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Chronotropic effects of milrinone in a guinea pig ex vivo model: a pilot study to screen for new mechanisms of action.

J Cardiovasc Pharmacol

January 2025

Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

Positive inotropic responses upon administration of milrinone, an inhibitor of the phosphodiesterase enzyme (PDE), involve a well-pronounced positive chronotropic effect. Here we tested whether milrinone evokes this chronotropic response solely by PDE inhibition or by a concerted action that involve additional pharmacological targets. Milrinone stimulated increases in heart rate were studied in right atrial preparations of guinea pig in the presence or absence of inhibitors of putative ancillary molecular pathways or ion channels: i.

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Background: Brugada syndrome (BrS) is a genetic heart disease that predisposes individuals to ventricular arrhythmias and sudden cardiac death. Although implantable cardioverter-defibrillators (ICDs) and quinidine are primary treatments, recurrent BrS-triggered ventricular arrhythmias can persist. In this setting, epicardial substrate ablation has emerged as a promising alternative for symptomatic patients.

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Background: The ionic mechanism underlying Brugada syndrome (BrS) arises from an imbalance in transient outward current flow between the epicardium and endocardium. Previous studies report that artemisinin, originally derived from a Chinese herb for antimalarial use, inhibits the Ito current in canines. In a prior study, we showed the antiarrhythmic effects of artemisinin in BrS wedge preparation models.

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