Abstract 5339: Structural Heterogeneity of the Ventricular Wall Modulates the Globally Applied Stretch to Impose Different Strain Condition to Local Myocardium and Evoke Focal Excitation
Arrhythmias are often observed when the ventricular wall is stretched under abnormal loading conditions. We assessed the hypothesis that, in dilated hearts, the structural heterogeneity of the ventricular wall imposes heterogeneous strain condition to local cardiomyocytes to provoke focal excitation and trigger arrhythmias. For this purpose, we examined the electrical responses of myocardium (membrane potential by voltage sensitive dye) to mechanical stresses at tissue (perfused right ventricular wall preparation, n=7) and cellular levels (isolated single myocytes, n=14). The membrane potential of cardiomyocytes obtained from the entire depth of the wall uniformly responded to the uniaxial stretch in an amplitude dependent manner. However, at the tissue level, although the uniform stretch was applied, the membrane potential was depolarized heterogeneously and action potential was evoked in the focal spot (Fig.1⇓). Morphometry revealed that these focal spots were concentrated in the thin region. Such spatial heterogeneity in electrical response became prominent when the global stretch of intermediate amplitude was applied because whole tissue responded to a large stretch. We could induce the spiral wave formation by stretch of intermediate amplitude in the simulation model of the tissue with structural heterogeneity (Fig.2⇓). In conclusion, the structural heterogeneity of the ventricular wall converts the globally applied stretch to apply different strain condition to each myocyte, especially under stretch of intermediate magnitude. The resultant electrical heterogeneity of the tissue could be the substrate and/or trigger for arrhythmias in diseased heart.