The cardioprotective effects of volatile anesthetics on the canine Ischemic myocardium : an analysis of its mechanism in relation to changes in K_<ATP> channel activity and blood ionized magnesium level.

挥发性麻醉药对犬缺血性心肌的心脏保护作用：分析其与 K_<ATP> 通道活性和血液离子镁水平变化相关的机制。

• 批准号: 10671441
• 负责人: AKAZAWA Satoshi
• 金额: $ 2.3万
• 依托单位: Jichi Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671441/
• 关键词: K_<ATP> channel; agonist; volatile anesthetics; glyburide; sevoflurane; antagonist; regional myocardial function; myocardial stunning; KATPチャネル; 局所心筋収縮機能; 再灌流障害; 抗虚血作用; 心機能; 虚血プレコンディショニング; K_<ATP>チャネル開口薬; マグネシウムイオン; K_<AIP>チャネル開口薬; ニコランジル

Background : Volatile anesthetics have been shown to protect against myocardial ischemia and reperfusion injury in animals. However, the mechanism of the protective actions of these agents has not been elucidated. This study investigated the role of myocardial adenosine triphosphate-regulated potassium [K_<ATP>] channels in sevoflurane-induced enhancement of regional myocardial contractile function after multiple brief occlusions and reperfusion of the left anterior descending coronary artery (LAD) in fentanyl-anesthetized dogs.Methods : Twenty-one dogs were allocated to one of three groups (n = 7 for each). In control group, dogs received drug vehicle alone. In the other two groups, dogs received vehicle or glyburide (a non-selective K_<ATP> channel antagonist (1.0 mg/kg i.v.) immediately before inhalation of 1 minimum alveolar concentration of sevoflurane administered for 30 min before and during ischemia. Sevoflurane was discontinued at the onset of the final reperfusion period. Reg … More ional myocardial contractile function was assessed with percent segment shortening (%SS). Measurements of hemodynamics and %SS were made before and during ischemia, and during 180 min of reperfusion.Results : LAD occlusion caused regional dyskinesia during ischemia in all dogs. Dogs receiving glyburide plus sevoflurane showed poor recovery of %SS by 180 min after reperfusion (approximately 50 % of baseline). In contrast, dogs receiving vehicle plus sevoflurane demonstrated almost complete recovery of %SS by 180 min after reperfusion (90 % of baseline). Control dogs showed an intermediate recovery of %SS between the other two groups. Sevoflurane reduced myocardial oxygen demand through decreases in aortic pressure and heart rate in vehicle-pretreated dogs.Conclusion: The results indicate that sevoflurane protect against regional myocardial contractile dysfunction caused by myocardial stunning. These actions result in enhanced recovery of contractile function of post-ischemic, reperfused myocardium and are mainly mediated by sevoflurane-induced activation of K_<ATP> channels. Cardioprotective interaction between sevoflurane and magnesium should be determined in a further study. Less

背景：挥发性麻醉药已被证明对动物心肌缺血和再灌注损伤具有保护作用。然而，这些药物的保护作用机制尚未阐明。本研究观察了<ATP>芬太尼麻醉犬冠状动脉左前降支（LAD）多次短暂阻断再灌注后，心肌腺苷三磷酸钾通道（ATP K_2）在七氟醚增强局部心肌收缩功能中的作用。在对照组中，犬仅接受药物载体。另两组分别给予溶剂或非选择性钾通道拮抗剂格列本脲<ATP>（1.0mg/kg，i. v.）在缺血前和缺血期间吸入1个最小肺泡浓度的七氟烷30分钟。在最终再灌注期开始时停用七氟烷。Reg ...更多信息 用节段缩短率（%SS）评价心肌收缩功能。在缺血前、缺血过程中和再灌注180 min期间测量血流动力学和%SS。接受格列本脲+七氟烷的犬在再灌注后180 min时显示%SS恢复较差（约为基线的50%）。相比之下，接受溶剂加七氟烷的犬在再灌注后180 min时显示%SS几乎完全恢复（基线的90%）。对照犬的%SS回收率介于其他两组之间。七氟烷通过降低主动脉压和心率降低心肌需氧量在车辆预处理dogs.Conclusion：结果表明，七氟烷保护区域心肌收缩功能障碍引起的心肌顿抑。这些作用主要通过七氟醚激活钾通道而介导，从而促进缺血后再灌注心肌收缩功能的恢复<ATP>。应在进一步研究中确定七氟烷和镁之间的神经保护相互作用。少