Direct measurements of membrane time constant during defibrillation strength shocks

Background: Defibrillation shocks impose significant energy demand on implantable cardioverter-defibrillators (ICDs). Several modeling studies have been devoted to optimizing shock parameters, and a large number of these studies treat the heart as a simplified lumped network. The time constant of membrane polarization (τ_m) is a key variable for such modeling efforts. Objective: The purpose of this study was to perform direct measurements of transmembrane potential (V_m) during defibrillation strength shocks and estimate τ_m of membrane polarization. Methods: A portion of the left ventricular epicardial surface of Langendorff-perfused rabbit hearts was stimulated using uniform electric fields produced by two parallel line electrodes. The V_ms were recorded from di-4-ANEPPS-stained hearts using a multisite optical mapping system. The hearts were paced with 20 S1 pulses from the apex, and shocks (S2: 5, 10, 20 V/cm) were applied via the line electrodes during the action potential of the 20th S1 at two different coupling intervals (S1S2: 120 and 180 ms). Residual responses were obtained by subtracting responses to the 19th S1 from the responses to the 20th S1S2 pair and used for time-constant analysis by fitting a monoexponential function. Results: τ_m exhibited a large variation and ranged from ∼1 to 30 ms. Furthermore, τ_m varied with electric field strength, S1S2 interval, position of the tissue from stimulating electrodes, and polarity of the response. To a large extent, the effects of all these factors were captured in a single parameter-the change in transmembrane voltage (ΔV_m) in response to the applied field (E). τ_m showed a monotonically decreasing trend with ΔV_m for all Es and S1S2s. Conclusion: Time constant of membrane polarization varies significantly during defibrillation strength shocks and shows a strong dependence on ΔV_m.