Pharmacological control of myocardial contractile function on myocardial stunning

本研究利用基于计算机的心血管测量系统，包括左心室压力-容积关系分析，探讨心肌休克的发生机制，建立心肌休克的药物治疗方法。我们研究了七氟醚或KB-R7943（一种Na^+/Ca^<2+>交换抑制剂）对狗心肌休克的血流动力学和心脏保护作用。七氟醚具有通过激活线粒体KATP通道介导的心脏保护作用，不依赖于冠状动脉血流量或心脏功的减少。KB-R7943以剂量依赖的方式改善缺血-再灌注后心肌收缩功能障碍，对冠状动脉和全身血流动力学无影响。采用犬冠状动脉微栓塞模型，研究异丙酚对急性缺血心肌收缩力和氧平衡的影响。与正常心肌相比，异丙酚可使急性缺血心肌收缩性下降更大，氧不平衡与异丙酚作用机制无关。我们证明了Glutaredoxin的过表达通过调节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。Glutaredoxin在保护心肌免受氧化应激中起重要作用。研究异丙酚麻醉时丹曲林的血流动力学作用。丹曲林逆转异丙酚产生的降压作用，导致冠状动脉血流量增加，冠状动脉血管阻力降低。我们研究了右美托咪定和异丙酚对静脉注射异丙肾上腺素的心率反应的影响。右美托咪定而非异丙酚可增强持续静脉输注异丙肾上腺素的心率反应。我们研究了MCI-154（一种钙增敏剂）和异氟醚对长期使用药物阻断自主神经系统活性的狗心肌收缩力的相互作用。在意识状态和异氟醚麻醉下，MCI-154在不改变计算心肌耗氧量的情况下增加心肌收缩力，降低冠状血管阻力。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