The Mechanical Characterisation of Bovine Embolus Analogues Under Various Loading Conditions

Abstract

Embolus Analogues (EAs) can provide understanding of the mechanical characteristics of blood clots of cardiac origin. Bovine EAs (n = 29) were fabricated with varying concentrations of thrombin (0–20 NIHU/ml blood). Histological staining confirmed that EA composition compared sufficiently with human samples reported in literature. EAs were mechanically described under seven testing conditions: tensile, compression, shear wave ultrasound elastography (SWE), parallel plate rheometry, indentation, creep and relaxation. The Young modulus of bovine EAs in tension varied from 7 kPa (5% strain) to 84 kPa (50% strain). The compressive Young modulus increased with increasing thrombin concentration, which was in agreement with the SWE results. There was no significant difference in Young modulus throughout the clot (p < 0.05). The EAs displayed a non-linear response under parallel plate rheometry, creep and stress relaxation. The 3rd order Mooney–Rivlin constitutive equation and Standard Linear Solid model were used to fit the non-linear stress–strain response and time-dependent properties, respectively. This is the first study in which bovine EAs, with and without addition of thrombin, are histologically and mechanically described with corresponding proposed constitutive equations. The equations and experimental data determined can be applied for future numerical and experimental testing of mammalian EAs and cardiac source clots.

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References

  1. 1.

    Beldi, G., L. Beng, G. Siegel, S. Bisch-Knaden, and D. Candinas. Prevention of perioperative thromboembolism in patients with atrial fibrillation. Br. J. Surg. Nov. 94(11):1351–1355, 2007.

    Article  Google Scholar 

  2. 2.

    Bernal, M., F. Chammings, M. Couade, J. Bercoff, M. Tanter, and J. L. Gennisson. In vivo quantification of the nonlinear shear modulus in breast lesions: feasibility study. IEEE Trans. Ultrason. Ferroelectr. Frequ. Control 63(1):101–109, 2016.

    Article  Google Scholar 

  3. 3.

    Brophy, D. F., R. J. Martin, T. W. Gehr, and M. E. Carr. A hypothesis-generating study to evaluate platelet activity in diabetics with chronic kidney disease. Thromb. J. 3(1):3, 2005.

    Article  Google Scholar 

  4. 4.

    Campbell, W. B., B. M. Ridler, and T. H. Szymanska. Two-year follow-up after acute thromboembolic limb ischaemia: the importance of anticoagulation. Eur. J. Vasc. Endovasc. Surg. 19:169–173, 2000.

    Article  Google Scholar 

  5. 5.

    Carr, M. E., A. Krishnaswami, and E. J. Martin. Platelet contractile force (PCF) and clot elastic modulus (CEM) are elevated in diabetic patients with chest pain. Diabet. Med. 19(10):862–866, 2002.

    Article  Google Scholar 

  6. 6.

    Chueh, J. K., A. K. Wakhloo, G. H. Hendricks, C. F. Silva, J. P. Weaver, and M. J. Gounis. Mechanical characterisation of Thromboemboli in acute ischemic stroke and Laboratory Embolus Analogues. Am. J. Neuroradiol. 32:1237–1244, 2011.

    Article  Google Scholar 

  7. 7.

    Davie, E. W., and K. Fujikawa. Basic mechanisms in blood coagulation. Annu. Rev. Biochem. 44:799–829, 1975.

    Article  Google Scholar 

  8. 8.

    Dempfle, C. E., T. Kalsch, E. Elmas, N. Suvajac, T. Luecke, E. Muench, and M. Borggrefe. Impact of fibrinogen concentration in severely ill patients on mechanical properties of whole blood clots. Blood Coagul Fibrinolysis 19:765–770, 2008.

    Article  Google Scholar 

  9. 9.

    Eggebrecht, H., A. Schmermund, T. Voigtländer, P. Kahlert, R. Erbel, and R. H. Mehta. Risk of stroke after transcatheter aortic valve implantation (TAVI): a meta-analysis of 10,037 published patients. EuroIntervention 8:129–138, 2012.

    Article  Google Scholar 

  10. 10.

    Fuster, V., L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J. Y. Le Heuzey, G. N. Kay, J. E. Lowe, S. B. Olsson, E. N. Prystowsky, J. L. Tamargo, S. Wann, S. C. Smith, Jr, A. K. Jacobs, C. D. Adams, J. L. Anderson, E. M. Antman, J. L. Halperin, S. A. Hunt, R. Nishimura, J. P. Ornato, R. L. Page, B. Riegel, S. G. Priori, J. J. Blanc, A. Budaj, A. J. Camm, V. Dean, J. W. Deckers, C. Despres, K. Dickstein, J. Lekakis, K. McGregor, M. Metra, J. Morais, A. Osterspey, J. L. Tamargo, and J. L. Zamorano. Guidelines for the management of patients with atrial fibrillation. Circulation 114:257–354, 2006.

    Article  Google Scholar 

  11. 11.

    Gennisson, J. L., M. Renier, S. Catheline, C. Barriere, J. Bercoff, M. Tanter, and M. Fink. Acoustoelasticity in soft solds: assessment of the non-linear shear modulus with acoustic radiation force. J. Acoust. Soc. Am. 122(6):3211–3219, 2007.

    Article  Google Scholar 

  12. 12.

    Gralla, J., G. Schroth, L. Remonda, A. Fleischmann, J. Fandino, J. Slotboom, and C. Brekenfeld. A dedicated animal model for mechanical thrombectomy in acute Stroke. AJNR 27:1357–1361, 2006.

    Google Scholar 

  13. 13.

