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Effects of tedisamil (KC‐8857) on cardiac electrophysiology and ventricular fibrillation in the rabbit isolated heart
Author(s) -
Chi Liguo,
Park James L.,
Friedrichs Gregory S.,
Banglawala Yasmin A.,
Perez Maria A.,
Tanhehco Elaine J.,
Lucchesi Benedict R.
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb16724.x
Subject(s) - medicine , ventricular fibrillation , pinacidil , cardiology , electrophysiology , cardiac transient outward potassium current , endocrinology , glibenclamide , patch clamp , diabetes mellitus
1 The direct cardiac electrophysiological and antifibrillatory actions of tedisamil (KC‐8857) were studied in rabbit isolated hearts. 2 Tedisamil (1, 3, and 10 μ m ), prolonged the ventricular effective refractory period (VRP) from 120±18ms (baseline) to 155±19, 171±20, and 205±14 ms, respectively. Three groups of isolated hearts ( n = 6 each) were used to test the antifibrillatory action of tedisamil. Hearts were perfused with 1.25 μ m pinacidil, a K ATP channel activator. Hearts were subjected to hypoxia for 12 min followed by 40 min of reoxygenation. Ventricular fibrillation (VF) developed during hypoxia and reoxygenation in both the control and 1 μ m tedisamil‐treated groups (5/6 and 4/6, respectively). Tedisamil (3 μ m ) reduced the incidence of VF (0/6, P = 0.007 vs . control). 3 In a separate group of hearts, VF was initiated by electrical stimulation. The administration of 0.3 ml of 10 m M tedisamil, via the aortic cannula, terminated VF in all hearts, converting them to normal sinus rhythm. 4 Tedisamil (3 μ m ) reversed pinacidil‐induced negative inotropic effects in rabbit isolated atrial muscle which were equilibrated under normoxia, as well as in atrial muscle subjected to hypoxia and reoxygenation. 5 The results demonstrate a direct antifibrillatory action of tedisamil in vitro . The mechanism responsible for the observed effects may involve modulation by tedisamil of the cardiac ATP‐regulated potassium channel, in addition to its antagonism of I K and I to .