The role of infarct transmural extent in infarct extension: A computational study

Infarct extension, a process involving progressive extension of the infarct zone (IZ) into the normally perfused border zone (BZ), leads to continuous degradation of the myocardial function and adverse remodelling. Despite carrying a high risk of mortality, detailed understanding of the mechanisms leading to BZ hypoxia and infarct extension remains unexplored. In the present study, we developed a 3D truncated ellipsoidal left ventricular model incorporating realistic electromechanical properties and fibre orientation to examine the mechanical interaction among the remote, infarct and BZs in the presence of varying infarct transmural extent (TME). Localized highly abnormal systolic fibre stress was observed at the BZ, owing to the simultaneous presence of moderately increased stiffness and fibre strain at this region, caused by the mechanical tethering effect imposed by the overstretched IZ. Our simulations also demonstrated the greatest tethering effect and stress in BZ regions with fibre direction tangential to the BZ-remote zone boundary. This can be explained by the lower stiffness in the cross-fibre direction, which gave rise to a greater stretching of the IZ in this direction. The average fibre strain of the IZ, as well as the maximum stress in the sub-endocardial layer, increased steeply from 10% to 50% infarct TME, and slower thereafter. Based on our stress-strain loop analysis, we found impairment in the myocardial energy efficiency and elevated energy expenditure with increasing infarct TME, which we believe to place the BZ at further risk of hypoxia. Copyright © 2016 John Wiley & Sons, Ltd.

[1]  Jiun-Jr Wang,et al.  Expanding application of the Wiggers diagram to teach cardiovascular physiology. , 2014, Advances in physiology education.

[2]  Mark Potse,et al.  A Comparison of Monodomain and Bidomain Reaction-Diffusion Models for Action Potential Propagation in the Human Heart , 2006, IEEE Transactions on Biomedical Engineering.

[3]  Olaf Dössel,et al.  Modeling of cardiac ischemia in human myocytes and tissue including spatiotemporal electrophysiological variations / Modellierung kardialer Ischämie in menschlichen Myozyten und Gewebe , 2009, Biomedizinische Technik. Biomedical engineering.

[4]  Jianwen Wang,et al.  Preserved left ventricular twist and circumferential deformation, but depressed longitudinal and radial deformation in patients with diastolic heart failure. , 2007, European heart journal.

[5]  Jerry L Prince,et al.  Assessment of distribution and evolution of Mechanical dyssynchrony in a porcine model of myocardial infarction by cardiovascular magnetic resonance , 2012, Journal of Cardiovascular Magnetic Resonance.

[6]  S. Humphries,et al.  Left Ventricular Wall Thickness and the Presence of Asymmetric Hypertrophy in Healthy Young Army Recruits: Data From the LARGE Heart Study , 2013, Circulation. Cardiovascular imaging.

[7]  Impact of transmural necrosis on left ventricular remodeling and clinical outcomes in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction , 2013, The International Journal of Cardiovascular Imaging.

[8]  Roy C. P. Kerckhoffs,et al.  Effects of biventricular pacing and scar size in a computational model of the failing heart with left bundle branch block , 2009, Medical Image Anal..

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

[10]  Piet Claus,et al.  Left-ventricular shape determines intramyocardial mechanical heterogeneity. , 2011, American journal of physiology. Heart and circulatory physiology.

[11]  Mirza Faisal Beg,et al.  Measuring and Mapping Cardiac Fiber and Laminar Architecture Using Diffusion Tensor MR Imaging , 2005, Annals of the New York Academy of Sciences.

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

[13]  Lik Chuan Lee,et al.  First evidence of depressed contractility in the border zone of a human myocardial infarction. , 2012, The Annals of thoracic surgery.

[14]  Y. Pinto,et al.  Molecular mechanisms that control interstitial fibrosis in the pressure-overloaded heart. , 2011, Cardiovascular research.

[15]  H. White,et al.  Acute myocardial infarction , 2008, The Lancet.

[16]  J. Guccione,et al.  MRI-based finite-element analysis of left ventricular aneurysm. , 2005, American journal of physiology. Heart and circulatory physiology.

[17]  J. R. Fitzpatrick,et al.  Myocardial tissue elastic properties determined by atomic force microscopy after stromal cell-derived factor 1α angiogenic therapy for acute myocardial infarction in a murine model. , 2012, The Journal of thoracic and cardiovascular surgery.

[18]  Liang Ge,et al.  Comparison of the Young-Laplace law and finite element based calculation of ventricular wall stress: implications for postinfarct and surgical ventricular remodeling. , 2011, The Annals of thoracic surgery.

