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Journal of Cardiovascular Pharmacology and Therapeutics
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Age-Dependent Changes in the Effects of Amiodarone on Rabbit Cardiac Myocyte Contractions

Fuhua Chen

University of California at Los Angeles, School of Medicine, Los Angeles, California

Suhaila Naim

University of California at Los Angeles, School of Medicine, Los Angeles, California

William F. Friedman

University of California at Los Angeles, School of Medicine, Los Angeles, California

Thomas S. Klitzner

University of California at Los Angeles, School of Medicine, Los Angeles, California

Glenn T. Wetzel

University of California at Los Angeles, School of Medicine, Los Angeles, California

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.

Key Words: antiarrhythmic agent • amiodarone • arrhythmia • neonatal heart • excitation- contraction coupling • Ca2+ channel blocker.

Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 4, No. 1, 23-32 (1999)
DOI: 10.1177/107424849900400105


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