Pharmacological control of myocardial contractile function on myocardial stunning

本研究旨在探讨心肌顿抑的机制，建立心肌顿抑的计算机心血管测量系统，包括分析左心室压力-容量关系。观察七氟醚或Na~+/Ca~(2+)交换抑制剂KB-R7943对犬心肌顿抑的血流动力学和心脏保护作用。七氟醚通过激活线粒体KATP通道发挥心脏保护作用，且与冠脉血流量或心脏做功减少无关。KB-R7943以剂量依赖的方式改善缺血再灌注后的心肌收缩功能障碍，对冠脉和全身血流动力学无影响。采用犬冠状动脉微栓塞术模型，观察异丙酚对犬急性缺血心肌收缩功能和氧平衡的影响。异丙酚引起的收缩…下降幅度更大丙泊酚的作用机制与氧失衡无关，谷氧还蛋白过表达可通过调节Akt的氧化还原状态来保护心肌免受过氧化氢诱导的细胞凋亡。谷氧还蛋白在保护心肌免受氧化应激中起着重要作用，我们观察了丹曲林在异丙酚麻醉中的血流动力学作用。丹曲林可逆转异丙酚的降压作用，增加冠脉血流量，降低冠脉阻力。我们观察了右旋美托咪定和异丙酚对静脉注射异丙肾上腺素引起的心率反应的影响。右旋美托咪定而非异丙酚可提高持续静脉滴注异丙肾上腺素的心率反应。我们研究了钙增敏剂MCI-154和异氟醚在药物自主神经系统活动阻断后对慢性仪器化犬心肌收缩性能的影响。在清醒状态和异氟醚麻醉期间，在不改变计算的心肌耗氧量的情况下，MCI-154可增加心肌收缩能力和降低冠脉血管阻力。较少

This study was carried out to investigate the mechanisms of myocardial stunning and to establish the pharmacological therapeutic method for myocardial stunning using the computer-based cardiovascular measurement system including the analysis of left ventricular pressure-volume relationship.We investigated the hemodynamic and cardioprotective effects of sevoflurane or KB-R7943, a Na^+/Ca^<2+> exchanger inhibitor, on myocardial stunning in dogs. Sevoflurane has a cardioprotective effect mediated through activation of mitochondrial KATP channels and independent of coronary blood flow or reduction in cardiac work. KB-R7943 improves myocardial contractile dysfunction after ischemia-reperfusion in a dose-dependent, manner, and has no effect on coronary and systemic hemodynamics. We investigated the effects of propofol on myocardial contractility and oxygen balance in acute ischemic myocardium, using coronary microembolization model in dogs. Propofol causes a greater decrease in the contracti … More lity of acute ischemic myocardium as compared with normal myocardium, and oxygen imbalance is not involved in the mechanism of this propofol's action.We demonstrated that overexpression of Glutaredoxin protected myocardium from hydrogen peroxide-induced apoptosis by regulating the redox state of Akt. Glutaredoxin plays an important role in protecting myocardium from oxidative stress.We investigated the hemodynamic actions of dantrolene during propofol anesthesia. Dantrolene reverses the hypotensive action produced by propofol and causes an increase in coronary blood flow with a decrease in coronary vascular resistance. We investigated the effects of dexmedetomidine and propofol on the response of heart rate to intravenous isoproterenol. Dexmedetomidine but not propofol enhances the heart rate response to the continuous intravenous infusion of isoproterenol. We investigated the interaction of MCI-154, a calcium sensitizer, and isoflurane on myocardial contractility in chronically instrumented dogs after pharmacological autonomic nervous system activity blockade. MCI-154 increases myocardial contractility and decreases coronary vascular resistance without changing calculated myocardial oxygen consumption during both the conscious state and isoflurane anesthesia. Less