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The Na+-Ca2+ exchange (NCX) system plays a pivotal role in regulating intracellular Ca2+ concentration in cardiomyocytes, neuronal cells, kidney and a variety of other cells. It performs a particularly important function in regulating cardiac contractility and electrical activity. One of the leading NCX inhibitors is KB-R9743 (KBR) that appears to exhibit(More)
Isolated preparations of atrial specialized conduction fibers ("plateau" fibers) qualitatively resembled ventricular Purkinje fibers (false tendons) in their response to acetylstrophanthidin. Acetylstrophanthidin in concentrations of 1-3 X 10~ 7 g/ml caused coupled, frequency-dependent transient depolarizations (TDs) in both types of fiber. In free-running(More)
A simple in vivo closed-chest atrial fibrillation (Af) model of rats was developed. Af was reproducibly induced by transesophageal atrial burst pacing for 30 s in each of the pentobarbital-anesthetized rats, whereas the cardiohemodynamic condition as well as the inducibility and duration of Af episode was stable over time. Moreover, the anti-Af effect of(More)
SEA0400 (2-[4-[(2,5-difluorophenyl)methoxy]phenoxy]-5-ethoxyaniline), a novel and selective inhibitor of Na+/Ca2+ exchanger, was investigated for its possible antiarrhythmic effects on arrhythmias of Ca2+ overload induced by coronary ligation/reperfusion and by digitalis in the dog. SEA0400 (1.0 mg/kg) did not change the hemodynamics but slightly prolonged(More)
The present study was designed to investigate what kinds of adaptation occurred in the canine chronic AV block model, which has been used to study torsade de pointes (TdP). Dogs at 7-10 days (acute phase) and 28-56 days (chronic phase) after AV block were assessed. Ventricular effective refractory period and monophasic action potential duration were(More)
This study was designed to assess the effects of typical class I drugs on the terminal repolarization process of the in situ heart, which is a useful marker of the potential of drug-induced long QT syndrome. Disopyramide (0.3 and 3.0 mg/kg per 10 min, n = 6) or mexiletine (0.3 and 3.0 mg/kg per 30s, n = 6) was intravenously administered to(More)
The effects of a typical I(Kr) channel blocker sematilide on the relationship between ventricular repolarization, refractoriness and onset of torsades de pointes (TdP) were studied using the canine isolated, blood-perfused ventricular septum preparation with monophasic action potential (MAP) recording. Intracoronary infusion of sematilide (10-100(More)
Although a second-generation histamine H(1) blocker terfenadine induced torsades de pointes (TdP) arrhythmias in patients via the blockade of a rapid component of delayed rectifier K(+) current (I(Kr)), such action of terfenadine has not been detected in previous animal models. We analysed the potential of the canine persistent atrioventricular block heart,(More)
The effects of famotidine on the cardiac repolarization process were assessed using four different levels of test systems described in the draft stage guideline ICH S7B. A supratherapeutic concentration of famotidine (10(-5) M), which is >8 times higher than C(max) obtained after its therapeutic dose, neither inhibited human ether-a-go-go-related gene(More)
Catheter ablation of the atrioventricular node (AVN) with radiofrequency current is closely associated with the short-term onset of a junctional rhythm. The origin of this rhythm was analyzed in Beagle dogs which were anesthetized with pentobarbital sodium. Atrioventricular (AV) conduction block was induced first using a standard catheter ablation technique(More)