Electromechanical wavebreak in a model of the human left ventricle.

In the present report, we introduce an integrative three-dimensional electromechanical model of the left ventricle of the human heart. Electrical activity is represented by the ionic TP06 model for human cardiac cells, and mechanical activity is represented by the Niederer-Hunter-Smith active contractile tension model and the exponential Guccione passive elasticity model. These models were embedded into an anatomic model of the left ventricle that contains a detailed description of cardiac geometry and the fiber orientation field. We demonstrated that fiber shortening and wall thickening during normal excitation were qualitatively similar to experimental recordings. We used this model to study the effect of mechanoelectrical feedback via stretch-activated channels on the stability of reentrant wave excitation. We found that mechanoelectrical feedback can induce the deterioration of an otherwise stable spiral wave into turbulent wave patterns similar to that of ventricular fibrillation. We identified the mechanisms of this transition and studied the three-dimensional organization of this mechanically induced ventricular fibrillation.

[1]  Andrew D McCulloch,et al.  Laminar fiber architecture and three-dimensional systolic mechanics in canine ventricular myocardium. , 1999, American journal of physiology. Heart and circulatory physiology.

[2]  A. Hodgkin,et al.  A quantitative description of membrane current and its application to conduction and excitation in nerve , 1990 .

[3]  R S Reneman,et al.  Dependence of local left ventricular wall mechanics on myocardial fiber orientation: a model study. , 1992, Journal of biomechanics.

[4]  P Kohl,et al.  Cellular mechanisms of cardiac mechano-electric feedback in a mathematical model. , 1998, The Canadian journal of cardiology.

[5]  A. J. Pullan,et al.  Geometric modeling of the human torso using cubic hermite elements , 2007, Annals of Biomedical Engineering.

[6]  P. Hunter,et al.  Computational mechanics of the heart : From tissue structure to ventricular function , 2000 .

[7]  R. Gray,et al.  Spatial and temporal organization during cardiac fibrillation , 1998, Nature.

[8]  黄亚明 MedScape , 2009 .

[9]  P. Hunter,et al.  Mathematical model of geometry and fibrous structure of the heart. , 1991, The American journal of physiology.

[10]  Martyn P. Nash,et al.  Modeling cardiac mechano-electrical feedback using reaction-diffusion-mechanics systems , 2009 .

[11]  P. Taggart,et al.  Inhomogeneous transmural conduction during early ischaemia in patients with coronary artery disease. , 2000, Journal of molecular and cellular cardiology.

[12]  Shien-Fong Lin,et al.  Spatial Distribution of Phase Singularities in Ventricular Fibrillation , 2003, Circulation.

[13]  Jian Huang,et al.  Evolution of activation patterns during long-duration ventricular fibrillation in pigs. , 2004, American journal of physiology. Heart and circulatory physiology.

[14]  S. Niederer,et al.  An improved numerical method for strong coupling of excitation and contraction models in the heart. , 2008, Progress in biophysics and molecular biology.

[15]  J. Nenonen,et al.  Simulated Epicardial Potential Maps During Paced Activation Reflect Myocardial Fibrous Structure , 1998, Annals of Biomedical Engineering.

[16]  E. Rowland,et al.  Dispersion of monophasic action potential duration: demonstrable in humans after premature ventricular extrastimulation but not in steady state. , 1992, Journal of the American College of Cardiology.

[17]  J. Hancox,et al.  Gadolinium inhibits Na+‐Ca2+ exchanger current in guinea‐pig isolated ventricular myocytes , 2000, British journal of pharmacology.

[18]  Viatcheslav Gurev,et al.  Mechanisms of Mechanically Induced Spontaneous Arrhythmias in Acute Regional Ischemia , 2010, Circulation research.

[19]  Arun V. Holden,et al.  Tension of organizing filaments of scroll waves , 1994, Philosophical Transactions of the Royal Society of London. Series A: Physical and Engineering Sciences.

