Comparative effects of tetrodotoxin, lidocaine, and amiodarone on Vmax in guinea pig cardiac Purkinje and papillary muscle fibers.
1. Electrophysiological effects of three drugs (tetrodotoxin, lidocaine, and amiodarone), which are known to depress Na channels in cardiac tissues, were studied on isolated guinea pig Purkinje fibers, by means of microelectrode techniques, and compared the findings with their effects on the ventricular papillary muscle. 2. Special attention was paid with regard to their effects on the maximum upstroke velocity (Vmax) of action potentials. 3. In Purkinje fibers, tetrodotoxin was the most inhibitory for Vmax, then in descending order, amiodarone, and lidocaine. 4. That is, half maximal inhibition (IC50) of Vmax by tetrodotoxin, lidocaine and amiodarone was approximately 1.7 x 10(-5) M, 1.5 x 10(-4) M and 2.8 x 10(-4) M, respectively. 5. As for papillary muscle, higher concentrations of the three drugs were needed to get similar potency. 6. The relationships between the depression in the Vmax and action potential duration are discussed in conjunction with their antiarrhythmic activities.
Aomine
M
M
Department of Medicine, Division of Cardiology, Reingold ECG Center, Northwestern University Medical School, Chicago, IL 60611.
D000200:Action Potentials / Q000187:drug effects; D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D004558:Electric Stimulation; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D007700:Kinetics; D008012:Lidocaine / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D011690:Purkinje Fibers / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology*
D013779:Tetrodotoxin; D008012:Lidocaine; D000638:Amiodarone