Comparative hemodynamic effects of amiodarone, sotalol, and d-sotalol.

ABSTRACT

The effects of intravenous boluses of amiodarone (5 mg/kg), racemic sotalol (enantiomeric ratio d/l-sotalol 11;1.5 mg/kg), and d-sotalol (0.75 mg/kg) on mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), total peripheral resistance (TPR), left ventricular end-diastolic pressure (LVEDP), and peak rate of change of left ventricular pressure (LV dp/dt) were assessed in conscious rabbits. Amiodarone and sotalol had a modest negative inotropic effect amiodarone reduced peak LV dp/dt by 8 +/ 2% (mean +/- SEM) (p < 0.05) and sotalol by 6 +/- 2% (p < 0.05). These two drugs had quite different effects on CO as a result of differences in their actions on peripheral blood vessels amiodarone caused a 13 +/- 3% (p < 0.05) increase in CO associated with a substantial vasodilatory effect (TPR reduced 25 +/- 3%; p < 0.01); sotalol did not produce any substantial change in either CO or TPR. Bolus intravenous injection of amiodarone was associated with a significant increase in HR (12 +/- 3%; p < 0.01), whereas sotalol reduced HR by 7 +/- 1% (p < 0.05). In contrast, administration of the dextro-rotatory optical isomer, d-sotalol, produced no significant change in peak LV dp/dt, LVEDP, CO, TPR, or HR. These results confirm that amiodarone and racemic sotalol have a comparatively weak cardiodepressant action. The experiments also show that the reduction in cardiac performance associated with racemic sotalol is mediated predominantly through the beta-adrenoreceptor blocking action of the levo-rotatory isomer (l-sotalol) rather than any substantial cardiodepressant effect of the dextro-rotatory isomer.