In this study, the cardiac electro-mechanical model in a deforming domain is taken with the addition of mechanical feedback and stretch-activated channel current coupled with the ten Tusscher human ventricular cell level model that results in a coupled PDE–ODE system. The existence and uniqueness of such a coupled system in a deforming domain is proved. At first, the existence of a solution is proved in the deformed domain. The local existence of the solution is proved using the regularization and the Faedo–Galerkin technique. Then, the global existence is proved using the energy estimates in appropriate Banach spaces, Gronwall lemma, and the compactness procedure. The existence of the solution in an undeformed domain is proved using the lower semi-continuity of the norms. Uniqueness is proved using Young’s inequality, Gronwall lemma, and the Cauchy–Schwartz inequality. For the application purpose, this model is applied to understand the electro-mechanical activity in ischemic cardiac tissue. It also takes care of the development of active tension, conductive, convective, and ionic feedback. The Second Piola–Kirchoff stress tensor arising in Lagrangian mapping between reference and moving frames is taken as a combination of active, passive, and volumetric components. We investigated the effect of varying strength of hyperkalemia and hypoxia, in the ischemic subregions of human cardiac tissue with local multiple ischemic subregions, on the electro-mechanical activity of healthy and ischemic zones. This system is solved numerically using the Q1 finite element method in space and the implicit–explicit Euler method in time. Discontinuities arising with the modeled multiple ischemic regions are treated to the desired order of accuracy by a simple regularization technique using the interpolating polynomials. We examined the cardiac electro-mechanical activity for several cases in multiple hyperkalemic and hypoxic human cardiac tissue. We concluded that local multiple ischemic subregions severely affect the cardiac electro-mechanical activity more, in terms of action potential (v) and mechanical parameters, intracellular calcium ion concentration [Ca2+]i, active tension (TA), stretch (λ) and stretch rate (dλdt), of a healthy cell in its vicinity, compared to a single Hyperkalemic or Hypoxic subregion. The four moderate hypoxically generated ischemic subregions affect the waveform of the stretch along the fiber and the stretch rate more than a single severe ischemic subregion.

Cardiac electro-mechanical activity in a deforming human cardiac tissue: modeling, existence–uniqueness, finite element computation and application to multiple ischemic disease / M. Pargaei, B.V.R. Kumar, L.F. Pavarino, S. Scacchi. - In: JOURNAL OF MATHEMATICAL BIOLOGY. - ISSN 0303-6812. - 84:3(2022), pp. 17.1-17.42. [10.1007/s00285-022-01717-3]

Cardiac electro-mechanical activity in a deforming human cardiac tissue: modeling, existence–uniqueness, finite element computation and application to multiple ischemic disease

L.F. Pavarino;S. Scacchi
2022

Abstract

In this study, the cardiac electro-mechanical model in a deforming domain is taken with the addition of mechanical feedback and stretch-activated channel current coupled with the ten Tusscher human ventricular cell level model that results in a coupled PDE–ODE system. The existence and uniqueness of such a coupled system in a deforming domain is proved. At first, the existence of a solution is proved in the deformed domain. The local existence of the solution is proved using the regularization and the Faedo–Galerkin technique. Then, the global existence is proved using the energy estimates in appropriate Banach spaces, Gronwall lemma, and the compactness procedure. The existence of the solution in an undeformed domain is proved using the lower semi-continuity of the norms. Uniqueness is proved using Young’s inequality, Gronwall lemma, and the Cauchy–Schwartz inequality. For the application purpose, this model is applied to understand the electro-mechanical activity in ischemic cardiac tissue. It also takes care of the development of active tension, conductive, convective, and ionic feedback. The Second Piola–Kirchoff stress tensor arising in Lagrangian mapping between reference and moving frames is taken as a combination of active, passive, and volumetric components. We investigated the effect of varying strength of hyperkalemia and hypoxia, in the ischemic subregions of human cardiac tissue with local multiple ischemic subregions, on the electro-mechanical activity of healthy and ischemic zones. This system is solved numerically using the Q1 finite element method in space and the implicit–explicit Euler method in time. Discontinuities arising with the modeled multiple ischemic regions are treated to the desired order of accuracy by a simple regularization technique using the interpolating polynomials. We examined the cardiac electro-mechanical activity for several cases in multiple hyperkalemic and hypoxic human cardiac tissue. We concluded that local multiple ischemic subregions severely affect the cardiac electro-mechanical activity more, in terms of action potential (v) and mechanical parameters, intracellular calcium ion concentration [Ca2+]i, active tension (TA), stretch (λ) and stretch rate (dλdt), of a healthy cell in its vicinity, compared to a single Hyperkalemic or Hypoxic subregion. The four moderate hypoxically generated ischemic subregions affect the waveform of the stretch along the fiber and the stretch rate more than a single severe ischemic subregion.
Coupled PDE–ODEs; Electro-mechanical coupling; Existence–uniqueness; Faedo Galerkin method; Finite element method; Multiple cardiac ischemia; Action Potentials; Electric Conductivity; Finite Element Analysis; Humans; Algorithms; Heart
Settore MAT/08 - Analisi Numerica
2022
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/925607
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