Response of the Heart
to Strong Electric Fields

Although cardiac disease is the leading cause
of death in the Western world, key aspects of the electrical behavior of the heart are not yet well understood. For example, electrical defibrillation is an invaluable medical procedure, but the details of the mechanism by which strong electric fields interact with cardiac tissue and halt tachycardia and fibrillation are the subject of debate. While it is obvious that the defibrillation shock activates or inactivates regions of the heart that are distant from the site of stimulation, standard cable models of cardiac tissue would predict that such far-field stimulation would be ineffective more than a few millimeters from the stimulating electrode. The current view is that fiber curvature and intrinsic anatomical heterogeneities in the myocardium play crucial roles in the far-field stimulation observed in experiments. Heterogeneities in myocyte shape or connectivity, fiber bundle size and shape, extracellular fraction, and intra- or extracellular electrical conductivities would all affect the bidomain properties of cardiac tissue. Therefore they all could lead to a distribution of virtual cathodes and anodes throughout the tissue that would activate or inactivate tissue far from the stimulating electrodes. Despite numerous predictions, there are not yet any experimental results that provide a clear demonstration of the role of fiber curvature or heterogeneities in the defibrillation process. This ongoing research project is directed towards obtaining a clear and quantitative description of the role of fiber curvature and bidomain heterogeneities in cardiac defibrillation.

To image the effects of bidomain heterogeneities on far-field stimulation of the myocardium, we utilize optical imaging of the transmembrane potential (Vm) during field stimulation to examine the temporal and spatial responses. Two preparations have been used: the isolated whole rabbit heart and the isolated rabbit right ventricle. The preparation is Langendorff-perfused, stained with di-4-ANEPPS, and immersed in a bath of Tyrode's solution maintained at 37°C. The isolated whole heart preparation is perfused through the aorta, while the isolated right ventricle preparation is stretched across a plexiglass frame and perfused through the right coronary artery. The isolated right ventricle preparation is advantageous in that it eliminates the effects of the curved bath-bidomain boundary and allows direct visualization of both the epicardial and endocardial surfaces. Additionally there is no other chamber or septum to complicate activation pattern. Following 20 S1 pacing pulses from a point stimulus at a constant cycle length of 500 ms, a custom Ventritex computer-controlled stimulator delivers a 2-3 ms S2 to plate electrodes at the ends of the bath to produce horizontal shock fields of varying strengths. A high-speed 12-bit Dalsa CCD camera is used for optical imaging of Vm changes following S1 and during and after S2. A diode-pumped solid-state laser is used to illuminate the heart by means of multiple plastic optical fibers. In the whole heart preparation, endocardial illumination is achieved by fiber optics placed inside the left ventricle.

In our studies we have seen behavior in the isolated right ventricle that is consistent with our whole heart experiments. For the isolated whole heart under field stimulation, the externally applied electric field produces rapid depolarization of the half of the epicardium that faces the cathodal electrode, consistent with bidomain boundary effects. As shown in Figure 1, we have also seen these anodal and cathodal differences in the isolated right ventricle, although the endocardial activation patterns are more complex and heterogeneous than those observed on the epicardium.

Figure 1: Epicardial and Endocardial Images from Isolated Right Ventricle Preparation
View Larger Image (40K)

The right ventricle preparation allows direct comparison of endocardial and epicardial activation times. Analysis has shown that the activation times for the endocardium are shorter than the activation times for the epicardium for equal field strengths. This trend is depicted in Figure 3. The higher density of anatomical hetero-geneities on the endocardial surface may explain the more complex activation patterns and the shorter activation times observed for the endocardium

Figure 3: Plot of Activation Time vs Field Strength for the Right Ventricle Preparation (n=8)

View Larger Image (40K)

In conclusion, we have found that the activation from strong field shocks is rapid and non-propagative. Also, the initial distributed activation is not due to surface curvature effects because we are using the flat right ventricle preparation. We have observed that for a given field shock, activation time is shorter for the endocardium than for the epicardium. We have also determined that activation time decreases with increasing field shock strength for both endocardium and epicardium. These results have been observed in both the isolated whole heart and isolated right ventricle preparations.

Marcella Woods
marcella.c.woods@vanderbilt.edu