Pharmacological preconditioning strategy based on organ specific mechanisms

为探讨药物预处理对心肌和肾脏缺血-再灌注损伤的作用机制，建立缺血-再灌注损伤的药物治疗方法，本研究采用慢性机械负荷犬，观察了MCI-154和异氟醚对药物阻断自主神经活性后心肌收缩力的相互作用。MCI-154在清醒状态和异氟烷麻醉期间增加心肌收缩力并降低冠状血管阻力，而不改变计算的心肌耗氧量。我们研究了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。KB-R7943以剂量依赖性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。我们检查了米里诺的保护作用， 关于我们 临床剂量的NE使用麻醉猪的心肌顿抑模型。在缺血前或再灌注后立即给予米力农可保护缺血-再灌注诱导的心肌顿抑。采用犬冠状动脉微栓塞模型，观察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，丙泊酚可使急性缺血心肌的收缩力显著降低，氧失衡与丙泊酚的作用机制无关。我们研究了右美托咪定是否对缺氧-复氧诱导的左心室功能障碍具有直接保护作用，而无全身血流动力学和体液效应。右美托咪定主要通过α 2-肾上腺素能刺激对缺氧复氧所致的左心室功能障碍发挥直接保护作用。我们研究了磷酸二酯酶III型抑制剂奥普力农对大鼠心肌梗死的保护作用。本实验通过对大鼠肾脏缺血/再灌注损伤的药理学预处理研究发现，异氟醚预处理对大鼠肾脏缺血/再灌注损伤具有保护作用，其机制可能与其激活PI 3 K-Akt和抑制mPTP有关。JNK和ERK蛋白激酶的抑制可能参与了异氟醚预处理的机制。少

This study was carried out to investigate the mechanisms of pharmacological preconditioning effects against myocardial and renal ischemia-reperfusion injury and to establish the pharmacological therapeutic method for ischemia-reperfusion injury.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. We investigated the hemodynamic and cardioprotective effects of KB-R7943, a Na+/Ca2+ exchanger inhibitor, on myocardial stunning in dogs. KB-R7943 improves myocardial contractile dysfunction after ischemia-reperfusion in a dose-dependent manner, and has no effect on coronary and systemic hemodynamics. We examined protective effects of milrino … More ne in a clinical dose using the myocardial stunning model of anesthetized swine. Milrinone administered before ischemia or just after reperfusion provides protection against ischemia-reperfusion-induced myocardial stunning. 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 contractility of acute ischemic myocardium as compared with normal myocardium, and oxygen imbalance is not involved in the mechanism of this propofol's action. We investigated to determine whether dexmedetomidine has a direct protective effect against hypoxia-reoxygenation-induced left ventricular dysfunction without systemic hemodynamic and humoral effects in isolated rat hearts. Dexmedetomidine exerts the direct protective effect on the left ventricular dysfunction caused by hypoxia-reoxygenation through mainly alpha 2-adrenergic stimulation. We investigated the cardioprotective effects of olprinone, a phosphodiesterase type III inhibitor, on myocardial infarction in rats. The olprinone-induced cardioprotective effect could be exerted via the activation of PI3K-Akt and the inhibition of mPTP during early reperfusion.We investigated pharmacological preconditioning by isoflurane in the rat kidney, isoflurane has a preconditioning effect against renal ischemia/reperfusion injury when administered before ischemia. Inhibition of the protein kinases, JNK and ERK, might be involved in the mechanisms of isoflurane preconditioning. Less