MECHANOELECTRICAL FEEDBACK IN HEART: ARRHYTHMIAS

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An electrical network model of ventricular heart tissue was constructed from > 10,000 model cardiac myocytes. Each modeled myocyte is assembled from > 100 patches of membrane elements, consisting of membrane capacitance, represented by equivalent capacitor, membrane resistance, represented by equivalent resistor, voltage-gate sodium, potassium, calcium channels, and stretch-activated channels. Nonlinear electrical components modeling the dynamic behavior of ion channels in each membrane element were designed based on nonlinear differential equations and the experiment data of patch clamp on single cardiac myocyte. Membrane elements was connected longitudinally by passive resistive elements, and each modeled cell was connected laterally to adjacent modeled cell through a gap junction, represent by a resistor, forming a two dimensional modeled ventricular tissue. This approach shows that SPICE, a circuit simulator, on a supercomputer could provide the speed and accuracy necessary to accomplish the goal of this study. Our previous lab work on modeling single myocyte simulated on SPICE (PC version) demonstrated that the triggering of action current could be activated directly by current from stretch-activated channels, and blocking potassium channel both positively and negatively influences stretch-induced arrhythmias (SIAs). In this study, a bi-domain electrical network model of ventricular tissue, consisting of over hundred thousands of elements, combined with ion channels data can provide simulated view not only on cell level but also macrostructure level. A particular stimulus protocol was designed in this study to investigate the interaction between timing of ventricular stretch and other membrane currents, in determining conduction velocity, charge threshold, and action potential duration. The goal of the research is to find new strategies for treating arrhythmais.