Computational predictions of improved of wall mechanics and function of the infarcted left ventricle at early and late remodelling stages: comparison of layered and bulk hydrogel injectates

  • Kortsmit, Jeroen (Cardiovascular Research Unit, Chris Barnard Division of Cardiothoracic Surgery, University of Cape Town) ;
  • Davies, Neil H. (Cardiovascular Research Unit, Chris Barnard Division of Cardiothoracic Surgery, University of Cape Town) ;
  • Miller, Renee (Cardiovascular Research Unit, Chris Barnard Division of Cardiothoracic Surgery, University of Cape Town) ;
  • Zilla, Peter (Cardiovascular Research Unit, Chris Barnard Division of Cardiothoracic Surgery, University of Cape Town) ;
  • Franz, Thomas (Cardiovascular Research Unit, Chris Barnard Division of Cardiothoracic Surgery, University of Cape Town)
  • 투고 : 2013.03.07
  • 심사 : 2013.06.07
  • 발행 : 2013.03.25


Acellular intra-myocardial biomaterial injections have been shown to be therapeutically beneficial in inhibiting ventricular remodelling of myocardial infarction (MI). Based on a biventricular canine cardiac geometry, various finite element models were developed that comprised an ischemic (II) or scarred infarct (SDI) in left ventricular (LV) antero-apical region, without and with intra-myocardial biomaterial injectate in layered (L) and bulk (B) distribution. Changes in myocardial properties and LV geometry were implemented corresponding to infarct stage (tissue softening vs. stiffening, infarct thinning, and cavity dilation) and injectate (infarct thickening). The layered and bulk injectate increased ejection fraction of the infarcted LV by 77% (II+L) and 25% (II+B) at the ischemic stage and by 61% (SDI+L) and 63% (SDI+B) at the remodelling stage. The injectates decreased the mean end-systolic myofibre stress in the infarct by 99% (II+L), 97% (II+B), 70% (SDI+L) and 36% (SDI+B). The bulk injectate was slightly more effective in improving LV function at the remodelling stage whereas the layered injectate was superior in functional improvement at ischemic stage and in reduction of wall stress at ischemic and remodelling stage. These findings may stimulate and guide further research towards tailoring acellular biomaterial injectate therapies for MI.



