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Amiodarone, a molecule initially developed as an antianginal agent, is considered to be the most powerful antiarrhythmic drug. It prolongs ventricular repolarisation and the refractory periods of all cardiac fibres uniformly, and, at high doses, blocks the transmembrane sodium influx. Amiodarone exerts a non competitive alpha and beta adrenolytic effect and interferes with the metabolism of the thyroid hormones. Its accumulation is slow and excretion progressive. The main metabolite (desethylamiodarone) also has electrophysiological properties and contributes to the antiarrhythmic effect. The efficacy of amiodarone in cardiac arrhythmias is limited in chronic administration by the possibility of dose-dependent secondary effects.

The electrophysiological effects of cibenzoline on the myocardium of the anesthetized dog were studied by the endocavitary catheter method. Plasma cibenzoline levels were measured throughout. The cibenzoline effects on the sinus rate were negligible. The corrected sinus recovery time was significantly prolonged only following chronic oral administration. Atrial refractory periods were significantly increased only at the fifth minute following acute intravenous administration and after chronic oral treatment. The intranodal conduction time (AH) and the refractory periods in atrio-ventricular node were slightly modified or not at all. On the other hand, intraventricular and His-Purkinje (HV) conduction times, ventricular refractory periods and QRS duration were strongly increased following acute or chronic administration. This would imply a principal effect on the rapid kinetics sodium entry current. Nevertheless, the very marked effect upon this current could, under the experimental conditions adopted, have masked a lesser action upon other membrane permeabilities, involved in other myocardial structures.

Electrophysiological effects of butoprozine (L 9394 Labaz) were investigated on the anaesthetized dog by programmed electrical stimulation of the heart and simultaneous recording of the His bundle electrogram and monophasic action potentials from the auricular and ventricular endocardial wall. Butoprozine injected intravenously depressed sino-atrial node function, lengthened A-V nodal conduction time and the A-V nodal refractory period, and prolonged the atrial refractory period. Thus butoprozine acted preferentially on parts of the myocardial tissue where the slow inward current seems to be particularly involved. In this respect, butoprozine was more active than amiodarone, but in contrast to this drug, butoprozine did neither prolong the ventricular monophasic action potential duration nor the ventricular refractory period. In the anaesthetized dog both drugs have practically analogous actions except at the ventricular level, which suggests that their effect on ionic currents at this level may be different.

A study was performed to assess whether plasma and myocardial concentrations of amiodarone correlated with changes on the surface electrocardiogram. Nine patients--seven with angina and two with paroxysmal ventricular tachycardia--were treated with oral amiodarone (200-400 mg daily) for at least nine months before undergoing cardiac surgery. QT intervals were measured from lead II of the surface electrocardiograms recorded before amiodarone treatment and immediately before surgery. Patients with prominent U waves after taking amiodarone were excluded from the study. Plasma and myocardial samples were collected at the beginning of the surgical procedure for estimating plasma and myocardial concentrations using the high performance liquid chromatographic technique. Amiodarone caused a significant lengthening of the QTc interval. There was a good correlation between plasma and myocardial concentrations, and both correlated well with the percentage increase in the QTc interval. Although there was a strong correlation between the dosage given (mg/kg/day) and both plasma and myocardial concentrations, the correlation with the percentage increase in the QTc interval was weaker but still highly significant. Despite previous reports to the contrary, the findings indicate that the plasma concentration of amiodarone does correlate well with the myocardial concentration. The degree of lengthening of the QTc interval may be used clinically to estimate the myocardial concentration of amiodarone.

The dependence of T-wave alternans on diastolic resting period duration as well as on regional differences in monophasic action potential duration was studied in the in situ dog heart. T-wave alternans was elicited when diastolic resting period shortened to values less than 41 +/- 6% of the cardiac cycle. This could be attained either by increasing the driving rate, or lengthening action potential duration by inducing hypocalcemia. During T-wave alternans, monophasic action potentials recorded from anterior and posterior left ventricular surface showed an alternation in duration; the degree in alternation in both regions differed and related to T-wave polarity.