INTRODUCTION: Implantable cardioverter defibrillator (ICD) therapy is a well-established therapy for treating patients at high risk for sudden cardiac death. Recently formulated virtual electrode polarization theory is a promising foundation for the theory of defibrillation. Yet, continuing optimization of defibrillation therapy is limited to primarily empirical methods due to difficulties in assessing kinetics of cellular response in whole heart models of defibrillation. The aim of this study was to evaluate the response of the myocardium in the context of virtual electrode polarization. METHODS AND RESULTS: We used a Langendorff-perfused rabbit heart model of ICD therapy and voltage-sensitive fluorescent dye imaging in order to map kinetics of trans membrane potential during both mono- and biphasic shocks applied at various phases of the QT-interval. Cellular response was fitted to a single exponential function using the Levenberg-Marquardt method. Time constants (tau) were measured in 45 288 optical records from 17 hearts. We found that cellular response depends upon both QT-phase of application, intensity, polarity, and phase of the biphasic waveform. Shocks of larger strengths produce a faster response. The tau of the first-phase negatively polarizing response was significantly larger compared with the positively polarizing response at intensities below 200 V, but smaller at 200 V and above. The tau of the second phase negatively polarizing response was always slower than the positively polarizing response, regardless of amplitude, and timing. Overall, tau ranged from 1.6 ms to 14.2 ms. CONCLUSIONS: The time constant of the membrane depends on the field, action potential phase and the shock polarity, but exceeds 1 msec. Therefore, we suggest using a slower shock leading edge, since the membrane cannot follow potentially damaging faster waveforms.
INTRODUCTION: Implantable cardioverter defibrillator (ICD) therapy is a well-established therapy for treating patients at high risk for sudden cardiac death. Recently formulated virtual electrode polarization theory is a promising foundation for the theory of defibrillation. Yet, continuing optimization of defibrillation therapy is limited to primarily empirical methods due to difficulties in assessing kinetics of cellular response in whole heart models of defibrillation. The aim of this study was to evaluate the response of the myocardium in the context of virtual electrode polarization. METHODS AND RESULTS: We used a Langendorff-perfused rabbit heart model of ICD therapy and voltage-sensitive fluorescent dye imaging in order to map kinetics of trans membrane potential during both mono- and biphasic shocks applied at various phases of the QT-interval. Cellular response was fitted to a single exponential function using the Levenberg-Marquardt method. Time constants (tau) were measured in 45 288 optical records from 17 hearts. We found that cellular response depends upon both QT-phase of application, intensity, polarity, and phase of the biphasic waveform. Shocks of larger strengths produce a faster response. The tau of the first-phase negatively polarizing response was significantly larger compared with the positively polarizing response at intensities below 200 V, but smaller at 200 V and above. The tau of the second phase negatively polarizing response was always slower than the positively polarizing response, regardless of amplitude, and timing. Overall, tau ranged from 1.6 ms to 14.2 ms. CONCLUSIONS: The time constant of the membrane depends on the field, action potential phase and the shock polarity, but exceeds 1 msec. Therefore, we suggest using a slower shock leading edge, since the membrane cannot follow potentially damaging faster waveforms.
Authors: Frency Varghese; Johanna U Neuber; Fei Xie; Jonathan M Philpott; Andrei G Pakhomov; Christian W Zemlin Journal: Cardiovasc Res Date: 2017-12-01 Impact factor: 10.787