The effects of intravenous boluses of amiodarone (5 mg/kg), racemic so
talol (enantiomeric ratio d/l-sotalol 1:1;1.5 mg/kg), and d-sotalol (0
.75 mg/kg) on mean arterial pressure (MAP), heart rate (HR), cardiac o
utput (CO), total peripheral resistance (TPR), left ventricular end-di
astolic 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 pe
ak 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: a
miodarone 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. Bo
lus intravenous injection of amiodarone was associated with a signific
ant increase in HR (12 +/- 3%; p < 0.01), whereas sotalol reduced HR b
y 7 +/- 1 % (p < 0.05). In contrast, administration of the dextro-rota
tory optical isomer, d-sotalol, produced no significant change in peak
LV dp/dt, LVEDP, CO, TPR, or HR. These results confirm that amiodaron
e and racemic sotalol have a comparatively weak cardiodepressant actio
n. 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 (1-so
talol) rather than any substantial cardiodepressant effect of the dext
ro-rotatory isomer.