Dextrorotatory isomer of sotalol: electrophysiologic effects and interaction with verapamil.
The dextrorotatory isomer of sotalol (d-sotalol) has class III antiarrhythmic properties with known action potential duration (APD) prolonging effects, and is largely devoid of beta-adrenergic blocking activity. We studied its electrophysiologic effects and the mechanism of its APD prolonging effects in sheep Purkinje fibers by means of standard microelectrode techniques. At all concentrations (10(-6) to 10(-4) mol/L), d-sotalol had no effect on Vmax. At 10(-6) mol/L, d-sotalol had no effect on APD. A concentration-dependent effect of 10(-5) to 10(-4) mol/L d-sotalol was found on APD. At peak effect, APD was prolonged by 56% and 49% at 50% (APD50) and 90% (APD90) of repolarization (p less than 0.01). Early afterdepolarizations (EADs) were noted at high concentration of d-sotalol (10(-4) mol/L). These EADs were increased in number by epinephrine. To assess the mechanism of APD prolongation, verapamil (2.0 X 10(-6) mol/L) was added before and after d-sotalol treatment. In the presence of verapamil, no APD prolongation was observed even at the highest d-sotalol concentration (10(-4) mol/L). Next, during APD prolongation at the highest d-sotalol concentration, we added verapamil, noticing a remarkable shortening of APD. In addition, d-sotalol-induced EADs disappeared with addition of verapamil. Thus (1) verapamil blocks d-sotalol-induced APD prolongation and EADs and (2) this may be consistent with a mechanism via slow inward current.
Hiromasa
S
S
Cardiovascular Division, University of Louisville, School of Medicine, KY 40202.
Coto
H
H
Li
Z Y
ZY
Maldonado
C
C
Kupersmith
J
J
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology; D012756:Sheep; D013015:Sotalol / Q000494:pharmacology*; D013237:Stereoisomerism; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology*
D013015:Sotalol; D014700:Verapamil