A Novel Bisindolylmaleimide Derivative Enhances Functional Recovery of Heart After Long-Term Hypothermic Heart Preservation
A Novel Bisindolylmaleimide Derivative Enhances Functional Recovery of Heart After Long-Term Hypothermic Heart Preservation
复制标题
DOI：
10.1097/01.tp.0000267019.93796.aa
复制
发表时间：
2007-06
期刊：
影响因子：
6.2
通讯作者：
R. Katare;Zhitian Zou;M. Sodeoka;S. Sasaguri
中科院分区：
文献类型：
--
作者：
R. Katare;Zhitian Zou;M. Sodeoka;S. Sasaguri
背景心脏移植后的功能恢复主要取决于保存液在保存和再灌注过程中提供物理和生化环境以维持组织活力的能力。在这里，我们证明了一种新的双吲哚马来酰亚胺衍生物，MS 1，对增强功能恢复的心脏后，长期低温保存时，加入到防腐剂溶液的保护作用。方法.在麻醉和人工通气后，将心脏快速分离并在37°C下以工作模式用Kreb’s Henseleit缓冲液灌注。灌注30分钟后，用心脏停搏液将心脏停搏，并在4°C下在含有（UW-MS 1组）或不含MS 1（UW-载体组）的威斯康星州大学溶液中保存12小时。12小时后，心脏再灌注60分钟。结果MS 1处理的心脏显示：a）心脏功能的显著恢复（P<0.001），B）良好保存的心肌ATP水平（P<0.001），c）较少的心肌水含量（P<0.01），d）减少的氧化应激（P<0.001），e）较少的细胞内肿胀和良好保存的线粒体，以及g）与保存在不含MS 1的UW溶液中的对照心脏相比，细胞存活级联的激活。与此相反，这些保护作用的MS 1取消开放的渗透性转换孔前MS 1处理。结论这些结果共同表明该化合物在保护心肌免受再灌注损伤方面的功效，从而使该药物成为心脏手术后经历再灌注的患者的临床有用工具。
Background. Functional recovery following heart transplantation mainly depends on the ability of preservative solution in providing the physical and biochemical environment so as to maintain the viability of the tissue during preservation and in reperfusion. Here we demonstrate the protective effects of a novel bisindolylmaleimide derivative, MS1, on enhancing the functional recovery of the heart following long-term hypothermic preservation when added to the preservative solution. Methods. After anesthesia and artificial ventilation, the hearts were rapidly isolated and perfused with Kreb’s Henseleit buffer at 37°C in working mode. After 30 minutes of perfusion, the hearts were arrested with cardioplegic solution and preserved in University of Wisconsin solution with (UW-MS1 group) or without MS1 (UW-Vehicle group) for 12 h at 4°C. After 12 hours, the hearts were reperfused for 60 minutes. Results. MS1 treated hearts showed: a) significant recovery of cardiac functions (P<0.001), b) well-preserved myocardial ATP levels (P<0.001), c) less myocardial water content (P<0.01), d) reduced oxidative stress (P<0.001), e) less intracellular swelling and well-preserved mitochondria, and g) activation of cell survival cascades compared to the control hearts preserved in UW solution without MS1. In contrast, these protective effects of MS1 were abolished on opening the permeability transition pore before MS1 treatment. Conclusion. These results altogether indicate the efficacy of this compound in protecting the myocardium against reperfusion injury and thus making this drug a clinically useful tool in patients undergoing reperfusion after cardiac surgeries.