  1. Baig, M.K., Mahon, N., McKenna, W.J., Caforio, A.L.P., Bonow, R.O. and Francis, G.S. (1999), "The pathophysiology of advanced heart failure", Heart Lung, 28(2), 87-101.
  2. Beg, M.F., Helm, P.A., McVeigh, E., Miller, M.I. and Winslow, R.L. (2004), "Computational cardiac anatomy using mri", Magn. Reson. Med. 52(5), 1167-1174.
  3. Bogen, D.K., Rabinowitz, S.A., Needleman, A., McMahon, T.A. and Abelmann, W.H. (1980), "An analysis of the mechanical disadvantage of myocardial infarction in the canine left ventricle" Circ. Res. 47(5), 728-741.
  4. Christman, K.L., Vardanian, A.J., Fang, Q., Sievers, R.E., Fok, H.H. and Lee, R.J. (2004), "Injectable fibrin scaffold improves cell transplant survival, reduces infarct expansion, and induces neovasculature formation in ischemic myocardium" J. Am. Coll. Cardiol. 44(3), 654-660.
  5. Dai, W., Wold, L.E., Dow, J.S. and Kloner, R.A. (2005), "Thickening of the infarcted wall by collagen injection improves left ventricular function in rats: A novel approach to preserve cardiac function after myocardial infarction" J. Am. Coll. Cardiol. 46(4), 714-719.
  6. Dang, A.B.C., Guccione, J.M., Mishell, J.M., Zhang, P., Wallace, A.W., Gorman, R.C., Gorman, J.H. and Ratcliffe, M.B. (2004), "Akinetic segments of myocardial infarction contain contracting. Myocytes: A finite element model study" J. Am. Coll. Cardiol. 43(5), 177a.
  7. Dang, A.B.C., Guccione, J.M., Mishell, J.M., Zhang, P., Wallace, A.W., Gorman, R.C., Gorman, J.H. and Ratcliffe, M.B. (2005), "Akinetic myocardial infarcts must contain contracting myocytes: Finite-element model study" Am J Physiol-Heart C 288(4), H1844-H1850.
  8. Dobner, S., Bezuidenhout, D., Govender, P., Zilla, P. and Davies, N. (2009), "A synthetic non-degradable polyethylene glycol hydrogel retards adverse post-infarct left ventricular remodeling" J. Card. Fail. 15(7), 629-636.
  9. Doll, S. and Schweizerhof, K. (2000), "On the development of volumetric strain energy functions" Journal of Applied Mechanics-Transactions of the Asme 67(1), 17-21.
  10. Guccione, J.M. and McCulloch, A.D. (1993), "Mechanics of active contraction in cardiac-muscle .1. Constitutive relations for fiber stress that describe deactivation" J. Biomech. Eng. 115(1), 72-81.
  11. Guccione, J.M., McCulloch, A.D. and Waldman, L.K. (1991), "Passive material properties of intact ventricular myocardium determined from a cylindrical model" J. Biomech. Eng. 113(1), 42-55.
  12. Guccione, J.M., Moonly, S.M., Moustakidis, P., Costa, K.D., Moulton, M.J., Ratcliffe, M.B. and Pasque, M.K. (2001), "Mechanism underlying mechanical dysfunction in the border zone of left ventricular aneurysm: A finite element model study" Ann. Thorac. Surg. 71(2), 654-662.
  13. Holmes, J.W., Borg, T.K. and Covell, J.W. (2005), "Structure and mechanics of healing myocardial infarcts" Annu Rev Biomed Eng 7(-), 223-253.
  14. Ifkovits, J.L., Tous, E., Minakawa, M., Morita, M., Robb, J.D., Koomalsingh, K.J., Gorman, J.H., Gorman, R.C. and Burdick, J.A. (2010), "Injectable hydrogel properties influence infarct expansion and extent of postinfarction left ventricular remodeling in an ovine model" P Natl Acad Sci USA 107(25), 11507-11512.
  15. Kadner, K., Dobner, S., Franz, T., Bezuidenhout, D., Sirry, M.S., Zilla, P. and Davies, N.H. (2012), "The beneficial effects of deferred delivery on the efficiency of hydrogel therapy post myocardial infarction" Biomaterials 33(7), 2060-2066.
  16. Katz, A.M. (2008), "The "modern" view of heart failure: How did we get here?" Circ. Heart Fail. 1(1), 63-71.
  17. Kerckhoffs, R., Neal, M., Gu, Q., Bassingthwaighte, J., Omens, J. and McCulloch, A. (2007), "Coupling of a 3D finite element model of cardiac ventricular mechanics to lumped systems models of the systemic and pulmonic circulation" Ann. Biomed. Eng. 35(1), 1-18.
  18. Kortsmit, J., Davies, N.H., Miller, R., Macadangdang, J.R., Zilla, P. and Franz, T. (2012), "The effect of hydrogel injection on cardiac function and myocardial mechanics in a computational post-infarction model" Comput. Methods Biomech. Biomed. Engin. e-pub(-), -.
  19. Laird, J.D. and Vellekoop, H.P. (1977), "The course of passive elasticity of myocardial tissue following experimental infarction in rabbits and its relation to mechanical dysfunction" Circ. Res. 41(5), 715-721.
  20. Landa, N., Miller, L., Feinberg, M.S., Holbova, R., Shachar, M., Freeman, I., Cohen, S. and Leor, J. (2008), "Effect of injectable alginate implant on cardiac remodeling and function after recent and old infarcts in rat" Circulation 117(11), 1388-1396.
