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Vol. 289, Issue 1, 156-165, April 1999

Electrophysiologic Effects of Chronic Amiodarone Therapy and Hypothyroidism, Alone and in Combination, on Guinea Pig Ventricular Myocytes1

Ralph F. Bosch, Gui-Rong Li , Rania Gaspo and Stanley Nattel

Department of Cardiology, University of Tübingen, Tübingen, Germany (R.F.B); Department of Medicine and Research Center, Montreal Heart Institute (G.R.L., R.G., S.N.), and University of Montreal (G.R.L., S.N.), Montreal, Quebec, Canada; and Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada (S.N.)

Amiodarone is a widely used antiarrhythmic drug, the mechanisms of action of which remain incompletely understood. Indirect evidence suggests that the class III properties of amiodarone may be mediated by cardiac antithyroid effects. We sought to determine whether the effects of chronic amiodarone on repolarization in guinea pig hearts can be attributed to an antithyroid action by studying the changes in dofetilide-sensitive rapid (IKr) and dofetilide-resistant slow (IKs) delayed rectifier currents, inward rectifier K+ current (IK1), and action potentials of ventricular myocytes from five groups of guinea pigs: control, hypothyroid, amiodarone-treated for 7 days, hypothyroid plus amiodarone, and vehicle (dimethyl sulfoxide) treated. IKs was reduced by amiodarone (to 61% of control, P < .05, at 50 mV) but was more strongly reduced by hypothyroidism (to 35% of control, P < .01, 50 mV). Amiodarone significantly reduced IKr and IK1 (by 55 and 64% at 10 mV and -50 mV, respectively), which were unaffected by hypothyroidism. Amiodarone alone and hypothyroidism alone had similar action potential-prolonging actions. Hypothyroid animals treated with amiodarone showed a combination of ionic effects (strong IKs reduction, similar to hypothyroidism alone; reduced IKr and IK1, similar to amiodarone alone), along with action potential prolongation significantly greater than that caused by either intervention alone. We conclude that chronic amiodarone and hypothyroidism have different effects on ionic currents and that their combination prolongs action potential duration to a greater extent than either alone in guinea pig hearts, suggesting that the class III actions of amiodarone are not mediated by a cardiac hypothyroid state.

0022-3565/99/2891-0156$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 1999 by The American Society for Pharmacology and Experimental Therapeutics


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