Facilitation of epinephrine-induced afterdepolarizations by class III antiarrhythmic drugs.
The electrophysiologic actions of epinephrine (10(-9) M, 10(-8) M, and 10(-7) M) were evaluated in canine Purkinje fibers pretreated with the class III antiarrhythmic drugs clofilium (10(-7) M) or d,l-sotalol (10(-6) M). Clofilium and d,l-sotalol prolonged action potential duration at 50% and 90% of repolarization without provoking early afterdepolarization (EAD) or delayed afterdepolarization (DAD). Subsequent administration of epinephrine provoked both bradycardia-dependent EADs and tachycardia-dependent DADs in clofilium-treated Purkinje fibers, with predominantly EADs observed in d,l-sotalol-treated Purkinje fibers. A temporary increase in Ca0(+2) from 1.35 mM to 5 mM suppressed both EADs and DADs. The data demonstrate facilitation of epinephrine-induced EADs and DADs by class III antiarrhythmic drugs. The acute suppression of both EADs and DADs observed following an acute increase in Ca0(+2) suggests inward Na(+)-Ca0(+2) exchange current as a basis for both EADs and DADs observed in the presence of class III antiarrhythmic drugs and epinephrine.
Patterson
E
E
Department of Pharmacology, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, USA.
Scherlag
B J
BJ
Szabo
B
B
Lazzara
R
R
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000145:classification / Q000494:pharmacology*; D004285:Dogs; D004837:Epinephrine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D011690:Purkinje Fibers / Q000187:drug effects / Q000502:physiology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D013015:Sotalol / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D000644:Quaternary Ammonium Compounds; C022799:clofilium; D013015:Sotalol; D004837:Epinephrine