[19]  L. Ge,et al.  Left ventricular myocardial contractility is depressed in the borderzone after posterolateral myocardial infarction. , 2013, Annals of Thoracic Surgery.

[20]  D K Bogen,et al.  Changes in passive mechanical stiffness of myocardial tissue with aneurysm formation. , 1994, Circulation.

[21]  E. Leifer,et al.  Transmural dispersion of myofiber mechanics: implications for electrical heterogeneity in vivo. , 2006, Journal of the American College of Cardiology.

[22]  Gregory M. Fomovsky,et al.  Model-Based Design of Mechanical Therapies for Myocardial Infarction , 2011, Journal of cardiovascular translational research.

[23]  Stefan Neubauer,et al.  Dynamic Changes of Edema and Late Gadolinium Enhancement After Acute Myocardial Infarction and Their Relationship to Functional Recovery and Salvage Index , 2011, Circulation. Cardiovascular imaging.

[24]  Samuel T Wall,et al.  Electromechanical feedback with reduced cellular connectivity alters electrical activity in an infarct injured left ventricle: a finite element model study. , 2012, American journal of physiology. Heart and circulatory physiology.

[25]  Nigel H. Lovell,et al.  Electromechanics modeling of the effects of myocardial infarction on left ventricular function , 2015, 2015 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC).

[26]  Richard D. White,et al.  Assessment of Left Ventricular Torsional Deformation by Doppler Tissue Imaging: Validation Study With Tagged Magnetic Resonance Imaging , 2004, Circulation.

[27]  P. Anversa,et al.  Left ventricular failure induced by myocardial infarction. II. Tissue morphometry. , 1985, The American journal of physiology.

[28]  M. Ratcliffe Non-ischemic infarct extension: A new type of infarct enlargement and a potential therapeutic target*☆ , 2002 .

[29]  S. Kaul,et al.  There may be more to myocardial viability than meets the eye. , 1995, Circulation.

[30]  J. Pilla,et al.  Cardiac Support Device Modifies Left Ventricular Geometry and Myocardial Structure After Myocardial Infarction , 2005, Circulation.

[31]  P. Anversa,et al.  Left ventricular failure induced by myocardial infarction. I. Myocyte hypertrophy. , 1985, The American journal of physiology.

[32]  Y. Rudy,et al.  Activation and repolarization of the normal human heart under complete physiological conditions. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[33]  E. McVeigh,et al.  Electromechanical analysis of infarct border zone in chronic myocardial infarction. , 2005, American journal of physiology. Heart and circulatory physiology.

[34]  Toshiaki Hisada,et al.  Finite Element Analysis of Ventricular Wall Motion and Intra-Ventricular Blood Flow in Heart with Myocardial Infarction , 2004 .

[35]  William R Wagner,et al.  Intra-myocardial biomaterial injection therapy in the treatment of heart failure: Materials, outcomes and challenges. , 2011, Acta biomaterialia.

[36]  G. Dorn,et al.  Inhibition of ischemic cardiomyocyte apoptosis through targeted ablation of Bnip3 restrains postinfarction remodeling in mice. , 2007, The Journal of clinical investigation.

[37]  A. Pupi,et al.  Relationship between infarct size and severity measured by gated SPECT and long-term left ventricular remodelling after acute myocardial infarction , 2011, European Journal of Nuclear Medicine and Molecular Imaging.

[38]  Vincent Dor,et al.  The Endoventricular Circular Patch Plasty (“Dor Procedure”) in Ischemic Akinetic Dilated Ventricles , 2001, Heart Failure Reviews.

[39]  G. Krombach,et al.  Impact of infarct transmurality on layer-specific impairment of myocardial function: a myocardial deformation imaging study. , 2009, European heart journal.

[40]  Edward W Hsu,et al.  Magnetic resonance imaging-based finite element stress analysis after linear repair of left ventricular aneurysm. , 2008, The Journal of thoracic and cardiovascular surgery.

[41]  William Stewart,et al.  Recommendations for chamber quantification. , 2006, European journal of echocardiography : the journal of the Working Group on Echocardiography of the European Society of Cardiology.

[42]  K. McDonald,et al.  Length and PKA Dependence of Force Generation and Loaded Shortening in Porcine Cardiac Myocytes , 2012, Biochemistry research international.

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

[44]  C. Kramer,et al.  Mechanisms of Post-Infarct Left Ventricular Remodeling. , 2007, Drug discovery today. Disease mechanisms.