Effects of long‐term oral administration of amiodarone on the electromechanical performance of rabbit ventricular muscle

<jats:p><jats:list list-type="explicit-label"> <jats:list-item><jats:p>The effects of long‐term administration of oral amiodarone on transmembrane action potential and contraction of ventricular muscle were investigated in rabbits.</jats:p></jats:list-item> <jats:list-item><jats:p>ECGs of rabbits that received oral amiodarone 50 mg or 100 mg kg<jats:sup>−1</jats:sup> 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<jats:sup>−1</jats:sup> and 1.47–3.63 μg g<jats:sup>−1</jats:sup> wet wt. respectively.</jats:p></jats:list-item> <jats:list-item><jats:p>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 <jats:inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="graphic/j.1476-5381.1992.tb12774.x.fu1.gif" xlink:title="inline image" /> was also observed at the higher dose. The APD prolongation by chronic amiodarone, unlike acute effects of sotalol, E‐4031, Cs<jats:sup>+</jats:sup> and 4‐aminopyridine, did not show marked reverse use‐dependence.</jats:p></jats:list-item> <jats:list-item><jats:p>APD and <jats:inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="graphic/j.1476-5381.1992.tb12774.x.fu2.gif" xlink:title="inline image" /> restitution following slow basic stimuli (0.03 Hz) were unaffected by chronic treatment with amiodarone.</jats:p></jats:list-item> <jats:list-item><jats:p>Acute application of amiodarone (10 μ<jats:sc>m</jats:sc>) caused a significant decrease in APD and developed tension, as well as a marked use‐dependent <jats:inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="graphic/j.1476-5381.1992.tb12774.x.fu3.gif" xlink:title="inline image" /> inhibition with fast recovery kinetics.</jats:p><jats:p><jats:bold>6</jats:bold> 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.</jats:p></jats:list-item> </jats:list></jats:p>