Hierarchical modeling of length-dependent force generation in cardiac muscles and associated thermodynamically-consistent numerical schemes

In the context of cardiac muscle modeling, the availability of the myosin heads in the sarcomeres varies over the heart cycle contributing to the Frank–Starling mechanism at the organ level. In this paper, we propose a new approach that allows to extend the Huxley’57 muscle contraction model equations to incorporate this variation. This extension is built in a thermodynamically consistent manner, and we also propose adapted numerical methods that satisfy thermodynamical balances at the discrete level. Moreover, this whole approach—both for the model and the numerics—is devised within a hierarchical strategy enabling the coupling of the microscopic sarcomere-level equations with the macroscopic tissue-level description. As an important illustration, coupling our model with a previously proposed simplified heart model, we demonstrate the ability of the modeling and numerical framework to capture the essential features of the Frank–Starling mechanism.

[1]  Michael W Gee,et al.  A monolithic 3D‐0D coupled closed‐loop model of the heart and the vascular system: Experiment‐based parameter estimation for patient‐specific cardiac mechanics , 2017, International journal for numerical methods in biomedical engineering.

[2]  Gernot Plank,et al.  Assessment of wall stresses and mechanical heart power in the left ventricle: Finite element modeling versus Laplace analysis , 2018, International journal for numerical methods in biomedical engineering.

[3]  P. D. de Tombe,et al.  The Frank-Starling mechanism is not mediated by changes in rate of cross-bridge detachment. , 1997, The American journal of physiology.

[4]  G. Piazzesi,et al.  Myosin filament activation in the heart is tuned to the mechanical task , 2017, Proceedings of the National Academy of Sciences.

[5]  John Jeremy Rice,et al.  A spatially detailed myofilament model as a basis for large-scale biological simulations , 2006, IBM J. Res. Dev..

[6]  P. D. de Tombe,et al.  An internal viscous element limits unloaded velocity of sarcomere shortening in rat myocardium. , 1992 .

[7]  Gustavo Stolovitzky,et al.  Ising model of cardiac thin filament activation with nearest-neighbor cooperative interactions. , 2003, Biophysical journal.

[8]  Takumi Washio,et al.  Approximation for Cooperative Interactions of a Spatially-Detailed Cardiac Sarcomere Model , 2012, Cellular and molecular bioengineering.

[9]  P. Burton,et al.  Effect of protein kinase A on calcium sensitivity of force and its sarcomere length dependence in human cardiomyocytes. , 2000, Cardiovascular research.

[10]  A. Quarteroni,et al.  Active contraction of cardiac cells: a reduced model for sarcomere dynamics with cooperative interactions , 2018, Biomechanics and modeling in mechanobiology.

[11]  A. Landesberg,et al.  The cross-bridge dynamics is determined by two length-independent kinetics: Implications on muscle economy and Frank-Starling Law. , 2016, Journal of molecular and cellular cardiology.

[12]  J. Rice,et al.  Approximate model of cooperative activation and crossbridge cycling in cardiac muscle using ordinary differential equations. , 2008, Biophysical journal.

[13]  A. Huxley,et al.  Proposed Mechanism of Force Generation in Striated Muscle , 1971, Nature.

[14]  Charles S. Peskin,et al.  Mathematical aspects of heart physiology , 1975 .

[15]  L Truskinovsky,et al.  Muscle as a metamaterial operating near a critical point. , 2013, Physical review letters.

[16]  P. D. de Tombe,et al.  Impact of temperature on cross‐bridge cycling kinetics in rat myocardium , 2007, The Journal of physiology.

[17]  D. Chapelle,et al.  Monitoring of cardiovascular physiology augmented by a patient-specific biomechanical model during general anesthesia. A proof of concept study , 2020, PloS one.

[18]  E. Starling,et al.  On the mechanical factors which determine the output of the ventricles , 1914, The Journal of physiology.

[19]  G. Piazzesi,et al.  The force and stiffness of myosin motors in the isometric twitch of a cardiac trabecula and the effect of the extracellular calcium concentration , 2018, The Journal of physiology.

[20]  T. L. Hill,et al.  A cross-bridge model of muscle contraction. , 1978, Progress in biophysics and molecular biology.

[21]  T. L. Hill,et al.  Cross-bridge model of muscle contraction. Quantitative analysis. , 1980, Biophysical journal.

[22]  V. Lombardi,et al.  Force and number of myosin motors during muscle shortening and the coupling with the release of the ATP hydrolysis products , 2015, The Journal of physiology.

[23]  H. T. ter Keurs,et al.  Cardiac muscle mechanics: Sarcomere length matters. , 2016, Journal of molecular and cellular cardiology.

[24]  A. Quarteroni,et al.  Thermodynamically consistent orthotropic activation model capturing ventricular systolic wall thickening in cardiac electromechanics , 2014 .

[25]  Takumi Washio,et al.  Multi-scale simulations of cardiac electrophysiology and mechanics using the University of Tokyo heart simulator. , 2012, Progress in biophysics and molecular biology.

