Electrophysiological effects of a chemical defibrillatory agent, dibenzepin.
OBJECTIVE
The aim was to study the cellular cardiac electrophysiological effects of the antifibrillatory drug, dibenzepin.


METHODS
Standard microelectrode techniques were used to measure the effects of dibenzepin (3 microM, 9 microM) on conduction time, Vmax and input resistance in canine papillary muscles, in vitro, at three paced cycle lengths (1000, 400, 200 ms). Results were compared when adrenaline (0.5-5 microM) or propranolol (0.2 microM) were present.


METHODS
Papillary muscles (n = 25) from hearts of adult mongrel dogs, weight 13-18 kg, were used.


RESULTS
Dibenzepin, at 3 microM, caused significant reduction of Vmax at cycle lengths less than or equal to 400 ms. Paradoxically, the conduction time decreased at all three cycle lengths when measured along the longitudinal axis of the fibre between two microelectrodes spaced 2 mm apart. Superfusion of dibenzepin (3 microM) and propranolol (0.2 microM) significantly reduced Vmax and lengthened conduction time at all cycle lengths. Dibenzepin reduced input resistance from 1.45 to 0.76 M omega, thereby suggesting that improved coupling may occur between cells to account for the shortening of conduction time. Propranolol blocked these results.


CONCLUSIONS
The defibrillatory action of dibenzepin may be related to a decreased intercellular resistance caused by increased catecholamine availability during fibrillation. This would result in improved conduction and, thereby, a decrease of the critical number of asynchronous re-entrant circuits necessary to maintain fibrillation.
Amitzur
G
G
Cardiology Section (111), Veterans Administration Medical Center (State University of New York), Brooklyn 11209.
el-Sherif
N
N
Gough
W B
WB
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents; D003984:Dibenzazepines / Q000494:pharmacology*; D004285:Dogs; D004837:Epinephrine / Q000494:pharmacology; D006329:Heart Conduction System / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D010210:Papillary Muscles / Q000187:drug effects* / Q000502:physiology; D011433:Propranolol / Q000494:pharmacology; D014693:Ventricular Fibrillation / Q000503:physiopathology
D000889:Anti-Arrhythmia Agents; D003984:Dibenzazepines; D011433:Propranolol; D004837:Epinephrine