Pharmacological preconditioning strategy based on organ specific mechanisms

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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