  21. Mendis, S., Puska, P. and Norrving, B. (2011), Global atlas on cardiovascular disease prevention and control: Policies, strategies and interventions. World Health Organisation, Geneva.
  22. Morita, M., Eckert, C.E., Matsuzaki, K., Noma, M., Ryan, L.P., Burdick, J.A., Jackson, B.M., Gorman Iii, J.H., Sacks, M.S. and Gorman, R.C. (2011), "Modification of infarct material properties limits adverse ventricular remodeling" Ann. Thorac. Surg. 92(2), 617-624.
  23. Moustakidis, P., Maniar, H.S., Cupps, B.P., Absi, T., Zheng, J., Guccione, J.M., Sundt, T.M. and Pasque, M.K. (2002), "Altered left ventricular geometry changes the border zone temporal distribution of stress in an experimental model of left ventricular aneurysm: A finite element model study" Circulation 106(13 Supplement), I-168-175.
  24. Nelson, D.M., Ma, Z., Fujimoto, K.L., Hashizume, R. and Wagner, W.R. (2011), "Intra-myocardial biomaterial injection therapy in the treatment of heart failure: Materials, outcomes and challenges" Acta Biomater. 7(1), 1-15.
  25. Nielsen, P.M., Le Grice, I.J., Smaill, B.H. and Hunter, P.J. (1991), "Mathematical model of geometry and fibrous structure of the heart" Am. J. Physiol. Heart Circ. Physiol. 260(4), H1365-H1378.
  26. Opie, L.H., Commerford, P.J., Gersh, B.J. and Pfeffer, M.A. (2006), "Controversies in ventricular remodelling" Lancet 367(9507), 356-367.
  27. Pfeffer, M. and Braunwald, E. (1990), "Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications" Circulation 81(4), 1161-1172.
  28. Pilla, J.J., Gorman III, J.H. and Gorman, R.C. (2009), "Theoretic impact of infarct compliance on left ventricular function" Ann. Thorac. Surg. 87(3), 803-810.
  29. Sam, F., Sawyer, D.B., Chang, D.L., Eberli, F.R., Ngoy, S., Jain, M., Amin, J., Apstein, C.S. and Colucci, W.S. (2000), "Progressive left ventricular remodeling and apoptosis late after myocardial infarction in mouse heart" Am. J. Physiol. Heart Circ. Physiol. 279(1), H422-428.
  30. Smith, M., Russell, R.O., Jr., Feild, B.J. and Rackley, C.E. (1974), "Left ventricular compliance and abnormally contracting segments in postmyocardial infarction patients" Chest 65(4), 368-378.
  31. Sun, K., Stander, N., Jhun, C.S., Zhang, Z.H., Suzuki, T., Wang, G.Y., Saeed, M., Wallace, A.W., Tseng, E.E., Baker, A.J., Saloner, D., Einstein, D.R., Ratcliffe, M.B. and Guccione, J.M. (2009), "A computationally efficient formal optimization of regional myocardial contractility in a sheep with left ventricular aneurysm" J. Biomech. Eng. 131(11), 111001.
  32. Sutton, M.G. and Sharpe, N. (2000), "Left ventricular remodeling after myocardial infarction: Pathophysiology and therapy" Circulation 101(25), 2981-2988.
  33. Tous, E., Ifkovits, J.L., Koomalsingh, K.J., Shuto, T., Soeda, T., Kondo, N., Gorman, J.H., 3rd, Gorman, R.C. and Burdick, J.A. (2011), "Influence of injectable hyaluronic acid hydrogel degradation behavior on infarction-induced ventricular remodeling" Biomacromolecules 12(11), 4127-4135.
  34. Walker, J.C., Ratcliffe, M.B., Zhang, P., Wallace, A.W., Fata, B., Hsu, E.W., Saloner, D. and Guccione, J.M. (2005), "Mri-based finite-element analysis of left ventricular aneurysm" Am. J. Physiol. Heart Circ. Physiol. 289(2), H692-700.
  35. Wall, S.T., Walker, J.C., Healy, K.E., Ratcliffe, M.B. and Guccione, J.M. (2006), "Theoretical impact of the injection of material into the myocardium: A finite element model simulation" Circulation 114(24), 2627-2635.
  36. Wenk, J.F., Eslami, P., Zhang, Z., Xu, C., Kuhl, E., Gorman Iii, J.H., Robb, J.D., Ratcliffe, M.B., Gorman, R.C. and Guccione, J.M. (2011), "A novel method for quantifying the in-vivo mechanical effect of material injected into a myocardial infarction" Ann. Thorac. Surg. 92(3), 935-941.
  37. Wenk, J.F., Wall, S.T., Peterson, R.C., Helgerson, S.L., Sabbah, H.N., Burger, M., Stander, N., Ratcliffe, M.B. and Guccione, J.M. (2009), "A method for automatically optimizing medical devices for treating heart failure: Designing polymeric injection patterns" J. Biomech. Eng. 131(12), 121011.

피인용 문헌

  1. Personalised computational cardiology: Patient-specific modelling in cardiac mechanics and biomaterial injection therapies for myocardial infarction vol.21, pp.6, 2016,
  2. Fibrotic infarction on the LV free wall may alter the mechanics of healthy septal wall during passive filling vol.28, pp.6, 2017,
  3. A Preliminary Computational Investigation Into the Flow of PEG in Rat Myocardial Tissue for Regenerative Therapy vol.6, pp.None, 2014,