Despite recent advances in the understanding of the mechanisms of interaction between electric fields and cardiac cells, and in the development of implantable cardiac defibrillators (ICDs), the fundamental principles of defibrillation have yet to be formulated. Despite the existence of several competing theories of defibrillation, the search for new strategies and techniques to lower defibrillation threshold (DFT) continues to be purely empirical. Previous work by the applicant's laboratory has shown that defibrillatory shocks delivered to the heart through a transvenous catheter electrode produce spatially heterogeneous transmembrane potential responses on the ventricular epicardium so as to create """"""""virtual cathodes"""""""", which may lead to heterogeneous action potential prolongation. Thus it is hypothesized that success or failure of defibrillation depends on the ability of the shock to (1) extinguish preshock-fibrillatory activity; (2) prevent remaining wavelets from sustaining ventricular fibrillation; and (3) avoid creating phase singularities (critical points). The investigator propose to systematically map patterns of shock-induced polarization and post-shock action potential prolongation from the entire epicardium of the Langendorff-perfused rabbit heart, using a state-of-the-art imaging system in combination with a voltage sensitive dye. The system has high spatial resolution and signal-to-noise ratio and is immune to shock- induced recording artefacts, The modulation of spatio-temporal characteristics of the polarization will be studied, as well as the resulting action potential prolongation or shortening by (1) the shock waveform, (2) the phase of pre-shock electrical activity; (3) the geometry of the heart and defibrillation electrodes. Whole heart patterns of polarization and action potential prolongation will be correlated with success or failure to defibrillate and with the defibrillation threshold (DFT).
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