Abstract
1. Standard microelectrode methods have been used to record action potentials from guinea-pig ventricular myocardium and dog Purkinje fibres, and to study the effects of the two major metabolites of encainide, O-desmethyl encainide (ODE) and 3-methoxy-O-desmethyl encainide (MODE). 2. In concentrations similar to those found in patients during chronic encainide therapy, neither ODE nor MODE produced significant depression of maximum rate of depolarization (Vmax) of action potentials in unstimulated tissue. Repetitive stimulation, however, was associated with depression of Vmax which increased with increasing driving rates (rate-dependent block, RDB). At the fastest rate studied (interstimulus interval = 300 ms) ODE 1 microM depressed Vmax by 47.5 +/- 5.7% and MODE 1 microM, reduced Vmax by 52.2 +/- 12%. 3. The onset and offset kinetics of this rate-dependent block were very slow. Full development of RDB during a train required over 100 action potentials and the time constants of recovery of Vmax from RDB were 86.4 +/- 37 s for ODE and 100.4 +/- 18 s for MODE. The amount of RDB and its rate of onset increased with drug concentration. The recovery time constants were independent of inter-stimulus interval or drug concentration. Bo...Continue Reading
References
May 1, 1979·Journal of Cardiovascular Pharmacology·R Y Man, P E Dresel
Mar 1, 1979·Biophysical Journal·M Walton, H A Fozzard
Apr 23, 1979·Life Sciences·K R Courtney
Nov 15, 1978·European Journal of Pharmacology·J K GibsonA L Bassett
Jul 1, 1985·The American Journal of Cardiology·D C Harrison
Mar 1, 1987·Journal of Molecular and Cellular Cardiology·K R Courtney
Jun 1, 1985·Journal of the American College of Cardiology·J F CaronJ P Lekieffre
Apr 1, 1986·The American Journal of Cardiology·J MorganrothD M Clark
Feb 1, 1988·Circulation·J T BarbeyD M Roden
Mar 1, 1988·Cardiovascular Research·R T Pallandi, T J Campbell
Jan 15, 1988·The American Journal of Cardiology·D P Zipes
Mar 1, 1987·British Journal of Pharmacology·T J Campbell
Jan 1, 1985·Drugs·P J Podrid
Jun 1, 1985·Circulation Research·D M Roden, B F Hoffman
Feb 15, 1981·Experientia·H Sada, T Ban
Mar 1, 1983·Journal of Cardiovascular Pharmacology·T J Campbell
Feb 1, 1984·The Journal of Clinical Investigation·E L CareyR L Woosley
Sep 1, 1983·British Journal of Pharmacology·T J Campbell
Apr 17, 1980·The New England Journal of Medicine·D M RodenR L Woosley
Dec 1, 1980·American Heart Journal·D C HarrisonJ Mason
Nov 1, 1981·American Heart Journal·R A WinkleD Ross
Apr 1, 1982·Clinical Pharmacology and Therapeutics·R E KatesR A Winkle
Jun 1, 1982·Circulation·R DiBiancoB Sauerbrunn
Jun 1, 1983·Cardiovascular Research·T J Campbell