多非利特与雷诺嗪联合应用于马急性诱导心房颤动模型的抗心律失常作用。

Antiarrhythmic Effects of Combining Dofetilide and Ranolazine in a Model of Acutely Induced Atrial Fibrillation in Horses.

机构信息

Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark. Dr. Haugaard is now with Department of Experimental Medicine, University of Copenhagen, Copenhagen, Denmark.

Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

出版信息

J Cardiovasc Pharmacol. 2018 Jan;71(1):26-35. doi: 10.1097/FJC.0000000000000541.

BACKGROUND

Antiarrhythmic compounds against atrial fibrillation (AF) often have reduced efficacy and may display cardiac and/or noncardiac toxicity. Efficacy can be improved by combining 2 compounds with distinct mechanisms, and it may be possible to use lower doses of each compound, thereby reducing the likelihood of adverse side effects. The purpose of this study was to investigate whether the effective doses of dofetilide and ranolazine can be reduced if the drugs are combined.

METHODS

Dofetilide, ranolazine, and a combination of these were administered in 4 incremental dosing regimens to horses with acutely pacing-induced AF. Time to cardioversion, atrial effective refractory period, and AF vulnerability and duration were assessed.

RESULTS

Of 8 horses, 6 cardioverted to sinus rhythm after infusion with a combination of 0.889 μg/kg dofetilide and 0.104 mg/kg ranolazine. Two horses cardioverted with 0.104 mg/kg ranolazine alone, and 3 cardioverted with 0.889 μg/kg dofetilide alone. The combination therapy decreased AF vulnerability (P < 0.05) and AF duration (P < 0.05). No change in atrial effective refractory period was detected with any of the drugs.

CONCLUSIONS

The combination of dofetilide and ranolazine showed increased antiarrhythmic effects on acutely induced AF in horses, affecting time to cardioversion, AF vulnerability, and AF duration.

背景

抗心律失常化合物对心房颤动（AF）的疗效往往降低，并且可能显示出心脏和/或非心脏毒性。通过结合具有不同机制的两种化合物可以提高疗效，并且可以使用每种化合物的较低剂量，从而降低不良反应的可能性。本研究的目的是研究如果联合使用，是否可以降低多非利特和雷诺嗪的有效剂量。

方法

在急性起搏诱导 AF 的马中，以 4 种递增剂量方案给予多非利特、雷诺嗪和这些药物的组合。评估电复律时间、心房有效不应期以及 AF 易感性和持续时间。

结果

在 8 匹马中，有 6 匹在输注 0.889μg/kg 多非利特和 0.104mg/kg 雷诺嗪的组合后转为窦性心律。有 2 匹马单独用 0.104mg/kg 雷诺嗪，3 匹马单独用 0.889μg/kg 多非利特转为窦性心律。联合治疗降低了 AF 易感性（P < 0.05）和 AF 持续时间（P < 0.05）。任何药物都未检测到心房有效不应期的变化。