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Electrophysiologic effects of amiodarone experimental and clinical observation relative to serum and tissue drug concentrations

, : Electrophysiologic effects of amiodarone experimental and clinical observation relative to serum and tissue drug concentrations. American Heart Journal 108(4 PART 1): 890-898

Oral amiodarone is a potent antiarrhythmic agent with a slow onset of action. Its electrophysiologic properties following chronic administration are well known, but its acute electrophysiological actions are poorly defined. The objectives of the present study were to correlate the electrophysiologic actions of i.v. amiodarone in humans with the acute and chronic effects of the drug relative to plasma and tissue concentrations of the drug. In humans (n = 10), 5 mg/kg i.v. amiodarone (serum concentration 6.50 .+-. 3.34 .mu.g/ml at 10 min, 2.13 .+-. 0.71 .mu.g/ml at 20 min, n = 7) increased the AH interval by 16.4% (P < 0.005), the antegrade effective refractory period (ERP) of the atrioventricular (AV) node by 14.4% (P < 0.025), and the functional refractory period (FRP) of the AV node of 15.5% (P < 0.005%). The ERP or FRP of the atrium of the right ventricle was not significantly changed; there was no effect on the HV interval or the QT and R-R intervals of the ECG. In rabbits (n = 11) given 10 mg/kg i.v. amiodarone (mean .+-. SD serum concentration 0.49 .+-. 0.17 .mu.g/ml; mean myocardial concentration 7.0 .+-. 1.9 .mu.g/gm, n = 3), there were no significant effects on the ECG intervals. In isolated rabbit sinoatrial (SA) node, atria, and AV node (3 preparations) superfused with 5 x 10-6 M amiodarone (3.41 .mu.g/ml), there was no effect on the action potential duration (APD) or other parameters of the transmembrane potential. Rabbits chronically pretreated with amiodarone (20 mg/kg i.p.) for 3 wk had serum drug concentrations of 0.98 .+-. 0.52 .mu.g/ml (n = 4) and myocardial levels of 11.52 .+-. 7.2 .mu.g/gm at 3 wk and 0.50 .+-. 0.18 .mu.g/ml and 14.8 .+-. 6.4 .mu.g/gm, respectively, at 6 wk. Compared to the values in control series, the spontaneous cycle length of the SA node was prolonged by 24% (P < 0.05) at 3 wk and 35.5% (P < 0.01) at 6 wk. The Vmax was affected in none of the tissues but APD was significantly lengthened in all. In atria the APD was increased by 27.6% (P < 0.01) at 3 wk and 32.8% (P < 0.01) at 6 wk; in ventricular muscle the corresponding values were 11.0% (P < 0.05) and 25.3% (P < 0.01). Major differences were indicated between the chronic and acute electrophysiologic effects of amiodarone, difference which are relevant to the interpretation Of the antiarrhythmic actions of the drug following i.v. and oral administration.

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Accession: 005349286

PMID: 6485999

DOI: 10.1016/0002-8703(84)90451-4

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