Electrophysiological and antiarrhythmic effects of the atrial selective 5-HT(4) receptor antagonist RS-100302 in experimental atrial flutter and fibrillation

Article

关键词: TRANSIENT INWARD CURRENT;    PHARMACOLOGIC CONVERSION;    VENTRICULAR MYOCYTES;    CRUSH-INJURY;    SINUS RHYTHM;    REFRACTORINESS;    QUINIDINE;    PIG;    CARDIOVERSION;    RECURRENCES;   

DOI  :  10.1161/01.CIR.100.19.2010

来源: SCIE

【 摘 要 】

Background-Stimulation of 5-HT(4) receptors increases atrial chronotropic and inotropic responses. Whether other electrophysiological effects are produced is unknown. In humans and swine, 5-HT(4) receptors are present only in atrium. Therefore, the effects of a novel 5-HT(4) receptor antagonist, RS-100302, and the partial agonist cisapride on atrial flutter and fibrillation induced in swine were studied to delineate the role of the 5-HT(4) receptor in modulating atrial electrophysiological properties and the antiarrhythmic potential of RS-100302. Methods and Results-In 17 anesthetized, open-chest, juvenile pigs, atrial flutter or fibrillation was induced by rapid right atrial pacing with or without a right: atrial free wall crush injury, respectively. Atrial effective refractory period (ERP), conduction velocity, wavelength, and dispersion of refractoriness were determined during programmed stimulation via a 56-electrode mapping plaque sutured to the right atrial Free wall. Ventricular electrophysiological parameters were also measured. All electrophysiological parameters were measured at baseline and after infusion of RS-100302 and cisapride. In the atrium, RS-100302 prolonged mean ERP (115 +/- 8 versus 146 +/- 7 ms, P < 0.01) and wavelength (8.3 +/- 0.9 versus 9.9 +/- 0.8 cm, P < 0.01), reduced dispersion of ERP (15 +/- 5 versus 8 +/- 1 ms, P < 0.01), and minimally slowed conduction velocity (72 +/- 4 versus 67 +/- 5 cm/s, P < 0.01). These effects were all partially reversed by cisapride. RS-100302 produced no ventricular electrophysiological effects. RS-100302 terminated atrial flutter in 6 of 8 animals and atrial fibrillation in 8 of 9 animals and prevented reinduction of sustained tachycardia in all animals. Conclusions-The electrophysiological profile of RS-100302 suggests that it may have atrial antiarrhythmic potential without producing ventricular proarrhythmic effects.

【 授权许可】

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