Introduction: Vaughan Williams classification was recently updated to include new antiarrhythmic mechanisms, in which class Id action is defined as Nav1.5 late current inhibition. We characterized in vivo cardiac safety pharmacological profile of typical Id drug ranolazine, which can also inhibit hERG current.
Methods: Ranolazine dihydrochloride in subclinical and clinically relevant doses, 0.3 and 3 mg/kg respectively, was i.v. infused over 10 min to the halothane-anesthetized dogs (n=5).
Results: The subclinical dose increased the heart rate, cardiac output and atrioventricular conduction velocity. Meanwhile, the clinically relevant dose decreased the heart rate, ventricular contraction and mean blood pressure, which resulted in indirectly increasing the total peripheral vascular resistance. Also, it delayed the intra-ventricular conduction and ventricular late repolarization without significantly altering the intra-atrial conduction, ventricular early repolarization or post-repolarization refractoriness (PRR). Moreover, it prolonged the atrial and ventricular effective refractory periods.
Conclusions: The clinically relevant dose of ranolazine did not alter the ventricular early repolarization or PRR in vivo, indicating the class Id action could attenuate hERG current-inhibition associated torsadogenic potential.