[20]  P. Hunter,et al.  Stretch-induced changes in heart rate and rhythm: clinical observations, experiments and mathematical models. , 1999, Progress in biophysics and molecular biology.

[21]  O. Berenfeld,et al.  Effect of remodelling, stretch and ischaemia on ventricular fibrillation frequency and dynamics in a heart failure model. , 2005, Cardiovascular research.

[22]  A. McCulloch,et al.  Measurement of strain and analysis of stress in resting rat left ventricular myocardium. , 1993, Journal of biomechanics.

[23]  M P Nash,et al.  Self-organized pacemakers in a coupled reaction-diffusion-mechanics system. , 2005, Physical review letters.

[24]  A. Pertsov,et al.  Ventricular ¯brillation: Evolution of the Multiple-wavelet Hypothesis , 2001 .

[25]  R. Coronel,et al.  Mechanical effects on arrhythmogenesis: from pipette to patient. , 2003, Progress in biophysics and molecular biology.

[26]  Ursula Ravens,et al.  Mechano-electric feedback and arrhythmias. , 2003, Progress in biophysics and molecular biology.

[27]  M R Franz,et al.  Gadolinium decreases stretch-induced vulnerability to atrial fibrillation. , 2000, Circulation.

[28]  Martyn P. Nash,et al.  Evidence for Multiple Mechanisms in Human Ventricular Fibrillation , 2006, Circulation.

[29]  H Zhang,et al.  Mathematical models of action potentials in the periphery and center of the rabbit sinoatrial node. , 2000, American journal of physiology. Heart and circulatory physiology.

[30]  A. Guyton,et al.  Textbook of Medical Physiology , 1961 .

[31]  M. Nash,et al.  Electromechanical model of excitable tissue to study reentrant cardiac arrhythmias. , 2004, Progress in biophysics and molecular biology.

[32]  Kumaraswamy Nanthakumar,et al.  Epicardial organization of human ventricular fibrillation. , 2004, Heart rhythm.

[33]  M P Nash,et al.  Organization of ventricular fibrillation in the human heart: experiments and models , 2009, Experimental physiology.

[34]  James P. Keener,et al.  Mathematical physiology , 1998 .

[35]  R. Clayton,et al.  Whole heart action potential duration restitution properties in cardiac patients: a combined clinical and modelling study , 2006, Experimental physiology.

[36]  Hiroshi Ashikaga,et al.  Transmural mechanics at left ventricular epicardial pacing site. , 2004, American journal of physiology. Heart and circulatory physiology.

[37]  C. Herrmann,et al.  Early steps of the Mg(2+)-ATPase of relaxed myofibrils. A comparison with Ca(2+)-activated myofibrils and myosin subfragment 1. , 1992, Biochemistry.

[38]  Roy C. P. Kerckhoffs,et al.  Coupling of a 3D Finite Element Model of Cardiac Ventricular Mechanics to Lumped Systems Models of the Systemic and Pulmonic Circulation , 2006, Annals of Biomedical Engineering.

[39]  P. Hunter,et al.  Modelling the mechanical properties of cardiac muscle. , 1998, Progress in biophysics and molecular biology.

[40]  A Murray,et al.  Objective features of the surface electrocardiogram during ventricular tachyarrhythmias. , 1995, European heart journal.

[41]  A D McCulloch,et al.  Left ventricular epicardial deformation in isolated arrested dog heart. , 1987, The American journal of physiology.

[42]  Negative filament tension in the Luo-Rudy model of cardiac tissue. , 2007, Chaos.

[43]  G. Bett,et al.  Stretch-activated whole cell currents in adult rat cardiac myocytes. , 2000, American journal of physiology. Heart and circulatory physiology.

[44]  K. T. ten Tusscher,et al.  Alternans and spiral breakup in a human ventricular tissue model. , 2006, American journal of physiology. Heart and circulatory physiology.

[45]  F. Sachs,et al.  Calcium imaging of mechanically induced fluxes in tissue-cultured chick heart: role of stretch-activated ion channels. , 1992, The American journal of physiology.

