Ischemic preconditioning and nicorandil pretreatment improve donor heart preservation.

Zhiwei Zhang, Toshio Kaneda, Kwansong Ku, Masaki Otaki, Hidetaka Oku
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引用次数: 9

Abstract

The present study investigated the effects of ischemic preconditioning (IPC) and nicorandil pretreatment on myocardial storage in a donor heart preservation model. Isolated rat hearts were separated into groups: group 1, non-preconditioned control group; group 2, 2.5 min of normothermic ischemia followed by 15 min of normothermic Langendorff perfusion (one IPC cycle); and group 3, 2 cycles of IPC. All hearts were subsequently stored in University of Wisconsin solution at 4 degrees C for 2, 4 and 6h, and the concentrations of high-energy phosphate metabolites were measured for each time point. Heart function parameters (aortic flow, coronary flow and cardiac output) were measured when the heart was reperfused following the 2, 4 or 6 h of preservation. The effects of nicorandil, an ATP-sensitive potassium channel opener, on heart function following preservation were also evaluated. Nicorandil was injected intravenously before heart harvesting. The results showed that the energy status was well preserved in the IPC groups. The 2-cycle IPC group showed better recovery of heart function following preservation. Pretreatment with nicorandil also improved functional recovery of the heart following preservation. The present study showed that IPC of the rat heart resulted in improved myocardial energy metabolism and functional recovery after hypothermic preservation, and that nicorandil has potential for pharmacological preconditioning in heart preservation for transplantation.
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缺血预处理和尼可地尔预处理可改善供体心脏保存。
本研究探讨了缺血预处理(IPC)和尼可地尔预处理对供体心脏保存模型心肌储存的影响。将离体大鼠心脏分为两组:1组为非预处理对照组;2组:常温缺血2.5 min后进行常温Langendorff灌注15 min(1个IPC周期);第3组,2个IPC周期。所有心脏随后在威斯康星大学溶液中4℃保存2、4和6小时,并在每个时间点测量高能磷酸盐代谢物的浓度。保存2、4、6小时后心脏再灌注时测量心功能参数(主动脉流量、冠状动脉流量和心输出量)。还评估了尼可地尔(一种atp敏感的钾通道打开剂)对保存后心脏功能的影响。在心脏摘取前静脉注射尼可地尔。结果表明,IPC组的能量状态得到了较好的保存。2周期IPC组保存后心功能恢复较好。尼可地尔预处理也能改善心脏保存后的功能恢复。本研究表明,大鼠心脏低温保存后,IPC可改善心肌能量代谢和功能恢复,尼可地尔在移植心脏保存中具有药理预处理的潜力。
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