Theoretical Impact of the Injection of Material Into the Myocardium: A Finite Element Model Simulation

Background— To treat cardiac injuries created by myocardial infarcts, current approaches seek to add cells and/or synthetic extracellular matrices to the damaged ventricle to restore function. Because definitive myocardial regeneration remains undemonstrated, we propose that cardiac changes observed from implanted materials may result from altered mechanisms of the ventricle. Methods and Results— We exploited a validated finite element model of an ovine left ventricle with an anteroapical infarct to examine the short-term effect of injecting material to the left ventricular wall. The model's mesh and regional material properties were modified to simulate expected changes. Three sets of simulations were run: (1) single injection to the anterior border zone; (2) therapeutic multiple border zone injections; and (3) injection of material to the infarct region. Results indicate that additions to the border zone decrease end-systolic fiber stress proportionally to the fractional volume added, with stiffer materials improving this attenuation. As a potential therapy, small changes in wall volume (≈4.5%) reduce elevated border zone fiber stresses from mean end-systole levels of 28.2 kPa (control) to 23.3 kPa (treatment), similar to levels of 22.5 kPA computed in remote regions. In the infarct, injection improves ejection fraction and the stroke volume/end-diastolic volume relationship but has no effect on the stroke volume/end-diastolic pressure relationship. Conclusions— Simulations indicate that the addition of noncontractile material to a damaged left ventricular wall has important effects on cardiac mechanics, with potentially beneficial reduction of elevated myofiber stresses, as well as confounding changes to clinical left ventricular metrics.

[1]  Robert C Gorman,et al.  Border zone geometry increases wall stress after myocardial infarction: contrast echocardiographic assessment. , 2003, American journal of physiology. Heart and circulatory physiology.

[2]  J. Hubbell,et al.  Mechanical properties, proteolytic degradability and biological modifications affect angiogenic process extension into native and modified fibrin matrices in vitro. , 2005, Biomaterials.

[3]  D. Burkhoff,et al.  Heart reduction surgery: an analysis of the impact on cardiac function. , 1997, The Journal of thoracic and cardiovascular surgery.

[4]  A. McCulloch,et al.  Finite element stress analysis of left ventricular mechanics in the beating dog heart. , 1995, Journal of biomechanics.

[5]  R. Weisel,et al.  Improved heart function with myogenesis and angiogenesis after autologous porcine bone marrow stromal cell transplantation. , 2002, The Journal of thoracic and cardiovascular surgery.

[6]  P. Moghe,et al.  Mechanochemical manipulation of hepatocyte aggregation can selectively induce or repress liver-specific function. , 2000, Biotechnology and bioengineering.

[7]  J. Hubbell,et al.  Recombinant protein-co-PEG networks as cell-adhesive and proteolytically degradable hydrogel matrixes. Part I: Development and physicochemical characteristics. , 2005, Biomacromolecules.

[8]  A. Ganser,et al.  Intracoronary Bone Marrow Cell Transfer After Myocardial Infarction: Eighteen Months’ Follow-Up Data From the Randomized, Controlled BOOST (BOne marrOw transfer to enhance ST-elevation infarct regeneration) Trial , 2006, Circulation.

[9]  Theo Kofidis,et al.  Novel Injectable Bioartificial Tissue Facilitates Targeted, Less Invasive, Large-Scale Tissue Restoration on the Beating Heart After Myocardial Injury , 2005, Circulation.

[10]  P. Wernet,et al.  Repair of Infarcted Myocardium by Autologous Intracoronary Mononuclear Bone Marrow Cell Transplantation in Humans , 2002, Circulation.

[11]  M. Ratcliffe,et al.  The effect of ventricular volume reduction surgery in the dilated, poorly contractile left ventricle: a simple finite element analysis. , 1998, The Journal of thoracic and cardiovascular surgery.

[12]  Federica Limana,et al.  Mobilized bone marrow cells repair the infarcted heart, improving function and survival , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[13]  J. Ingwall,et al.  Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts , 2003, Nature Medicine.

[14]  Bernd Hertenstein,et al.  Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial , 2004, The Lancet.

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

[16]  Y. Yoon,et al.  Intramyocardial Transplantation of Autologous Endothelial Progenitor Cells for Therapeutic Neovascularization of Myocardial Ischemia , 2003, Circulation.

[17]  W Grossman,et al.  Wall stress and patterns of hypertrophy in the human left ventricle. , 1975, The Journal of clinical investigation.

[18]  Bjørn T. Stokke,et al.  Small-Angle X-ray Scattering and Rheological Characterization of Alginate Gels. 1. Ca-Alginate Gels , 2000 .

[19]  Randall J Lee,et al.  Fibrin glue alone and skeletal myoblasts in a fibrin scaffold preserve cardiac function after myocardial infarction. , 2004, Tissue engineering.

[20]  Doris A Taylor,et al.  Autologous skeletal myoblast transplantation improved hemodynamics and left ventricular function in chronic heart failure dogs. , 2005, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[21]  P J Hunter,et al.  A three-dimensional finite element method for large elastic deformations of ventricular myocardium: II--Prolate spheroidal coordinates. , 1996, Journal of biomechanical engineering.

[22]  F W Prinzen,et al.  Remodeling by ventricular pacing in hypertrophying dog hearts. , 2001, Cardiovascular research.

[23]  D. Glower,et al.  Cellular cardiomyoplasty improves diastolic properties of injured heart. , 1999, The Journal of surgical research.

[24]  R T Tranquillo,et al.  The fibroblast-populated collagen microsphere assay of cell traction force--Part 2: Measurement of the cell traction parameter. , 1995, Journal of biomechanical engineering.

[25]  W. Burghardt,et al.  Poly(N-isopropylacrylamide)-based semi-interpenetrating polymer networks for tissue engineering applications. Effects of linear poly(acrylic acid) chains on rheology , 2004, Journal of biomaterials science. Polymer edition.

[26]  N. Weissman,et al.  Transendocardial delivery of autologous bone marrow enhances collateral perfusion and regional function in pigs with chronic experimental myocardial ischemia. , 2001, Journal of the American College of Cardiology.

[27]  M. Moulton,et al.  Mechanical dysfunction in the border zone of an ovine model of left ventricular aneurysm. , 1995, The Annals of thoracic surgery.

[28]  K. Healy,et al.  Synthesis and characterization of injectable poly(N-isopropylacrylamide-co-acrylic acid) hydrogels with proteolytically degradable cross-links. , 2003, Biomacromolecules.