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Effects of long‐term oral administration of amiodarone on the electromechanical performance of rabbit ventricular muscle
Author(s) -
Kodama Itsuo,
Suzuki Ryoko,
Kamiya Kaichiro,
Iwata Hirokazu,
Toyama Junji
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb12774.x
Subject(s) - amiodarone , repolarization , medicine , qt interval , sotalol , antiarrhythmic agent , oral administration , papillary muscle , cardiology , endocrinology , anesthesia , electrophysiology , atrial fibrillation , heart disease
1 The effects of long‐term administration of oral amiodarone on transmembrane action potential and contraction of ventricular muscle were investigated in rabbits. 2 ECGs of rabbits that received oral amiodarone 50 mg or 100 mg kg −1 daily for 4 weeks, showed a significant prolongation of RR, QT and corrected QT (QTc) intervals, whereas PQ and QRS were unaffected. Serum and myocardial tissue amiodarone concentrations were 0.14–0.18 μg ml −1 and 1.47–3.63 μg g −1 wet wt. respectively. 3 Right ventricular papillary muscles isolated from treated rabbits were characterized by a moderate prolongation of action potential duration (APD) compared with controls. A slight decrease of the maximum upstroke velocity was also observed at the higher dose. The APD prolongation by chronic amiodarone, unlike acute effects of sotalol, E‐4031, Cs + and 4‐aminopyridine, did not show marked reverse use‐dependence. 4 APD and restitution following slow basic stimuli (0.03 Hz) were unaffected by chronic treatment with amiodarone. 5 Acute application of amiodarone (10 μ m ) caused a significant decrease in APD and developed tension, as well as a marked use‐dependent inhibition with fast recovery kinetics. 6 These findings suggest that a major and consistent electro‐physiological effect of chronic amiodarone is repolarization delay (Class‐III action) showing minimal frequency‐dependence. However, when amiodarone above a certain concentration is present in the extracellular space, a fast kinetic Class‐I action would be added as an acute effect.