    Heeringa, J., D. A. van der Kuip, A. Hofman, J. A. Kors, G. van Herpen, B. H. Stricker, T. Stijnen, G. Y. Lip, and J. C. Witteman. Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam study. Eur. Heart. J. 27:949–953, 2006.

    Article  Google Scholar 

  14. 14.

    Isogai, Y., A. Iida, I. Chikatsu, K. Mochizuki, and M. Abe. Dynamic viscoelasticity of blood during clotting in health and disease. Biorheology 10(3):411–424, 1973.

    Article  Google Scholar 

  15. 15.

    Jiang, Y., L. Guoyang, L. X. Qian, S. Liang, M. Destrade, and Y. Cao. Measuring the linear and non linear elastic properties of brain tissue with shear waves and inverse analysis. Biomech. Model Mechanobiol. 14:1119–1128, 2014.

    Article  Google Scholar 

  16. 16.

    Juliano, T. F., A. M. Forster, P. L. Drzal, T. Weerasooriya, P. Moy, and M. R. VanLandingham. Multiscale mechanical characterization of biomimetic physically associating gels. J. Mater. Res. 21(8):2084–2092, 2006.

    Article  Google Scholar 

  17. 17.

    Kan, I., I. Yuki, Y. Murayama, F. A. Vinuela, R. H. Kim, H. V. Vinters, and F. Vinuela. A novel method of thrombus preparation for use in a swine model for evaluation of thrombectomy devices. AJNR 31:1741–1743, 2010.

    Article  Google Scholar 

  18. 18.

    Kannel, W. B., and E. J. Benjamin. Status of the epidemiology of atrial fibrillation. Med. Clin. N. Am. 92:17–40, 2008.

    Article  Google Scholar 

  19. 19.

    Kay, R., J. Woo, L. Kreel, H. Y. Wong, R. Teoh, and M. G. Nicholls. Stroke subtypes among Chinese living in Hong Kong: the Shatin Stroke Registry. Neurology. 42:985–987, 1992.

    Article  Google Scholar 

  20. 20.

    Kline, J. A., and R. S. Runyon. Pulmonary embolism and deep vein thrombosis. In: Emergency Medicine Concepts and Clinical Practice7th, edited by J. A. Marx, R. S. Hockberger, and R. M. Walls. New York: Elsevier, 2010, pp. 1157–1169.

    Google Scholar 

  21. 21.

    Krasokha, N., W. Theisen, S. Reese, P. Mordasini, C. Brekenfeld, J. Gralla, J. Slotboom, G. Schrott, and H. Monstadt. Mechanical properties of blood clots—a new test method. Mat wiss u Werkstofftech. 41:1019–1024, 2010.

    Article  Google Scholar 

  22. 22.

    Lalley, C., A. J. Reid, and P. J. Prendergast. Elastic behaviour of porcine coronary artery tissue under uniaxial and equibiaxial tension. Ann. Biomed. Eng. 32(10):1355–1364, 2004.

    Article  Google Scholar 

  23. 23.

    Maier, A., M. W. Gee, C. Reeps, H.-H. Eckstein, and W. A. Wall. Impact of calcifications on patient-specific wall stress analysis of abdominal aortic aneurysms. Biomech. Model. Mechanobiol. 9:511–521, 2010.

    Article  Google Scholar 

  24. 24.

    Menke, J., L. Lüthje, A. Kastrup, and J. Larsen. Thromboembolism in atrial fibrillation. Am. J. Cardiol. 105:502–510, 2010.

    Article  Google Scholar 

  25. 25.

    Prystowsky, E. N. The history of atrial fibrillation: the last 100 years. J. Cardiovasc. Electrophysiol. 19:575–582, 2008.

    Article  Google Scholar 

  26. 26.

    Robinson, R. A., L. H. Herbertson, S. Sarkar Das, R. A. Malinauskas, W. F. Pritchard, and L. W. Grossman. Limitations of using synthetic blood clots for measuring in vitro clot capture efficiency of inferior vena cava filters. Med. Dev. (Auckland, N.Z.) 6:49–57, 2013.

    Google Scholar 

  27. 27.

    Schmitt, C., A. H. Henni, and G. Cloutier. Characterization of blood clot viscoelasticity by dynamic ultrasound elastography and modeling of the rheological behaviour. J. Biomech. 44:622–629, 2011.

    Article  Google Scholar 

  28. 28.

    Sigrist, R. M. S., J. Liau, A. El Kaffas, M. C. Chammas, and J. K. Willmann. Ultrasound elastography: reviwe of techniques and clinical applications. Theranostics 7(5):1303, 2017.

    Article  Google Scholar 

  29. 29.

    Whitbourne, P. G. S. Changes in the Clotting Viscoelasticity Caused by Cardiopulmonary Bypass (CPB) Surgery [dissertation]. MA: Cambridge Massachusetts Institute of Technology, 1998.

    Google Scholar 

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Funding

Galway Mayo Institute of Technology 40th Anniversary Seed Funding.

Conflict of Interest

All authors declare that they have no conflicts of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. Burkes Ltd., is an EU approved abattoir. This article does not contain any studies with human participants performed by any of the authors.

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Correspondence to L. Morris.

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Associate Editors Ulrich Steinseifer and Ajit P. Yoganathan oversaw the review of this article.

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Cite this article

Malone, F., McCarthy, E., Delassus, P. et al. The Mechanical Characterisation of Bovine Embolus Analogues Under Various Loading Conditions. Cardiovasc Eng Tech 9, 489–502 (2018). https://doi.org/10.1007/s13239-018-0352-3

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Keywords

  • Embolus analogues
  • Mechanical testing
  • Blood clots
  • Cardiac source clots
  • Constitutive equations