Membrane time constant during internal defibrillation strength shocks in intact heart: effects of Na+ and Ca2+ channel blockers.
BACKGROUND
We assessed defibrillation strength shock-induced changes of the membrane time constant (tau) and membrane potential (DeltaVm) in intact rabbit hearts after administration of lidocaine, a sodium (Na(+)) channel blocker, or nifedipine, a L-type calcium (Ca(2+)) channel blocker.


RESULTS
We optically mapped anterior, epicardial, electrical activity during monophasic shocks (+/-100, +/-130, +/-160, +/-190, and +/-220 V; 150 microF; 8 ms) applied at 25%, 50%, and 75% of the action potential duration via a shock lead system in Langendorff-perfused hearts. The protocol was run twice for each heart under control and after lidocaine (15 microM, n = 6) or nifedipine (2 microM, n = 6) addition. tau in the virtual electrode area away from the shock lead was approximated with single-exponential fits from a total of 121,125 recordings. The same data set was used to calculate DeltaVm. We found (1) Under all conditions, there is inverse relationship between tau and DeltaVm with respect to changes of shock strength, regardless of shock polarity and phase of application: a stronger shock resulted in a larger DeltaVm, which corresponded to a smaller tau (faster cellular response); (2) Lidocaine did not cause appreciable changes in either tau or DeltaVm versus control, and (3) Nifedipine significantly increased both tau and DeltaVm in the virtual cathode area; in contrast, in the virtual anode area, this effect depended on the phase of shock application.


CONCLUSIONS
tau and DeltaVm are inversely related. Na(+) channel blocker has minimal impact on either tau or DeltaVm. Ca(2+) blocker caused polarity and phase-dependent significant changes in tau and DeltaVm.
Mowrey
Kent A
KA
Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio 44195, USA.
Efimov
Igor R
IR
Cheng
Yuanna
Y
D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology*; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D004554:Electric Countershock / Q000379:methods*; D066298:In Vitro Techniques; D007700:Kinetics; D008012:Lidocaine / Q000008:administration & dosage; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D008955:Models, Cardiovascular; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology*; D009543:Nifedipine / Q000008:administration & dosage; D011817:Rabbits; D026941:Sodium Channel Blockers / Q000008:administration & dosage*
D002121:Calcium Channel Blockers; D026941:Sodium Channel Blockers; D008012:Lidocaine; D009543:Nifedipine
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