Actions of flecainide on susceptibility to phase-2 ventricular arrhythmias during infarct evolution in rat isolated perfused hearts
| Autor: | Gajen Kanaganayagam, Ruchi Kabra, Hugh Clements-Jewery, Michael J. Curtis |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Pharmacology
Tachycardia Fibrillation medicine.medical_specialty business.industry medicine.medical_treatment Antiarrhythmic agent medicine.disease QT interval Coronary occlusion Internal medicine Anesthesia Ventricular fibrillation cardiovascular system medicine Cardiology cardiovascular diseases Myocardial infarction medicine.symptom business Flecainide medicine.drug |
| Zdroj: | British Journal of Pharmacology. 147:468-475 |
| ISSN: | 0007-1188 |
| DOI: | 10.1038/sj.bjp.0706633 |
| Popis: | The mechanism of flecainide-induced unexpected death remains uncertain. Phase-2 ventricular arrhythmias occur during infarct evolution. We examined whether flecainide (0.74 and 1.48 microM, representing the peak unbound plasma and total blood concentrations, respectively, at 'therapeutic' dosage) has proarrhythmic activity on phase-2 arrhythmia susceptibility during infarct evolution. To achieve this, we used the Langendorff-perfused rat heart preparation (n=8 per group) in which baseline phase-2 arrhythmia susceptibility is low. Left main coronary occlusion evoked phase-1 (acute ischaemia-induced) ventricular arrhythmias including fibrillation (VF) in all hearts. By 90 min, hearts were relatively arrhythmia-free. Randomized and blinded switch of perfusion to flecainide at 90 min caused no increase over baseline in the incidence of VF, tachycardia (VT) or premature beats (VPB) during the following 150 min of ischaemia, or during reperfusion (begun 240 min after the onset of ischaemia). In separate hearts, catecholamines (313 nM norepinephrine and 75 nM epinephrine) were co-perfused with flecainide from 90 min of ischaemia. Catecholamine perfusion increased heart rate, coronary flow and QT interval, and shortened PR interval (all P |
| Databáze: | OpenAIRE |
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