Key result
Sildenafil suppresses dofetilide-induced ventricular arrhythmias and abolishes cellular Ca2+ waves by reducing SR Ca2+ content.
Why the study?
PDE5 inhibition reduces ventricular arrhythmias after myocardial ischemia, but the underlying antiarrhythmic mechanisms and the role of intracellular calcium cycling remain unknown.
Population
Dofetilide-induced proarrhythmic sheep model and isolated ventricular myocytes
Comparison
PDE5 inhibition with sildenafil vs control with or without PKG inhibition
Design
Preclinical animal and cellular experimental study
Authors
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Should not yet change clinical arrhythmia management; leaves open PDE5 inhibition for triggered ventricular arrhythmias in patients.
PDE5 inhibition acutely suppresses triggered ventricular arrhythmias in a proarrhythmic large animal model by reducing SR Ca2+ content and suppressing cellular Ca2+ waves via a PKG-dependent mechanism.
Hutchings et al. (2021) studied Ventricular arrhythmias. PDE5 inhibition (sildenafil) was evaluated on Arrhythmia burden, beat-to-beat variability of repolarization, and cellular Ca2+ waves. Acute PDE5 inhibition with sildenafil suppressed dofetilide-induced ventricular arrhythmias in vivo and abolished cellular Ca2+ waves in 12 of 22 cells by reducing SR Ca2+ content.
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