Ranolazine Prevents Levosimendan-Induced Atrial Fibrillation
| Autor: | Dirk G. Dechering, Florian Reinke, Michael Fehr, Gerrit Frommeyer, Christian Ellermann, Anja Kohnke, Simon Kochhäuser, Lars Eckardt |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Inotrope medicine.medical_specialty Atrial action potential Acute decompensated heart failure Refractory Period Electrophysiological Ranolazine Action Potentials 03 medical and health sciences Refractory Internal medicine Atrial Fibrillation medicine Animals Drug Interactions Simendan Pharmacology business.industry Hydrazones Atrial fibrillation General Medicine Levosimendan Baseline data medicine.disease Pyridazines 030104 developmental biology Cardiology Rabbits business Anti-Arrhythmia Agents medicine.drug |
| Zdroj: | Pharmacology. 102(3-4) |
| ISSN: | 1423-0313 |
| Popis: | Objectives: Levosimendan is a calcium sensitizer that is used as positive inotropic drug in acute decompensated heart failure. An increased incidence of atrial fibrillation after levosimendan-treatment was observed in clinical and experimental studies. Due to the limited range of antiarrhythmic drugs, the aim of the present study was to assess potential antiarrhythmic effects of ranolazine in levosimendan-pretreated isolated rabbit hearts. Methods: Twelve rabbit hearts were excised and retrogradely perfused employing the Langendorff setup. Left and right atrial catheters were used to record monophasic action potentials and to obtain cycle length-dependent atrial action potential durations (aAPD90) and effective refractory periods (aERP). After obtaining baseline data, 0.5 µmol/L levosimendan was infused. Subsequently, 10 µmol/L ranolazine was administered. Results: Infusion of levosimendan led to a reduction of aAPD90 (–9 ms, p < 0.05) and aERP (–13 ms, p < 0.05). Additional treatment with ranolazine prolonged aAPD90 (+23 ms, p < 0.01) and aERP (+30 ms, p < 0.05). Under baseline conditions, a predefined pacing protocol induced 77 episodes of atrial fibrillation. Infusion of levosimendan enhanced the vulnerability to atrial fibrillation (132 episodes, p = 0.14). Further treatment with ranolazine had a significant antiarrhythmic effect (61 episodes, p < 0.05). Conclusions: In this study, ranolazine seems to prevent atrial fibrillation in levosimendan-pretreated hearts. Underlying mechanism is a prolongation of atrial repolarization and aERP. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|