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：挥发性麻醉剂对动物心肌缺血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。本研究探讨了芬太尼麻醉犬左冠状动脉前降支（LAD）多次短暂闭塞再灌注后，七氟醚诱导心肌三磷酸腺苷调节的钾通道[K_<ATP>]在心肌局部收缩功能增强中的作用。方法：21只狗随机分为3组，每组7只。对照组犬只接受药物载药。在其他两组中，狗在缺血前30分钟和30分钟内立即吸入1个最低肺泡浓度的七氟醚，然后立即接受载体或格列本脲(一种非选择性K_<ATP>通道拮抗剂（1.0 mg/kg静脉注射）。在最后再灌注期开始时停用七氟醚。以节段缩短百分比（%SS）评价局部心肌收缩功能。在缺血前、缺血中、再灌注180 min时测量血流动力学和%SS。结果：LAD闭塞导致所有犬缺血时出现局部运动障碍。接受格列本脲加七氟醚治疗的犬在再灌注后180分钟（约为基线的50%），%SS恢复较差。相比之下，接受载药加七氟醚的狗在再灌注后180分钟几乎完全恢复了%SS（基线的90%）。对照犬在其他两组之间显示了%SS的中间恢复。七氟醚通过降低车辆预处理犬的主动脉压和心率来降低心肌耗氧量。结论：七氟醚对心肌休克引起的局部心肌收缩功能障碍有保护作用。这些作用主要通过七氟醚诱导的K_<ATP>通道激活介导，可增强缺血后再灌注心肌的收缩功能恢复。七氟醚和镁之间的心脏保护相互作用有待进一步研究。少