Key result
In a swine model, the 5-HT4 receptor antagonist RS-100302 prolonged mean atrial effective refractory period (146 vs 115 ms, P<0.01) and terminated atrial flutter or fibrillation in most animals.
Why the study?
Does RS-100302 alter atrial electrophysiological properties and terminate atrial flutter and fibrillation in a swine model?
Does RS-100302 alter atrial electrophysiological properties and terminate atrial flutter and fibrillation in a swine model?
Answers are grounded in this paper and cite their sources.
The 5-HT4 receptor antagonist RS-100302 demonstrates atrial-selective antiarrhythmic potential by prolonging atrial refractoriness and terminating atrial flutter and fibrillation in a swine model without ventricular proarrhythmic effects.
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.
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Rahme et al. (1999) studied Atrial flutter and fibrillation (n=17). RS-100302 vs. Baseline was evaluated on Atrial effective refractory period (ERP) in ms (p=<0.01). In a swine model, the 5-HT4 receptor antagonist RS-100302 prolonged mean atrial effective refractory period (146 vs 115 ms, P<0.01) and terminated atrial flutter or fibrillation in most animals.
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