Age-Dependent Changes in the Effects of Amiodarone on Rabbit Cardiac Myocyte Contractions.
BACKGROUND: Intravenous amiodarone has increasingly been used to control life-threatening atrial and ventricular arrhythmias. In addition to its four antiarrhythmic properties, amiodarone may have complex effects on intracellular Ca(2+) stores and myocyte contractility. METHODS AND RESULTS: Contraction amplitude was recorded for cardiac ventricular myocytes isolated from neonatal and adult rabbits. Sarcoplasmic reticulum (SR) Ca(2+) stores were loaded to steady-state levels by a train of eight electric field stimulations. The SR Ca(2+) load was quantified by recording the contraction amplitude resulting from the complete depletion of SR Ca(2+) 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 Ca(2+) channel blockade with diltiazem. CONCLUSIONS: Amiodarone markedly inhibits caffeine-induced contraction in neonatal myocytes but has no significant effect on adult myocytes. Ca(2+) influx through amiodarone-sensitive Ca(2+) channels may play a primary role in maintaining SR Ca(2+) stores in neonatal heart.
Chen
F
School of Medicine, University of California at Los Angeles, Los Angeles, California, USA
Naim
S
Friedman
WF
Klitzner
TS
Wetzel
GT