Electrophysiologic effects of ketanserin on canine Purkinje fibers, ventricular myocardium and the intact heart.
We studied the actions of ketanserin (KT) on transmembrane action potentials (AP) of canine Purkinje fibers (PF) and ventricular muscle (VM) and on rhythm in vivo. PF AP duration (APD) was increased by KT (10(-8) to 10(-6) M) and shortened at 10(-5) M. KT effect on APD was greater during stimulation at longer cycle lengths and KT induced early afterdepolarizations in two of six PF at [K+]0 = 2.7 mM. Maximum diastolic potential, AP amplitude and Vmax were not changed by KT. In VM, KT (10(-8) to 10(-6) M) prolonged APD; but 10(-5) M KT did not shorten APD, reducing the difference in APD between VM and PF. KT had no effect on slow response Vmax or amplitude but prolonged APD. To analyze whether changes in Na plateau current or transient outward current contributed to KT effects on APD, we used tetrodotoxin (TTX) and 4-aminopyridine. TTX shortened APD and in its presence, KT (10(-5) M) induced no further shortening. In contrast, the effect of KT persisted in the presence of 4-aminopyridine. In six anesthetized, open chest dogs, KT prolonged the QT interval, but did not modify QRS duration and epicardial conduction time or induce arrhythmias. KT facilitated the onset of torsades de pointes during epicardial aconitine application.(ABSTRACT TRUNCATED AT 250 WORDS)
Zaza
A
A
Department of Pharmacology, Columbia University College of Physicians & Surgeons, New York, New York.
Malfatto
G
G
Rosen
M R
MR
D000200:Action Potentials / Q000187:drug effects; D000632:Aminopyrine / Q000494:pharmacology; D000818:Animals; D003971:Diastole / Q000187:drug effects; D004285:Dogs; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006329:Heart Conduction System / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology; D011690:Purkinje Fibers / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D016276:Ventricular Function
D000632:Aminopyrine; D013779:Tetrodotoxin; D007650:Ketanserin; D011188:Potassium