Menasche P, Grousset C, Gauduel Y, Mouas C, Piwnica A
Service de Chirurgie Cardio-Vasculaire, Hôpital Lariboisière, Paris, France.
Circulation. 1987 Nov;76(5 Pt 2):V180-5.
The hydroxyl radical is one of the most damaging oxygen metabolites that are thought to be produced during ischemia and reperfusion of cardiac tissue. Therefore, we used the isolated, isovolumetric, buffer-perfused rat heart preparation of cardioplegic arrest to assess the effects of interventions targeted at inhibiting production of the hydroxyl radical by decreasing either the availability of one of its precursors (hydrogen peroxide) or that of the metal catalyst (ferric iron) involved in the radical formation. Sixty hearts were studied and, except for nonischemic controls, were subjected to 3 hr of hypothermic (15 degrees to 18 degrees C) cardioplegic arrest, followed by 45 min of reperfusion. The following interventions were tested: pretreatment with peroxidase, a scavenger of hydrogen peroxide, pretreatment with a combination of peroxidase and the iron chelator deferoxamine, pretreatment with peroxidase followed by supplementation of the cardioplegic solution with deferoxamine, and supplementation of the cardioplegic solution with deferoxamine without preischemic enzymatic treatment. Based on comparisons of postreperfusion pressure development, maximal ventricular dP/dt, left ventricular compliance, and coronary flow, deferoxamine-containing cardioplegic solution alone afforded the best myocardial protection. This may be due to the ability of deferoxamine to act both as an iron chelator and as a direct scavenger of superoxide anion, an activated oxygen species that participates in hydroxyl radical formation. This study confirms that an important component of the cardiac damage sustained during global ischemia and reperfusion may involve injury caused by the hydroxyl radical. Furthermore, our results point out the potential therapeutic usefulness of deferoxamine in the context of cardioplegic protection during open-heart procedures.
羟自由基是在心脏组织缺血和再灌注过程中产生的最具破坏性的氧代谢产物之一。因此，我们使用离体的、等容的、缓冲液灌注的大鼠心脏停搏液灌注制备模型，来评估通过减少其前体之一（过氧化氢）或参与自由基形成的金属催化剂（三价铁）的可用性来抑制羟自由基产生的干预措施的效果。研究了60颗心脏，除了非缺血对照组外，其余心脏均经历3小时低温（15摄氏度至18摄氏度）心脏停搏，随后再灌注45分钟。测试了以下干预措施：用过氧化氢清除剂过氧化物酶预处理、用过氧化物酶和铁螯合剂去铁胺联合预处理、用过氧化物酶预处理后在心脏停搏液中补充去铁胺，以及在没有缺血前酶处理的情况下在心脏停搏液中补充去铁胺。基于对再灌注后压力发展、最大心室dP/dt、左心室顺应性和冠状动脉血流的比较，单独含去铁胺的心脏停搏液提供了最佳的心肌保护。这可能是由于去铁胺既能作为铁螯合剂，又能作为超氧阴离子（一种参与羟自由基形成的活性氧）的直接清除剂。这项研究证实，在全心缺血和再灌注期间持续的心脏损伤的一个重要组成部分可能涉及羟自由基引起的损伤。此外，我们的结果指出了去铁胺在心脏直视手术中停搏液保护方面的潜在治疗用途。
