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Effects of ibutilide on inhibiting heart rate and rapidly terminating atrial flutter in canine.

Cell biochemistry and biophysics (2010-10-26)
Jianling Sun, Xiaoying Li, Jihong Guo, Peng Liu, Ping Zhang
RÉSUMÉ

Ibutilide is a newer class-III antiarrhythmic agent approved for clinical use. We sought to investigate its electrophysiological effects in canines and also the underlying mechanism of conversion of atrial flutter (AFL). For this purpose, 15 male mongrel dogs were anesthetized, intubated with tracheal tube, and heart was exposed and connected to electrodes. Electrophysiologic variables were measured with and without ibutilide (10-min infusion-dose: 0.10 mg/kg; 30-min later, maintaining dose: 0.01 mg/min) which included heart rate, conduction of intra- and inter-atrium, conduction ratio of isthmus, and ERP. Ibutilide had a significant inhibitory effect on sinus atrial node, peak response time was 20-30 min, and heart rate returned to the baseline after 2 h. One canine had 5 s sinus pause, and the other had 2:1 atrioventricular conduction post-administration. Atrial, ventricular, and pulmonary vein ERP was significantly prolonged (P < 0.05). No significant differences were observed regarding conduction of intra-atrium, inter-atrium, and isthmus. It was, therefore, concluded that ibutilide had suppressive effect on sinus atrial and atrioventricular nodes. Ibutilide rapidly terminated AFL due to the reentrant wave front's inability to proceed as the refractory period was protracted and hence caused the whole excitable gap of the reentrant circuit to be affected by refractoriness.

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Sigma-Aldrich
Ibutilide hemifumarate salt, ≥98% (HPLC)