Significant cardiac IK1 inhibition and action potential prolongation induced by the combination of sildenafil and Ba2+ at low concentrations

MACHÁČEK, Martin, Olga ŠVECOVÁ and Markéta BÉBAROVÁ. Significant cardiac IK1 inhibition and action potential prolongation induced by the combination of sildenafil and Ba2+ at low concentrations. In European Muscle Conference 2022. 2022.

Basic information

• Original name: Significant cardiac IK1 inhibition and action potential prolongation induced by the combination of sildenafil and Ba2+ at low concentrations
• Authors: MACHÁČEK, Martin, Olga ŠVECOVÁ and Markéta BÉBAROVÁ.
• Edition: European Muscle Conference 2022, 2022.

Other information

• Original language: English
• Type of outcome: Conference abstract
• Country of publisher: Czech Republic
• Confidentiality degree: is not subject to a state or trade secret
• Organization unit: Faculty of Medicine
• Tags: International impact

Abstract

Sildenafil (Viagra), a commonly used vasodilatory drug, may rarely induce atrial or even ventricular fibrillation. Although changes in cardiac IK1 contribute to the pathogenesis of such arrhythmias, the effect of sildenafil on IK1 has not been studied. We investigated IK1 changes induced by various sildenafil concentrations (0.1–100 µM), and further by a combination of sildenafil and Ba2+ (a specific IK1 inhibitor, which is commonly present in human plasma in concentrations up to 1.5 µM). Experiments were performed by the whole-cell patch-clamp technique on enzymatically isolated rat ventricular cardiomyocytes. Sildenafil and Ba2+ separately caused a significant, reversible, and concentration-dependent inhibition of both inward and outward IK1 components. The combined application of sildenafil and Ba2+ (both at a very low, subclinical concentration of 0.1 µM) elicited a massive potentiation of the aforementioned effect that resulted in a significant prolongation of action potential duration (APD). To our knowledge, similar potentiation of the drug-channel interaction has never been described. The observed massive IK1 inhibition and APD prolongation induced by a combination of 0.1 µM sildenafil and Ba2+ might contribute to the genesis of sildenafil-induced arrhythmias that were rarely observed in patients treated with sildenafil.

Links

• MUNI/A/1133/2021, interní kód MU: Name: Od buňky k medicíně (Acronym: CELLVIEW)

Investor: Masaryk University