RT Journal Article
SR Electronic
T1 Electrophysiologic Effects of Chronic Amiodarone Therapy and Hypothyroidism, Alone and in Combination, on Guinea Pig Ventricular Myocytes
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 156
OP 165
VO 289
IS 1
A1 Ralph F. Bosch
A1 Gui-Rong Li
A1 Rania Gaspo
A1 Stanley Nattel
YR 1999
UL http://jpet.aspetjournals.org/content/289/1/156.abstract
AB 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 andIK1 (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 IKsreduction, similar to hypothyroidism alone; reducedIKr 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. The American Society for Pharmacology and Experimental Therapeutics