Electrophysiological profile of the antiarrhythmic compound asocainol studied on perfused guinea-pig hearts and on isolated cardiac preparations.
The studies deal with electrophysiological effects of asocainol [(+/-)-6,7,8,9-tetrahydro-2,12-dimethoxy-7-methyl-6-phenetyl-5 H-dibenz(d,f)azonine-1-ol] on isolated perfused guinea-pig hearts (Langendorff-preparation), on right ventricular papillary muscles, on Purkinje fibres from the guinea pig, and on isolated sinus nodes from the rabbit. In the perfused heart (n = 5) the lowest effective concentration of asocainol is about 0.2 mumol/l. At a concentration of 2 mumol/l the cardiac electrogram shows in spontaneously beating hearts a mean decrease in frequency of 15%, in electrically driven hearts (150/min at 32 degrees C) prolongation of PQ (+31%), of QRS (+24%) and of QT (+5%). In papillary muscles (32 degrees C; K+e 5.9 mmol/l; stimulation rate 0.5 Hz) asocainol (3-30 mumol/l) exerts the following effects: no change of the resting potential, concentration-dependent reduction of the maximum rate of rise (Vmax) of the action potential (AP) (-16 to -67%) as well as of the AP-amplitude (-4 to -16%), and shortening of the AP-duration at 50% repolarisation (-18 to -43%). The steady-state dependence of Vmax on the resting potential (RP) determined by variation of K+e (5.9-15 mmol/l) is shifted by asocainol to more negative potentials. The percentage deviation from controls of the Vmax-RP relationship is more pronounced at lower membrane potentials. The influence of asocainol on the recovery from inactivation of Vmax shows marked time-dependence. Slow response (Ca2+-mediated) APs elicited by strong stimuli in a K+e-rich solution (K+e 20-24 mmol/l) respond to asocainol (3-10 mumol/l) with a marked reduction in amplitude, Vmax and duration.(ABSTRACT TRUNCATED AT 250 WORDS)
D000200:Action Potentials / Q000187:drug effects; D000779:Anesthetics, Local; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001392:Azocines / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D004562:Electrocardiography; D004594:Electrophysiology; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D010210:Papillary Muscles / Q000187:drug effects; D011690:Purkinje Fibers / Q000187:drug effects; D012849:Sinoatrial Node / Q000502:physiology; D013997:Time Factors
D000779:Anesthetics, Local; D000889:Anti-Arrhythmia Agents; D001392:Azocines; C042287:asocainol; D002118:Calcium