title: Digoxin-induced delayed afterdepolarizations: biphasic effects of digoxin on action potential duration and the Q-T interval in cardiac Purkinje fibers.
abstract: Few reports exist of digoxin-induced delayed afterdepolarizations (DADs) and triggered activity recorded in cardiac fibers, and the electrophysiological characteristics of digoxin-induced DADs and triggered activity have not been reported in detail. We studied the electrophysiological properties of digoxin-induced DADs and triggered activity is sheep cardiac Purkinje fibers. Transmembrane voltage was recorded using conventional microelectrodes and extracellular electrograms were recorded using a high-gain, signal averaging method. DADs were induced by digoxin (1.25 microM, 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 DAD amplitudes were 3.7 +/- 0.3, 5.7 +/- 0.6, 6.4 +/- 0.8 mV, respectively. 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 frequency dependence. Digoxin-induced DADs also occasionally caused triggered action potentials. DADs also were recorded simultaneously using an extracellular signal averaging technique. DADs were easily detected an most of the DAD characteristics measured intracellular could be confirmed in the extracellular electrograms. Digoxin induced a biphasic effect on the action potential duration (measured at 50% of repolarization (APD50) and on the Q-T interval measured from the extracellular electrograms, and in an additional group of fibers (n = 5) this was studied in detail. Digoxin initially lengthened the APD50 and the Q-T interval within the first 10 min of drug exposure, at a time when DADs had not yet developed.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, University of Chicago, IL, USA.
authors.forename: J T
authors.initials: JT
authors.lastname: Xie
authors.forename: P M
authors.initials: PM
authors.lastname: Cunningham
authors.forename: C T
authors.initials: CT
authors.lastname: January
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004077:Digoxin / Q000494:pharmacology*; D004558:Electric Stimulation; D004562:Electrocardiography / Q000187:drug effects*; D004594:Electrophysiology; D006321:Heart / Q000294:innervation; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008839:Microelectrodes; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology*; D011690:Purkinje Fibers / Q000187:drug effects*; D012756:Sheep; D013997:Time Factors
chemical_list: D009467:Neuromuscular Depolarizing Agents; D004077:Digoxin