[26]  G I Zahalak,et al.  A re-examination of calcium activation in the Huxley cross-bridge model. , 1997, Journal of biomechanical engineering.

[27]  Takumi Washio,et al.  Including Thermal Fluctuations in Actomyosin Stable States Increases the Predicted Force per Motor and Macroscopic Efficiency in Muscle Modelling , 2016, PLoS Comput. Biol..

[28]  P. D. de Tombe,et al.  Myofilament length-dependent activation develops within 5 ms in guinea-pig myocardium. , 2012, Biophysical journal.

[29]  Yutaka Kagaya,et al.  Sarcomere mechanics in uniform and non-uniform cardiac muscle: a link between pump function and arrhythmias. , 2008, Progress in biophysics and molecular biology.

[30]  A. Quarteroni,et al.  Biophysically detailed mathematical models of multiscale cardiac active mechanics , 2020, PLoS Comput. Biol..

[31]  T. Yanagida,et al.  Titin-mediated thick filament activation, through a mechanosensing mechanism, introduces sarcomere-length dependencies in mathematical models of rat trabecula and whole ventricle , 2017, Scientific Reports.

[32]  Silverthorn Dee Unglaub Human Physiology: An Integrated Approach , 1998 .

[33]  Alfio Quarteroni,et al.  Integrated Heart—Coupling multiscale and multiphysics models for the simulation of the cardiac function , 2017 .

[34]  P Moireau,et al.  Estimation of tissue contractility from cardiac cine-MRI using a biomechanical heart model , 2012, Biomechanics and modeling in mechanobiology.

[35]  Marco Linari,et al.  Size and speed of the working stroke of cardiac myosin in situ , 2016, Proceedings of the National Academy of Sciences.

[36]  Toshio Yanagida,et al.  From Single Molecule Fluctuations to Muscle Contraction: A Brownian Model of A.F. Huxley's Hypotheses , 2012, PloS one.

[37]  Claude Le Bris,et al.  Multiscale Modelling of Complex Fluids: A Mathematical Initiation , 2009 .

[38]  Christoph M. Augustin,et al.  Computational modeling of cardiac growth and remodeling in pressure overloaded hearts—Linking microstructure to organ phenotype , 2020, Acta biomaterialia.

[39]  L Truskinovsky,et al.  Mechanics of the power stroke in myosin II. , 2010, Physical review. E, Statistical, nonlinear, and soft matter physics.

[40]  John Jeremy Rice,et al.  Approaches to modeling crossbridges and calcium-dependent activation in cardiac muscle. , 2004, Progress in biophysics and molecular biology.

[41]  P. Tallec,et al.  An energy-preserving muscle tissue model: formulation and compatible discretizations , 2012 .

[42]  P. D. de Tombe,et al.  Cooperative activation in cardiac muscle: impact of sarcomere length. , 2002, American journal of physiology. Heart and circulatory physiology.

[43]  G. Zahalak The two-state cross-bridge model of muscle is an asymptotic limit of multi-state models. , 2000, Journal of theoretical biology.

[44]  M Caruel,et al.  Dimensional reductions of a cardiac model for effective validation and calibration , 2014, Biomechanics and modeling in mechanobiology.

[45]  Dan Cojoc,et al.  A myosin II nanomachine mimicking the striated muscle , 2018, Nature Communications.

[46]  A. Huxley Muscle structure and theories of contraction. , 1957, Progress in biophysics and biophysical chemistry.

[47]  Vasco Sequeira,et al.  The Frank–Starling Law: a jigsaw of titin proportions , 2017, Biophysical Reviews.

[48]  Kittipong Tachampa,et al.  Myofilament length dependent activation. , 2010, Journal of molecular and cellular cardiology.

[49]  Dominique Chapelle,et al.  Thermodynamic properties of muscle contraction models and associated discrete-time principles , 2019, Adv. Model. Simul. Eng. Sci..

[50]  Ellen Kuhl,et al.  The Living Heart Project: A robust and integrative simulator for human heart function. , 2014, European journal of mechanics. A, Solids.

[51]  Dominique Chapelle,et al.  Stochastic modeling of chemical–mechanical coupling in striated muscles , 2019, Biomechanics and Modeling in Mechanobiology.

[52]  G. Piazzesi,et al.  A cross-bridge model that is able to explain mechanical and energetic properties of shortening muscle. , 1995, Biophysical journal.

[53]  Jack Lee,et al.  Multiphysics and multiscale modelling, data–model fusion and integration of organ physiology in the clinic: ventricular cardiac mechanics , 2016, Interface Focus.

[54]  H. T. ter Keurs,et al.  Comparison between the Sarcomere Length‐Force Relations of Intact and Skinned Trabeculae from Rat Right Ventricle: Influence of Calcium Concentrations on These Relations , 1986, Circulation research.

[55]  H. E. Keurs,et al.  Cardiac muscle mechanics: Sarcomere length matters , 2016 .

[56]  Alf Månsson,et al.  Actomyosin-ADP states, interhead cooperativity, and the force-velocity relation of skeletal muscle. , 2010, Biophysical journal.