A Discrete Electromechanical Model for Human Cardiac Tissue: Effects of Stretch-Activated Currents and Stretch Conditions on Restitution Properties and Spiral Wave Dynamics

Abstract

We introduce an electromechanical model for human cardiac tissue which couples a biophysical model of cardiac excitation (Tusscher, Noble, Noble, Panfilov, 2006) and tension development (adjusted Niederer, Hunter, Smith, 2006 model) with a discrete elastic mass-lattice model. The equations for the excitation processes are solved with a finite difference approach, and the equations of the mass-lattice model are solved using Verlet integration. This allows the coupled problem to be solved with high numerical resolution. Passive mechanical properties of the mass-lattice model are described by a generalized Hooke's law for finite deformations (Seth material). Active mechanical contraction is initiated by changes of the intracellular calcium concentration, which is a variable of the electrical model. Mechanical deformation feeds back on the electrophysiology via stretch-activated ion channels whose conductivity is controlled by the local stretch of the medium. We apply the model to study how stretch-activated currents affect the action potential shape, restitution properties, and dynamics of spiral waves, under constant stretch, and dynamic stretch caused by active mechanical contraction. We find that stretch conditions substantially affect these properties via stretch-activated currents. In constantly stretched medium, we observe a substantial decrease in conduction velocity, and an increase of action potential duration; whereas, with dynamic stretch, action potential duration is increased only slightly, and the conduction velocity restitution curve becomes biphasic. Moreover, in constantly stretched medium, we find an increase of the core size and period of a spiral wave, but no change in rotation dynamics; in contrast, in the dynamically stretching medium, we observe spiral drift. Our results may be important to understand how altered stretch conditions affect the heart's functioning.

Cardiac contraction induces discordant alternans and localized block

“…The model shows that a small contraction effect suffices to induce the transition from concordant to dicordant alternans via its influence on the conduction velocity properties. In our model, stretch increases the conduction velocity, in accordance to what has been observed in other numerical studies under similar conditions [25]. The reason is that stretch opens the stretch activated channels, elevating the resting potential, thus making it easier to depolarize.…”

“…(1)- (4) we observe that the coupling with contraction changes the slope of the CV restitution curve, but not that of the APD restitution [Figs. 3(c) and 3(d)], consistent with results obtained in more realistic electromechanical models [25]. Thus, the onset of alternans (in cell) does not change, but the nature of alternans in tissue (either concordant or discordant) may change due to this coupling.…”

Biomechanics of Cardiac Electromechanical Coupling and Mechanoelectric Feedback

“…Computational simulations have suggested a role for nsMSCs in heart rate acceleration and deceleration due to stretch described above, and experimental evidence in SAN tissue using GsMTx-4 is in agreement [2,72]. Computational models and experiments studies suggest a role for nsMSCs in stretch-induced ectopic ventricular contractions, repolarization shortening, and rate-dependent restitution of action potential duration [44,[73][74][75].…”

The Rotor Revolution

“…Stretch-activated channels, demonstrated to be of importance in acute rhythm disturbances, such as commotio cordis, 55 will also have constitutive activity in chronic stretch. The intriguing finding that a tarantula venom peptide possesses antifibrillatory effects in rabbit hearts when mechanically loaded, mediated by its inhibition of stretchactivated channels, 56 shows how these can be specifically targeted.…”