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Copyright © 1998 by Institute of Pharmacology Polish Academy of Sciences |
Pol. J. Pharmacol., 1998, 50, 327-331 ISSN 1230-6002 |
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Terikalant modifies the contractility and effective refractory period of heart muscle: comparative study in rats and guinea pigs.
I. KOCIĆ. Pol. J. Pharmacol., 1998, 50, 327-331. The aim of the present study was to examine concentration-dependent effects of terikalant, a blocker of inwardly rectifying K+ currents (IK1), rapidly activated delayed rectifying currents (IKr) and transient outward currents (Ito), on the contractility and effective refractory period in rat and guinea pig isolated papillary muscles. The following parameters were measured: force of contraction (Fc), velocity of contraction (+dF/dt), velocity of relaxation (-dF/dt) and effective refractory period (ERP). ERP was measured indirectly, as the shortest interval between two stimuli S1-S2 inducing an increase in amplitude of force of contraction by at least 25% above baselin value. It has been found that terikalant exerted triphasic effect in the guinea pig preparation. First, a positive inotropic effect and a prolongation of ERP was observed at drug concentrations of 0.03, 0.1 and 0.3 µM. Then, a negative inotropic action was noted at drug concentration of 1 µM in comparison with the maximum positive inotropic action, without significant effect on ERP duration. Subsequently, a positive inotropic action at drug concentrations of 3 and 10 µM and significant prolongation of ERP were detected in comparison with the effects obtained at 1 µM concentration. In rat preparations, however, terikalant had no effect on the contractility and the duration of ERP in the concentration range from 0.03 to 1 µM. At 1 and 3 µM, a tendency to the negative inotropic action was observed, but the results were not significantly different as compared with the control value. At 10 µM, a significant positive inotropic action and prolongation of ERP duration occured, in comparison with the control values as well as the values obtained at terikalant concentration of 1 µM. These differences in the effects of terikalant in guinea pig and rat papillary muscles are probably due to the species differences, especially to a lack of functional IK current in rat heart. Key words: terikalant, contractility, papillary muscle, effective refractory period |
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