Membrane Time Constant During Internal Defibrillation Strength Shocks in Intact Heart: Effects of Na+ and Ca2+ Channel Blockers
This study was supported by American Heart Association grants 9960384 V and 0235172 N to Dr. Cheng, and NIH R01-HL67322 and R01-HL074283 to Dr. Efimov.
Manuscript received 25 April 2004; De novo manuscript received 8 June 2008; Accepted for publication 30 June 2008.
Abstract
Introduction: We assessed defibrillation strength shock-induced changes of the membrane time constant (τ) and membrane potential (ΔVm) in intact rabbit hearts after administration of lidocaine, a sodium (Na+) channel blocker, or nifedipine, a L-type calcium (Ca2+) channel blocker.
Methods and Results: We optically mapped anterior, epicardial, electrical activity during monophasic shocks (±100, ±130, ±160, ±190, and ±220 V; 150 μF; 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 μM, n = 6) or nifedipine (2μM, n = 6) addition. τ 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 ΔVm. We found (1) Under all conditions, there is inverse relationship between τ and ΔVm with respect to changes of shock strength, regardless of shock polarity and phase of application: a stronger shock resulted in a larger ΔVm, which corresponded to a smaller τ (faster cellular response); (2) Lidocaine did not cause appreciable changes in either τ or ΔVm versus control, and (3) Nifedipine significantly increased both τ and ΔVm in the virtual cathode area; in contrast, in the virtual anode area, this effect depended on the phase of shock application.
Conclusion: τ and ΔVm are inversely related. Na+ channel blocker has minimal impact on either τ or ΔVm. Ca2+ blocker caused polarity and phase-dependent significant changes in τ and ΔVm.
