AI Article Synopsis
- PDE-1 isoform inhibitors, specifically ITI-214, show promise for treating heart failure by affecting the heart's electrical activity, particularly in the pulmonary vein (PV), which often triggers atrial fibrillation.
- Using techniques like microelectrodes and patch clamps, the study assessed how ITI-214 impacts PV electrical function, revealing significant reductions in PV spontaneous beating rate and diastolic tension at higher concentrations.
- The results indicate that ITI-214 decreases specific ionic currents (late sodium current, L-type calcium current, and reverse sodium-calcium exchanger), suggesting that PDE-1 inhibition could be a novel therapeutic approach for managing atrial fibrillation and heart failure.
Article Abstract
Introduction: Phosphodiesterase (PDE) isoform inhibitors have mechanical and electrical effects on the heart. Inhibition of PDE-1 enzymes is a novel strategy for treating heart failure. However, the electrophysiological effects of PDE-1 inhibition on the heart remain unclear. This study explored the effects of PDE-1 inhibition using ITI-214 on electrical activity in the pulmonary vein (PV), the most common trigger of atrial fibrillation, and investigated the underlying ionic mechanisms.
Methods: Conventional microelectrodes or whole-cell patch clamps were employed to study the effects of ITI-214 (0.1-10 μM) on PV electrical activity, mechanical responses and ionic currents in isolated rabbit PV tissue specimens and isolated single PV cardiomyocytes.
Results: ITI-214 at 1 μM and 10 μM (but not 0.1 μM) significantly reduced PV spontaneous beating rate (10 ± 2% and 10 ± 3%, respectively) and PV diastolic tension (11 ± 3% and 17 ± 3%, respectively). ITI-24 (1 μM) significantly reduced late sodium current (I ), L-type calcium current (I ) and the reverse mode of the sodium-calcium exchanger (NCX), but it did not affect peak sodium currents.
Conclusions: ITI-214 reduces PV spontaneous activity and PV diastolic tension by reducing I , I and NCX current. Considering its therapeutic potential in heart failure, targeting PDE-1 inhibition may provide a novel strategy for managing atrial arrhythmogenesis.
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| http://dx.doi.org/10.1111/eci.13585 | DOI Listing |
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