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International Journal for Multiscale Computational Engineering
IF: 1.016 5-Year IF: 1.194 SJR: 0.554 SNIP: 0.68 CiteScore™: 1.18

ISSN Print: 1543-1649
ISSN Online: 1940-4352

International Journal for Multiscale Computational Engineering

DOI: 10.1615/IntJMultCompEng.2011002352
pages 171-188

IN VITRO/IN SILICO CHARACTERIZATION OF ACTIVE AND PASSIVE STRESSES IN CARDIAC MUSCLE

Markus Boel
Department of Mechanical Engineering, TU Braunschweig, Germany
Oscar J. Abilez
Department of Surgery, Stanford University, Stanford, CA 94305
Ahmed N Assar
Department of Surgery, Stanford University, Stanford, CA 94305
Christopher K. Zarins
Department of Surgery, Stanford University, Stanford, CA 94305
Ellen Kuhl
Departments of Mechanical Engineering, Bioengineering, and Cardiothoracic, Surgery, Stanford University, USA

ABSTRACT

We propose a novel, robust, and easily reproducible, in vitro/in silico model system to characterize active and passive stresses in electroactive cardiac muscle using a hybrid experimental/computational approach. We explore active and passive stresses in healthy explanted heart slices in vitro, design a virtual test bed to simulate the in vitro measured stresses in silico, and predict altered active force generation in infarcted hearts in silico. For the in vitro model, explanted rat heart tissue slices are mounted on a force transducer and stimulated electrically through biphasic pulses. Isometric forces are recorded and translated into active circumferential stress. For the in silico model, stresses are additively decomposed into passive and active contributions, with the latter being related to the measured isometric force. A hierarchical finite element model for cardiac muscle tissue is developed based on passive tetrahedral unit cells, representing a network of interconnected polymeric chains, and active trusses, representing the contracting muscle fibers. First, we calibrate the model against our experiments with healthy explanted rat heart slices. Then, we predict acute and chronic alterations in active stress generation in infarcted hearts. We virtually explore isometric forces generation for different infarct area fractions and infarct locations. This approach has the potential to precisely quantify global loss of cardiac function for a given infarct area fraction.

REFERENCES

  1. Abilez, O., Benharash, P., Miyamoto, E., Gale, A., Xu, C., and Zarins, C.K., P19 progenitor cells progress to organized contracting myocytes after chemical and electrical stimulation: Implications for vascular tissue engineering. DOI: 10.1583/06-1844.1

  2. Abilez, O., Benharash, P., Mehrotra, M., Miyamoto, E., Gale, A., Picquet, J., Xu, C., and Zarins, C., A novel culture system shows that stem cells can be grown in 3D and under physiologic pulsatile conditions for tissue engineering of vascular grafts. DOI: 10.1016/j.jss.2006.02.017

  3. Abilez, O. J., Wong, J., Prakash, R., Deisseroth, K., Zarins, C. K., and Kuhl, E., Multiscale computational models for optogenetic control of cardiac function. DOI: 10.1016/j.bpj.2011.08.004

  4. Allen, D. G., Jewell, B. R., and Murray, J. W., The contribution of activation processes to the length-tension relation of cardiac muscle. DOI: 10.1038/248606a0

  5. Berne, R. M. and Levy, M. N., Cardiovascular Physiology.

  6. Bers, D. M., Excitation-Contraction Coupling and Cardiac Contractile Force.

  7. Böl, M. and Reese, S., Finite element modelling of rubber-like polymers based on chain statistics. DOI: 10.1016/j.ijsolstr.2005.06.086

  8. Böl, M. and Reese, S., A new approach for the simulation of skeletal muscles using the tool of statistical mechanics. DOI: 10.1002/mawe.200700225

  9. Böl, M. and Reese, S., Micromechanical modelling of skeletal muscles based on the finite element method. DOI: 10.1080/10255840701771750

  10. Böl, M., Reese, S., Parker, K. K., and Kuhl, E., Computational modeling of muscular thin film for cardiac repair. DOI: 10.1007/s00466-008-0328-5

  11. Böl, M., Micromechanical modelling of skeletal muscles: From the single fibre to the whole muscle. DOI: 10.1007/s00419-009-0378-y

  12. Brooks, W. W. and Conrad, C. H., Differences between mouse and rat myocardial contractile responsiveness to calcium. DOI: 10.1016/S1095-6433(99)00099-9

