Basic mechanisms of heart defibrillation. An investigation by optical high-resolution potential mapping and methematicalmodelling

A successful defibrillation treatment implies the electrical interaction with even those cardiomyocytes, which are situated far from the electrodes. In homogeneous cables or syncytia, as predicted by theory, shock induced transmembrane potential changes with increasing distance from electrodes drop quickly to insufficiently small values. Our experiments gave clear evidence, that structural inhomogeneities, sized within about 0.1 to 1 mm, were able to cause strong membrane polarizations far from the electrodes, which are supposed to be sufficient to stop fibrillation. We have performed optical potential mapping with very high temporal (about 0.01 ms to 0.1 ms) and spatial (about 0.01 mm to 0.1 mm) resolution in guinea pig isolated ventricular cells and papillary muscles during the application of electrical pulses. In isolated cardiomyocytes, the results of field stimulation experiments were compared to corresponding simulation studies using a one-dimensional approximation of the cell. Augmenting the experimental results with those of simulation studies allowed us to study not directly observable quantities such as e.g. current densities. In addition, voltage-clamp experiments during optical monitoring of the membrane potential were performed. These experiments revealed membrane currents appearing at higher voltages, which are not included in standard membrane kinetic models (Luo-Rudy), but which are necessary to describe the electrical behavior during field stimulation. In papillary muscles, by changing the objectives of the optical setup, the monitored area, containing 64 measuring spots, varied from 0.1 x 0.1 mm to 1 x 1 mm. The field induced membrane potential changes were often caused to a high degree by small tissue inhomogeneities. The evaluation of several experiments allowed us to gain mean values and mean spatial distributions of these field induced membrane voltages: we found two maxima, one at a distance of about 0.6 mm, and one at about 0.1 mm. Whereas the latter distance fits close to a cell length, the distance of 0.6 mm is most likely related to non conducting sheets in the tissue. In two experiments, in a monitored area of 1 mm x 1 mm, and 0.16 mm x 0.16 mm respectively, exceeding a field strength of about 4 V/cm, the field induced membrane voltages were high enough to trigger local electrical activities (i.e. an action potential). These findings are a strong hint that even tiny inhomogeneities of the tissue structure may be sufficient to generate membrane polarizations far from electrodes, which are able to serve for a successful defibrillation treatment. In a series of experiments, the setup was adapted by introducing pinholes into the light paths for confocal measurements. This allowed us to perform optical potential measurements at up to 6 measuring spots simultaneously with a resolution depth of about 0.015 mm, which is about a cell layer. In such an experiment, within a depth of about 0.04 mm (which is 2 to 3 cell layers) a simultaneous occurring depolarization and hyperpolarization within the same measuring spot were found. It is supposed, that also these kinds of inhomogeneity may contribute to a successful defibrillation. In addition, the experiments have demonstrated the importance of optical membrane potential measurements, which allow us to gain results unattainable by other methods.