Key result
Administration of 10 mg/kg ivabradine in anesthetized mice decreased spontaneous heart rate by ~13% and increased QRS duration by ~18%.
Why the study?
Ivabradine was shown to inhibit voltage-gated Na channels in vitro, which may reduce conduction velocity in cardiac chambers, prompting in vivo evaluation.
Does ivabradine reduce conduction velocity in the AV node and ventricles in anesthetized mice?
Does ivabradine reduce conduction velocity in the AV node and ventricles in anesthetized mice?
Ivabradine prolongs conduction in the AV-node and ventricles in vivo in mice, likely due to inhibition of voltage-gated Na channels.
May slow ventricular conduction in mice beyond HR effects; leaves open Na-channel inhibition and human relevance.
Ivabradine blocks hyperpolarisation-activated cyclic nucleotide-gated (HCN) channels, thereby lowering the heart rate, an action that is used clinically for the treatment of heart failure and angina pectoris. We and others have shown previously that ivabradine, in addition to its HCN channel blocking activity, also inhibits voltage-gated Na channels in vitro at concentrations that may be clinically relevant. Such action may reduce conduction velocity in cardiac atria and ventricles. Here, we explore the effect of administration of ivabradine on parameters of ventricular conduction and repolarization in the surface ECG of anesthetized mice. We found that 5 min after i.p. administration of 10 mg/kg ivabradine spontaneous heart rate had declined by ~13%, which is within the range observed in human clinical studies. At the same time a significant increase in QRS duration by ~18% was observed, suggesting a reduction in ventricular conduction velocity. During transesophageal pacing at heart rates between 100 and 220 beats/min there was no obvious rate-dependence of ivabradine-induced QRS prolongation. On the other hand, ivabradine produced substantial rate-dependent slowing of AV nodal conduction. We conclude that ivabradine prolongs conduction in the AV-node and in the ventricles in vivo.
No takes yet. Share an insight, caveat, or question.
Amstetter et al. (2020) studied this question. Ivabradine was evaluated on Ventricular conduction and repolarization parameters (heart rate and QRS duration). Administration of 10 mg/kg ivabradine in anesthetized mice decreased spontaneous heart rate by ~13% and increased QRS duration by ~18%.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: