Endogenous nitric oxide is involved in post-ischemic functional recovery induced by adenosine-enhanced ischemic preconditioning.

内源性一氧化氮参与腺苷增强缺血预处理诱导的缺血后功能恢复。

• 批准号: 13671397
• 负责人: YANO Mitsuhiro
• 金额: $ 0.51万
• 依托单位: University of Miyazaki(Miyazaki Medical College)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671397/
• 关键词: Adenosine-enhansed Ischemic Preconditioning; Ischemia-Reperfusion Injury; Cardioprotection; nitric oxide; Isolated Heart Perfusion; Adenosine-enhanced Ischemic Preconditioning

The precise mechanism of cardioprotection afforded by adenosine-enhanced ischemic preconditioning (APC) remains unknown. The present study examines whether endogenous nitric oxide (NO) contributes to post-ischemic functional recovery during early reperfusion in the rabbit heart treated by APC. Langendorff perfused hearts underwent global ischemia for 30 minutes followed by reperfusion for 120 minutes. Hemodynamic parameters and NO concentrations were determined during reperfusion. The hearts were separated into groups as follows : perfusion without global ischemia for 180 minutes (Control) ; global ischemia and reperfusion (GI group) ; 5 minutes of global ischemia followed by 5 minutes of reperfusion then 30 minutes of global ischemia and 120 minutes of reperfusion (ischemic preconditioned (IPC) group) ; a 10 ml bolus injection of 1 mmol/L adenosine immediately before IPC (APC group) ; APC plus NG -Nitro-L-arginine methyl ester (L-NAME) for first 30 minutes of reperfusion (L-NAME group). The first derivative of left ventricular pressure, left ventricular end-diastolic pressure and coronary flow were significantly improved in the APC group as compared with the GI and IPC groups (p < 0.05). The NO concentration was significantly increased in the APC group compared with the other groups after 10 minutes of reperfusion (p < 0.05). These effects were abolished by NO synthase inhibition using L-NAME. Our results suggested that endogenous NO is involved in the post-ischemic functional recovery of the heart afforded by APC.

腺苷增强缺血预处理（APC）提供心脏保护的确切机制仍不清楚。本研究探讨内源性一氧化氮 (NO) 是否有助于 APC 治疗的兔心脏早期再灌注期间的缺血后功能恢复。 Langendorff 灌注心脏经历 30 分钟的整体缺血，然后再灌注 120 分钟。再灌注期间测定血流动力学参数和NO浓度。将心脏分为如下组：灌注180分钟，无整体缺血（对照）；全局缺血和再灌注（GI组）； 5分钟整体缺血，随后5分钟再灌注，然后30分钟整体缺血和120分钟再灌注（缺血预处理（IPC）组）； IPC前立即推注10ml 1mmol/L腺苷（APC组）； APC 加 NG-硝基-L-精氨酸甲酯 (L-NAME) 用于再灌注前 30 分钟（L-NAME 组）。与 GI 和 IPC 组相比，APC 组的左心室压力、左心室舒张末期压力和冠脉流量的一阶导数显着改善（p < 0.05）。再灌注10分钟后，与其他组相比，APC组的NO浓度显着升高（p < 0.05）。使用 L-NAME 抑制 NO 合酶可以消除这些影响。我们的结果表明内源性 NO 参与 APC 提供的心脏缺血后功能恢复。