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.

背景：研究表明，挥发性麻醉药对动物心肌缺血再灌注损伤有保护作用。然而，这些保护剂的保护作用机制尚不清楚。本研究在芬太尼麻醉犬冠状动脉左前降支(LAD)多次短暂阻断再灌流后，观察心肌细胞三磷酸腺苷调节钾通道在七氟醚增强心肌局部收缩功能中的作用。对照组只接受药物载体治疗。另两组分别给予赋形剂或格列本脲(一种非选择性钾通道拮抗剂)(1.0 mg/kg静脉注射)。吸入前即刻给予七氟醚肺泡内最低浓度为1的七氟醚，持续30分钟。七氟醚在最后再灌注期开始时停用。REG…用节段缩短百分比(%SS)评价更多的离子心肌收缩功能。分别在缺血前、缺血时和再灌流180min内测定血流动力学和%SS。结果：所有犬在缺血期均出现局部运动障碍。接受格列本脲加七氟醚治疗的犬在再灌流后180分钟显示%SS恢复较差(约为基线的50%)。相比之下，接受七氟醚加安慰剂的犬在再灌流180min时%SS几乎完全恢复(基线的90%)。对照组犬的%SS在其他两组之间有中等程度的恢复。结论：七氟醚对心肌顿抑所致的局部心肌收缩功能障碍具有保护作用。这些作用可促进缺血再灌流后心肌收缩功能的恢复，这些作用主要通过七氟醚激活K&lt；ATP&gt；通道而实现。七氟醚和镁之间的心脏保护作用应在进一步的研究中确定。较少

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