  13. Bustamante, C., Marko, J. F., Siggia, E. D., and Smith, S., Entropic elasticity of lambda-phage DNA. DOI: 10.1126/science.8079175

  14. Capasso, J. M., Malhotra, A., Scheuer, J., and Sonnenblick, E. H., Myocardial biochemical, contractile, and electrical performance after imposition of hypertension in young and old rats. DOI: 10.1161/01.RES.58.4.445

  15. Costa, K. D., Holmes, J. W., and McCulloch, A. D., Modelling cardiac mechanical properties in three dimensions. DOI: 10.1098/rsta.2001.0828

  16. Dokos, S., Smaill, B. H., Young, A. A., and LeGrice, I. J., Shear properties of passive ventricular myocardium. DOI: 10.1152/ajpheart.00111.2002

  17. Ehret, A. E. and Itskov, M., Modeling of anisotropic softening phenomena: Application to soft biological tissues. DOI: 10.1016/j.ijplas.2008.06.001

  18. Flory, P. J., Statistical Mechanics of Chain Molecules.

  19. Ganong, W. F., Review of Medical Physiology.

  20. Gandolfi, A. J., Brendel, K., Fisher, R. L., and Michaud, J. P., Use of tissue slices in chemical mixture toxicology and interspecies investigations. DOI: 10.1016/0300-483X(95)03224-4

  21. Göktepe, S. and Kuhl, E., Computational modeling of electrophysiology: A novel finite element approach. DOI: 10.1002/nme.2571

  22. Göktepe, S. and Kuhl, E., Electromechanics of the heart–A unified approach to the strongly coupled excitation-contraction problem. DOI: 10.1007/s00466-009-0434-z

  23. Göktepe, S., Acharya, S. N. S., Wong, J., and Kuhl, E.,, Computational modeling of passive myocardium. DOI: 10.1002/cnm.1402

  24. Göktepe, S., Abilez, O. J., and Kuhl, E., A generic approach towards finite growth with examples of athlete's heart, cardiac dilation, and cardiac wall thickening. DOI: 10.1016/j.jmps.2010.07.003

  25. Göktepe, S., Abilez, O. J., Parker, K. K., and Kuhl, E., A multiscale model for eccentric and concentric cardiac growth through sarcomerogenesis. DOI: 10.1016/j.jtbi.2010.04.023

  26. Gordon, A. M., Huxley, A. F., and Julian, F. J., The variation in isometric tension with sarcomere length in vertebrate muscle fibre.

  27. Habeler, W., Pouillot, S., Plancheron, A., Puceat, M., Peschanski, M., and Monville, C., An in vitro beating heart model for long-term assessment of experimental therapeutics. DOI: 10.1093/cvr/cvn299

  28. Halbach, M., Pillekamp, F., Brockmeier, K., Hescheler, J., Muller-Ehmsen, J., and Reppel, M., Ventricular slices of adult mouse hearts—A new multicellular in vitro model for electrophysiological studies. DOI: 10.1159/000095132

  29. Holzapfel, G. A. and Ogden, R. W., Constitutive modelling of passive myocardium. A structurally-based framework for material characterization. DOI: 10.1098/rsta.2009.0091

  30. Hunter, P. J., McCulloch, A. D., and ter Keurs, H. E., Modelling the mechanical properties of cardiac muscle. DOI: 10.1016/S0079-6107(98)00013-3

  31. Huxley, H. and Hanson, J., Changes in the cross-striations of muscle during contraction and stretch and their structural interpretation. DOI: 10.1038/173973a0

  32. Itoh, A., Krishnamurthy, G., Swanson, J., Ennis, D., Bothe, W., Kuhl, E., Karlsson, M., Davis, L., Miller, D.C., and Ingels, N. B., Active stiffening of mitral valve leaflets in the beating heart. DOI: 10.1152/ajpheart.00120.2009

  33. Kotikanyadanam, M., Göktepe, S., and Kuhl, E., Computational modeling of electrocardiograms — A finite element approach towards cardiac excitation. DOI: 10.1002/cnm.1273

  34. Kratky, O. and Porod, G., Röntgenuntersuchung gelöster Fadenmoleküle. DOI: 10.1002/recl.19490681203

  35. Kuhl, E., Garikipati, K., Arruda, E. M., and Grosh, K., Remodeling of biological tissue—Mechanically induced reorientation of a transversely isotropic chain network. DOI: 10.1016/j.jmps.2005.03.002

  36. Kuhl, E., Menzel, A., and Garikipati, K., On the convexity of transversely isotropic chain network models. DOI: 10.1080/14786430500080296

