DIGOXIN-INDUCED DELAYED AFTERDEPOLARIZATIONS - BIPHASIC EFFECTS OF DIGOXIN ON ACTION-POTENTIAL DURATION AND THE Q-T INTERVAL IN CARDIAC PURKINJE-FIBERS

Few reports exist of digoxin-induced delayed afterdepolarizations (DAD s) and triggered activity recorded in cardiac fibers, and the electrop hysiological characteristics of digoxin-induced DADs and triggered act ivity have not been reported in detail. We studied the electrophysiolo gical properties of digoxin-induced DADs and triggered activity is she ep cardiac Purkinje fibers. Transmembrane voltage was recorded using c onventional microelectrodes and extracellular electrograms were record ed using a high-gain, signal averaging method DADs were induced by dig oxin (1.25 mu M, n = 9 fibers). After exposure to the drug for 20.8 +/ - 2.0 min at the pacing cycle lengths of 990, 690, and 490 msec, the D AD amplitudes were 3.7 +/- 0.3, 5.7 +/- 0.6, 6.4 +/- 0.8 mV respective ly The coupling intervals of DADs to the previous action potential at the same cycle lengths were 845.8 +/- 37.6, 581.3 +/- 23.1, 434.6 +/- 7.0 msec, respectively. Thus digoxin-induced DADs show typical frequen cy dependence. Digoxin-induced DADs also occasionally caused triggered action potentials. DADs also were recorded simultaneously using an ex tracellular signal averaging technique. DADs were easily detected an m ost of the DAD characteristics measured intracellular could be confirm ed in the extracellular electrograms. Digoxin induced a biphasic effec t on the action potential duration (measured at 50% of repolarization (APD(50)) and on the Q-T interval measured from the extracellular elec trograms, and in an additional group of fibers (n = 5) this was studie d in detail. Digoxin initially lengthened the APD(50) and the Q-T inte rval within the first 10 min of drug exposure, at a rime when DADs had nor yet developed. After this initial 10 min period of drug exposure, both APD(50) and Q-T interval were shortened significantly al the pac ing cycle lengths studied.