Age-Dependent Changes in the Effects of Amiodarone on Rabbit Cardiac Myocyte Contractions

Abstract

Background: Intravenous amiodarone has increasingly been used to control life-threaten ing atrial and ventricular arrhythmias. In addition to its four antiarrhythmic properties, amio darone may have complex effects on intracellular Ca ²⁺ stores and myocyte contractility.

Methods and Results: Contraction amplitude was recorded for cardiac ventricular myo cytes isolated from neonatal and adult rabbits. Sarcoplasmic reticulum (SR) Ca²⁺ stores were loaded to steady-state levels by a train of eight electric field stimulations. The SR Ca²⁺ load was quantified by recording the contraction amplitude resulting from the complete depletion of SR Ca²⁺ stores by exposing the cell to a 1-second pulse of 10 mmol/L caffeine. After the cells were exposed to 1 μmol/L amiodarone for 10 minutes, electrically stimulated contraction amplitudes significantly decreased in both adult and neonatal cells. Caffeine- induced cell contraction amplitudes were not affected by amiodarone in adult ventricular myocytes. By contrast, amiodarone markedly inhibited caffeine-induced contractions in neonatal ventricular myocytes. The inhibitory effect of amiodarone on the caffeine-induced contractions was not replicated by Ca²⁺ channel blockade with diltiazem.

Conclusions: Amiodarone markedly inhibits caffeine-induced contraction in neonatal myo cytes but has no significant effect on adult myocytes. Ca²⁺ influx through amiodarone-sensitive Ca²⁺ channels may play a primary role in maintaining SR Ca²⁺ stores in neonatal heart.