Electrophysiologic and antiarrhythmic actions of pirmenol on rabbit and guinea pig cardiac preparations.
The electrophysiological and antiarrhythmic effects of pirmenol HCl were examined using the microelectrode technique applied to multicellular preparations and the suction-pipette whole-cell clamp method applied to ventricular myocytes from rabbit and guinea pig hearts. Pirmenol at 5 microM and higher doses suppressed the sinus node automaticity by depressing the slow diastolic depolarization without changing the maximum diastolic potential. Pirmenol at 1 microM and higher doses depressed the maximum upstroke velocity (Vmax) of action potentials and prolonged the action potential duration at 90% repolarization in atrial muscles and Purkinje fibers without affecting resting membrane potentials. Pirmenol at 5 microM depressed the early part of the plateau and lengthened the final repolarization of the action potentials in ventricular myocytes, of which effects were attributed to the depression of the calcium current and the delayed outward K+ current. Triggered tachyarrhythmias arising from delayed afterdepolarizations in papillary muscles and ventricular myocytes were markedly inhibited by 1-5 microM pirmenol. The drug changed the amplitude and appearance of the transient inward current in ventricular myocytes. These results suggest that pirmenol has electrophysiologic properties that could provide an antiarrhythmic action on various types of arrhythmias.
Sawanobori
T
T
Department of Cardiovascular Diseases, Tokyo Medical and Dental University, Japan.
Adaniya
H
H
Yamashita
K
K
Kawano
S
S
Hayami
H
H
Kuga
K
K
Hiraoka
M
M
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D004594:Electrophysiology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D008839:Microelectrodes; D009206:Myocardium / Q000166:cytology; D010210:Papillary Muscles / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D011690:Purkinje Fibers / Q000502:physiology; D011817:Rabbits; D012849:Sinoatrial Node / Q000502:physiology; D013045:Species Specificity
D000889:Anti-Arrhythmia Agents; D007473:Ion Channels; D010880:Piperidines; D011189:Potassium Chloride; C024318:pirmenol