Cellular and ionic mechanisms underlying the effects of cilostazol, milrinone, and isoproterenol to suppress arrhythmogenesis in an experimental model of early repolarization syndrome

Heart Rhythm : the Official Journal of the Heart Rhythm Society
Bence PatocskaiCharles Antzelevitch

Abstract

Early repolarization syndrome (ERS) is associated with polymorphic ventricular tachycardia (PVT) and ventricular fibrillation, leading to sudden cardiac death. The present study tests the hypothesis that the transient outward potassium current (Ito)-blocking effect of phosphodiesterase-3 (PDE-3) inhibitors plays a role in reversing repolarization heterogeneities responsible for arrhythmogenesis in experimental models of ERS. Transmembrane action potentials (APs) were simultaneously recorded from epicardial and endocardial regions of coronary-perfused canine left ventricular (LV) wedge preparations, together with a transmural pseudo-electrocardiogram. The Ito agonist NS5806 (7-15 μM) and L-type calcium current (ICa) blocker verapamil (2-3 μM) were used to induce an early repolarization pattern and PVT. After stable induction of arrhythmogenesis, the PDE-3 inhibitors cilostazol and milrinone or isoproterenol were added to the coronary perfusate. All were effective in restoring the AP dome in the LV epicardium, thus abolishing the repolarization defects responsible for phase 2 reentry and PVT. Arrhythmic activity was suppressed in 7 of 8 preparations by cilostazol (10 μM), 6 of 7 by milrinone (2.5 μM), and 7 of 8 by isoproterenol ...Continue Reading

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Citations

May 3, 2016·Indian Pacing and Electrophysiology Journal·Soumya R Mahapatra, Praloy Chakraborty
Aug 31, 2018·Journal of Cellular and Molecular Medicine·Hao YaoSu-Hua Wu
Feb 1, 2018·Journal of the Endocrine Society·Shigehiro KarashimaTakashi Yoneda
Jul 26, 2016·Frontiers in Physiology·Ben N MercerSaagar Mahida
Dec 14, 2018·Frontiers in Cardiovascular Medicine·Felix BourierMélèze Hocini
Oct 26, 2018·Circulation. Arrhythmia and Electrophysiology·Namsik YoonCharles Antzelevitch
Jul 14, 2021·Trends in Cardiovascular Medicine·Charles Antzelevitch, Jose M Di Diego

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