Cardiac conduction block and arrythmia termination by high frequency electric fields

Electrical signal conduction in cardiac and nervous tissue is fundamental to their physiological function. Irregular and disorganized patterns of electrical propagation in the brain and heart can lead to life-threatening conditions, including epileptic seizures and ventricular fibrillation (VF). Stimulation by high frequency alternating current (HFAC) electrical fields has previously been applied to nervous tissue to cause reversible conduction block, but has not be sufficiently explored in cardiac tissue. In this thesis, multiple species, models, and spatial scales, including cell monolayers, isolated hearts, and simulations of isolated myocytes and cardiac tissue, are used to assess the response in cardiac tissue to HFAC fields. It is shown that HFAC fields reversibly block electrical propagation by holding myocytes in a refractory state in which the cell transmembrane potential (Vm) is maintained at an elevated level for the field duration. HFAC fields that block electrical conduction also terminated reentrant arrhythmias, including VF. Vm-metrics, measured during the HFAC field, are dependent on field strength and frequency and significantly correlated with vulnerability to VF, predicting defibrillation success. Additionally, long-duration HFAC fields are shown to only transiently and to a small extent alter normal electrophysiological and mechanical function of the heart. Simulations demonstrate that HFAC fields maintain myocyte refractoriness by persistent activation of ionic currents, and conduction block is dependent on cell coupling and non-uniformities in the applied field.