  37. Kuhl, E. and Holzapfel, G. A., A continuum model for remodeling in living structures. DOI: 10.1007/s10853-007-1917-y

  38. Kumar, V., Abbas, A. K., and Fausto, N., Robbins and Cotran Pathologic Basis of Disease.

  39. Mulieri, L. A., Hasenfuss, G., Ittleman, F., Blanchard, E. M., and Alpert, N. R., Protection of human left ventricular myocardium from cutting injury with 2.3/butanedione monoxime. DOI: 10.1161/01.RES.65.5.1441

  40. Omens, J. H., MacKenna, D. A., and McCulloch, A. D., Measurements of strain and analysis of stress in resting rat left ventricular myocardium. DOI: 10.1016/0021-9290(93)90030-I

  41. Opie, L. H., Heart Physiology: From Cell to Circulation.

  42. Pillekamp, F., Reppel, M., Dinkelacker, V., Duan, Y., Jazmati, N., Bloch, W., Brockmeier, K., Hescheler, J., Fleischmann, B. K., and Koehling, R., Establishment and characterization of a mouse embryonic heart slice preparation. DOI: 10.1016/j.jelectrocard.2005.06.048

  43. Pillekamp, F., Reppel, M., Rubenchyk, O., Pfannkuche, K., Matzkies, M., Bloch, W., Sreeram, N., Brockmeier, K., and Hescheler, J., Force measurements of human embryonic stem cell-derived cardiomyocytes in an in vitro transplantation model. DOI: 10.1634/stemcells.2006-0094

  44. Pillekamp, F., Halbach, M., Reppel, M., Rubenchyk, O., Pfannkuche, K., Xi, J. Y., Bloch, W., Sreeram, N., Brockmeier, K., and Hescheler, J., Neonatal murine heart slices. A robust model to study ventricular isometric contractions. DOI: 10.1159/000110443

  45. Pollack, G. H. and Huntsman, L. L., Sarcomere length-active force relation in living mammalian cardiac muscle.

  46. Schmid, H., Nash, M. P., Young, A. A., and Hunter, P. J., Myocardial material parameter estimation—A comparative study for simple shear. DOI: 10.1115/1.2244576

  47. Schmid, H., O'Callaghan, P., Nash, M. P., Lin, W., LeGrice, I. J., Smaill, B. H., Young, A. A., and Hunter, P. J., Myocardial material parameter estimation–A non-homogeneous finite element study from simple shear tests. DOI: 10.1007/s10237-007-0083-0

  48. Schmid, H., Wang, Y. K., Ashton, J., Ehret, A. E., Krittian, S. B. S., Nash, M. P., and Hunter, P. J., Myocardial material parameter estimation—A comparison of invariant based orthotropic constitutive equations. DOI: 10.1080/10255840802459420

  49. Siebert, T., Rode, C., Herzog, W., Till, O., and Blickhan, R., Nonlinearities make a difference: Comparison of two common Hill-type models with real muscle. DOI: 10.1007/s00422-007-0197-6

  50. Treloar, L. R. G., The Physics of Rubber Elasticity.

  51. Tsamis, A., Bothe, W., Kvitting, J. P., Swanson, J. C., Miller, D. C., and Kuhl, E., Active contraction of cardiac muscle: In vivo characterization of mechanical activation sequences in the beating heart. DOI: 10.1016/j.jmbbm.2011.03.027

  52. Wall, S. T., Walker, J. C., Healy, K. E., Ratcliffe, M. B., and Guccione, J. M., Theoretical impact of the injection of material into the myocardium: A finite element model simulation. DOI: 10.1161/CIRCULATIONAHA.106.657270

  53. Wollert, K. C., Meyer, G. P., Lotz, J., Ringes-Lichtenberg, S., Lippolt, P., Breidenbach, C., Fichtner, S., Korte, T., Hornig, B., Messinger, D., Arseniev, L., Hertenstein, B., Ganser, A., and Drexler, H., Intracoronary autologous bone-marrow cell transfer after myocardial infarction: The BOOST randomised controlled clinical trial. DOI: 10.1016/S0140-6736(04)16626-9

  54. Zimmermann, W. H., Didié, M., Döker, S., Melnychenko, I., Naito, H., Rogge, C., Tiburcy, M., and Eschenhagen, T., Heart muscle engineering: An update on cardiac muscle replacement therapy. DOI: 10.1016/j.cardiores.2006.03.023


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