Effects of phosphodiesterase‐1 inhibitor on pulmonary vein electrophysiology and arrhythmogenesis
| Autor: | Yung Kuo Lin, Dony Yugo, Yao Chang Chen, Shih Ann Chen, Jen Hung Huang, Chih Min Liu, Yi Jen Chen |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Patch-Clamp Techniques
Phosphodiesterase Inhibitors Clinical Biochemistry Diastole Action Potentials 030204 cardiovascular system & hematology Pharmacology Heterocyclic Compounds 4 or More Rings Biochemistry Pulmonary vein 03 medical and health sciences 0302 clinical medicine medicine Animals Myocytes Cardiac 030212 general & internal medicine Beating rate Chemistry Phosphodiesterase Atrial fibrillation General Medicine Cyclic Nucleotide Phosphodiesterases Type 1 medicine.disease Microelectrode Electrophysiology Pulmonary Veins Heart failure Calcium Rabbits |
| Zdroj: | European Journal of Clinical Investigation. 51 |
| ISSN: | 1365-2362 0014-2972 |
| DOI: | 10.1111/eci.13585 |
| Popis: | 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 (INa-Late ), L-type calcium current (ICa-L ) 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 INa-Late , ICa-L and NCX current. Considering its therapeutic potential in heart failure, targeting PDE-1 inhibition may provide a novel strategy for managing atrial arrhythmogenesis. |
| Databáze: | OpenAIRE |
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