title: Refractory period prolongation by biphasic defibrillator waveforms is associated with enhanced sodium current in a computer model of the ventricular action potential.
abstract: Mechanisms through which biphasic waveforms lower defibrillation threshold are unknown. Previous work showed that low-intensity biphasic shocks (BS2), delivered during the refractory period of a control action potential (S1), produced significantly longer responses than monophasic shocks (MS2). To test the hypothesis that longer responses are due to hyperpolarization-induced excitation channel recovery during the first portion of the biphasic waveform, we used the Beeler-Reuter ventricular action potential computer model with the Drouhard-Roberge (BRDR) modification to study refractory period stimulation with MS2 (10 msec) and symmetrical BS2 (10 msec each pulse). At 1.5 times diastolic threshold, BS2 prolonged action potential duration when delivered 50 msec into the S1 refractory period, and produced a maximum BS2 versus MS2 response duration difference of 62 msec. Longer BS2 responses corresponded to enhanced BS2-induced sodium current compared to MS2. Maximum BS2 vs MS2 sodium current difference was 400 uA/cm2. These results show that, in a computer model of the ventricular action potential, hyperpolarization by the first phase of a biphasic waveform enhances S2 sodium current and prolongs duration of refractory-period responses. This effectively shortens the cellular refractory period. Prolonged refractory period responses, produced by biphasic defibrillator waveforms, may underlie enhanced defibrillating efficacy at low shock intensities.
authors.affiliation: Department of Physiology and Biophysics, Georgetown University, Washington, D.C.
authors.forename: J L
authors.initials: JL
authors.lastname: Jones
authors.forename: R E
authors.initials: RE
authors.lastname: Jones
authors.forename: K B
authors.initials: KB
authors.lastname: Milne
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D003198:Computer Simulation; D004554:Electric Countershock; D006801:Humans; D012032:Refractory Period, Electrophysiological / Q000502:physiology*; D012964:Sodium / Q000502:physiology*; D016276:Ventricular Function
chemical_list: D012964:Sodium