[46]  P. Hunter,et al.  Computational Mechanics of the Heart , 2000 .

[47]  W C Hunter,et al.  A method to reconstruct myocardial sarcomere lengths and orientations at transmural sites in beating canine hearts. , 1992, The American journal of physiology.

[48]  Chiara Tesi,et al.  Tension generation and relaxation in single myofibrils from human atrial and ventricular myocardium , 2007, Pflügers Archiv - European Journal of Physiology.

[49]  W. Baxter,et al.  Stationary and drifting spiral waves of excitation in isolated cardiac muscle , 1992, Nature.

[50]  D. Rosenbaum,et al.  Optical mapping in a new guinea pig model of ventricular tachycardia reveals mechanisms for multiple wavelengths in a single reentrant circuit. , 1996, Circulation.

[51]  L. J. Leon,et al.  Spatiotemporal evolution of ventricular fibrillation , 1998, Nature.

[52]  黄亚明 eMedicine , 2009 .

[53]  M P Nash,et al.  Drift and breakup of spiral waves in reaction–diffusion–mechanics systems , 2007, Proceedings of the National Academy of Sciences.

[54]  N. Simionescu,et al.  The Cardiovascular System , 1983 .

[55]  H. T. ter Keurs,et al.  Tension Development and Sarcomere Length in Rat Cardiac Trabeculae: Evidence of Length‐Dependent Activation , 1980, Circulation research.

[56]  Peter Kohl,et al.  Effect of stretch-activated channels on defibrillation efficacy. , 2004, Heart rhythm.

[57]  F. Fenton,et al.  Vortex dynamics in three-dimensional continuous myocardium with fiber rotation: Filament instability and fibrillation. , 1998, Chaos.

[58]  G. Salama,et al.  Optical Imaging of the Heart , 2004, Circulation research.

[59]  D. Bers,et al.  Temperature dependence of myofilament Ca sensitivity of rat, guinea pig, and frog ventricular muscle. , 1990, The American journal of physiology.

[60]  W. Parmley,et al.  Relation between mechanics of contraction and relaxation in mammalian cardiac muscle. , 1969, The American journal of physiology.

[61]  T. Arts,et al.  Characterization of the normal cardiac myofiber field in goat measured with MR-diffusion tensor imaging. , 2002, American journal of physiology. Heart and circulatory physiology.

[62]  A. McCulloch,et al.  Passive material properties of intact ventricular myocardium determined from a cylindrical model. , 1991, Journal of biomechanical engineering.

[63]  S. Siegelbaum,et al.  Single sodium channels from canine ventricular myocytes: voltage dependence and relative rates of activation and inactivation. , 1989, The Journal of physiology.

[64]  P. Hunter,et al.  A quantitative analysis of cardiac myocyte relaxation: a simulation study. , 2006, Biophysical journal.

[65]  F Sachs,et al.  Stretch-activated ion channels in the heart. , 1997, Journal of molecular and cellular cardiology.

[66]  R Wilders,et al.  Gap junctions in cardiovascular disease. , 2000, Circulation research.

[67]  M. P. Nash,et al.  A computational study of mother rotor VF in the human ventricles , 2008, American journal of physiology. Heart and circulatory physiology.

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

[69]  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.

[70]  Jian Huang,et al.  Evolution of activation patterns during long-duration ventricular fibrillation in dogs. , 2004, American journal of physiology. Heart and circulatory physiology.

[71]  L. E. Malvern Introduction to the mechanics of a continuous medium , 1969 .

[72]  M. Fishbein,et al.  Characteristics of wave fronts during ventricular fibrillation in human hearts with dilated cardiomyopathy: role of increased fibrosis in the generation of reentry. , 1998, Journal of the American College of Cardiology.

[73]  Alexander V Panfilov,et al.  Organization of Ventricular Fibrillation in the Human Heart , 2007, Circulation research.

[74]  A. McCulloch,et al.  Mechanoelectric Feedback in a Model of the Passively Inflated Left Ventricle , 2001, Annals of Biomedical Engineering.