Dronedarone's Inhibition of If Current Is the Primary Mechanism Responsible for Its Bradycardic Effect

Dronedarone's Bradycardic Effect Introduction The mechanism(s) whereby dronedarone reduces sinus rate are not well understood, although L‐type calcium channel antagonism, beta‐adrenergic blockade, and inhibition of If are plausible. Methods and Results In anesthetized pigs, we compared the effects of dronedarone to the prototypical If inhibitor, ivabradine, and the L‐type calcium channel antagonist diltiazem on heart rate, mean arterial blood pressure (MAP), and contractility. Dronedarone's effects on the phenylephrine‐induced rise in MAP and on the chronotropic response to isoproterenol were also investigated. Cumulative doses of dronedarone (0.5 mg/kg, i.v., and 5.0 mg/kg, i.v.; plasma level: 80 ± 16.1 nM) progressively reduced heart rate (P