. Deferoxamine provided little added protection except for the ability to prevent ischemia-induced increases of coronary vascular resistance. There was no evidence of added protection by superoxide dismutase. The data suggest that an important component of ischemia-induced cardiac cell damage in an asanguineous setting is hydrogen peroxide-dependent, and interventions that either inhibit production of superoxide anion or degrade hydrogen peroxide offer best protection. They may be clinically efficacious additives to crystalloid cardioplegic solutions.
我们评估了在低温晶体心脏停搏液（不含普鲁卡因的圣托马斯医院溶液）中添加改变活性氧代谢产物形成或降解的补充性药物干预措施，是否会改变离体兔心缺血后的功能。在27℃下对离体兔心进行2小时持续性全心缺血前后，将冷却至27℃的缺氧、无底物心脏停搏液灌注通过离体兔心5分钟。然后在37℃下用标准缓冲液对心脏进行1小时再灌注。在一些实验中，心脏停搏液补充了以下物质：超氧化物歧化酶（30微克/毫升；降解超氧阴离子）；过氧化氢酶（1.7微克/毫升；降解过氧化氢）；别嘌呤醇（1毫摩尔/升；抑制黄嘌呤氧化酶）；或去铁胺（去铁敏，0.5毫摩尔/升；选择性螯合三价铁）。将补充药物后心脏再灌注后的收缩参数，包括左心室压力上升及其一阶导数、左心室顺应性、自发心率和冠状血管阻力，与用未补充药物的心脏停搏液停搏的心脏所获得的数据进行统计学比较。补充过氧化氢酶在统计学上显著改善了大多数功能参数；别嘌呤醇提供的保护作用稍弱。除了能够防止缺血诱导的冠状血管阻力增加外，去铁胺几乎没有提供额外的保护作用。没有证据表明超氧化物歧化酶能提供额外的保护作用。数据表明，在无血环境中缺血诱导的心肌细胞损伤的一个重要成分是依赖过氧化氢的，抑制超氧阴离子产生或降解过氧化氢的干预措施提供了最佳保护。它们可能是晶体心脏停搏液临床上有效的添加剂。
