Original ArticlesAmiodarone: ionic and cellular mechanisms of action of the most promising class III agent
Section snippets
Acute effects of amiodarone
In cardiac cells or tissues whose excitation depends on activation of fast sodium channels, the most consistent change of action potential configuration elicited by acute application of amiodarone is a decrease of the maximum upstroke velocity (Vmax). This Vmax inhibition is enhanced in a frequency- or use-dependent manner like class I antiarrhythmic drugs.24, 25, 26, 27, 28, 29 Onset and offset kinetics of the use-dependent Vmax inhibition are relatively rapid. The recovery time constant (tR)
Chronic effects of amiodarone
The most prominent effect of chronic amiodarone on action potentials of cardiac cells is the prolongation of APD (class III action). This has been confirmed in the working myocardium (atrial and ventricular muscles) as well as in specialized conducting systems (sinoatrial node, atrioventricular nodes, and Purkinje fibers) in a variety of animal species.18 Regarding the class I action of chronic amiodarone, there is a considerable controversy among investigators. Some studies showed
Amiodarone and thyroid hormones
One molecule of amiodarone contains 2 iodine atoms comprising 37% of total molecular weight, and it shares some structural analogies with thyroid hormones.21, 61 Cardiac effects of amiodarone are similar to those seen in hypothyroidism in many aspects22, 61: a prolongation of APD and the refractory period of all cardiac tissues, bradycardia, reduced myocardial oxygen consumption, reduced myocardial β-adrenergic receptor density, prolonged systolic interval, decreased Ca2+-ATPase activity,
Conclusions
This review has pointed out fundamental differences between acute and chronic effects of amiodarone on the electrophysiologic properties of cardiac cells. As an acute effect, amiodarone inhibits both inward and outward currents. The inhibition of inward sodium and calcium currents is enhanced in a use- and voltage-dependent manner, resulting in the suppression of excitability and conductivity in both INa- and ICa-dependent cardiac tissues. The inhibition is greater in the tissues stimulated at
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