Simple in vitro method to characterize antiarrhythmic agents.
A simple, nonmicroelectrode method was developed for the in vitro identification and characterization of potential antiarrhythmic agents. To evaluate the method, standard antiarrhythmic agents from three different classifications (I, III, IV) were tested in isolated right ventricular guinea pig papillary muscles for their effect on developed tension (DT), excitability (EX), and effective refractory period (ERP). ERP was measured with the use of paired field stimuli. Depression or reversal of the force frequency relationship was an index of an agent's effect on DT. A shift in the stimulus strength-duration relationship was an index of an agent's effect on EX. A computer program was developed for data handling and analysis. Disopyramide phosphate (D, 3.0 x 10(-5) M), sotalol (S, 3.0 x 10(-5) M), clofilium phosphate (C, 1.0 x 10(-5) M), and N-acetyl procainamide hydrochloride (N, 3.0 x 10(-5) M) significantly prolonged ERP (+20, +35, +24, +16 ms, respectively), while verapamil (V, 3.0 x 10(-7) M) and the distilled water vehicle (W) did not. D and V significantly decreased DT (-78% and -57% at 1 Hz, respectively) while W, S, C, and N did not. Only D decreased EX. These data correspond well with findings in other models reported in the literature, supporting the use of this simple in vitro method for identification and characterization of potential antiarrhythmic agents.
Department of Cardiovascular Research, G. D. Searle and Co., Skokie, Illinois.
A M
AM
Hackett
S J
SJ
McDonald
P
P
Schneider
F
F
Schweingruber
S M
SM
Garthwaite
D000120:Acecainide / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004206:Disopyramide / Q000494:pharmacology; D004558:Electric Stimulation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D013015:Sotalol / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D000644:Quaternary Ammonium Compounds; C022799:clofilium; D000120:Acecainide; D013015:Sotalol; D014700:Verapamil; D004206:Disopyramide