Annals of Biomedical Engineering

, Volume 33, Issue 12, pp 1808–1818 | Cite as

A New Biomechanical Perfusion System for ex vivo Study of Small Biological Intact Vessels

  • Niklas Bergh
  • Mikael Ekman
  • Erik Ulfhammer
  • Maria Andersson
  • Lena Karlsson
  • Sverker Jern
Article

Abstract

The vascular endothelium transduces physical stimuli within the circulation into physiological responses, which influence vascular remodelling and tissue homeostasis. Therefore, a new computerized biomechanical ex vivo perfusion system was developed, in which small intact vessels can be perfused under well-defined biomechanical forces. The system enables monitoring and regulation of vessel lumen diameter, shear stress, mean pressure, variable pulsatile pressure and flow profile, and diastolic reversal flow. Vessel lumen measuring technique is based on detection of the amount of flourescein over a vessel segment. A combination of flow resistances, on/off switches, and capacitances creates a wide range of pulsatile pressures and flow profiles. Accuracy of the diameter measurement was evaluated. The diameters of umbilical arteries were measured and compared with direct ultrasonographic measurement of the vessel diameter. As part of the validation the pulsatile pressure waveform was altered, e.g., in terms of pulse pressure, frequency, diastolic shape, and diastolic reversal flow. In a series of simulation experiments, the hemodynamic homeostasis functions of the system were successfully challenged by generating a wide range of vascular diameters in artificial and intact human vessels. We conclude that the system presented may serve as a methodological and technical platform when performing advanced hemodynamic stimulation protocols.

Keywords

Biomechanical forces Shear stress Pulsatile pressure Perfusion system ex vivo 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Bakker, E. N., E. T. van Der Meulen, J. A. Spaan, and E. VanBavel. Organoid culture of cannulated rat resistance arteries: Effect of serum factors on vasoactivity and remodeling. Am. J. Physiol. Heart Circ. Physiol. 278:H1233–H1240, 2000.Google Scholar
  2. 2.
    Bao, X., C. Lu, and J. A. Frangos. Temporal gradient in shear but not steady shear stress induces PDGF-A and MCP-1 expression in endothelial cells: Role of NO, NF, ΚB, and egr-1. Arterioscler. Thromb. Vasc. Biol. 19:996–1003, 1999.Google Scholar
  3. 3.
    Bardy, N., G. J. Karillon, R. Merval, J. L. Samuel, and A. Tedgui. Differential effects of pressure and flow on DNA and protein synthesis and on fibronectin expression by arteries in a novel organ culture system. Circ. Res. 77:684–694, 1995.Google Scholar
  4. 4.
    Benbrahim, A., G. J. L'Italien, B. B. Milinazzo, D. F. Warnock, S. Dhara, J. P. Gertler, R. W. Orkin, and W. M. Abbott. A compliant tubular device to study the influences of wall strain and fluid shear stress on cells of the vascular wall. J. Vasc. Surg. 20:184–194, 1994.Google Scholar
  5. 5.
    Blackman, B. R., G. Garcia-Cardena, and M. A. Gimbrone Jr. A new in vitro model to evaluate differential responses of endothelial cells to simulated arterial shear stress waveforms. J. Biomech. Eng. 124:397–407, 2002.CrossRefGoogle Scholar
  6. 6.
    Bolz, S. S., S. Pieperhoff, C. de Wit, and U. Pohl. Intact endothelial and smooth muscle function in small resistance arteries after 48 h in vessel culture. Am. J. Physiol. Heart Circ. Physiol. 279:H1434–H1439, 2000.Google Scholar
  7. 7.
    Bonetti, P. O., D. R. Holmes Jr., A. Lerman, and G. W. Barsness. Enhanced external counterpulsation for ischemic heart disease: What's behind the curtain? J. Am. Coll. Cardiol. 41:1918–1925, 2003.Google Scholar
  8. 8.
    Ceravolo, R., R. Maio, A. Pujia, A. Sciacqua, G. Ventura, M. C. Costa, G. Sesti, and F. Perticone. Pulse pressure and endothelial dysfunction in never-treated hypertensive patients. J. Am. Coll. Cardiol. 41:1753–1758, 2003.CrossRefGoogle Scholar
  9. 9.
    Chobanian, A. V. Vascular effects of systemic hypertension. Am. J. Cardiol. 69:3E–7E, 1992.Google Scholar
  10. 10.
    Dai, G., M. R. Kaazempur-Mofrad, S. Natarajan, Y. Zhang, S. Vaughn, B. R. Blackman, R. D. Kamm, G. Garcia-Cardena, and M. A. Gimbrone Jr. Distinct endothelial phenotypes evoked by arterial waveforms derived from atherosclerosis-susceptible and -resistant regions of human vasculature. Proc. Natl. Acad. Sci. U.S.A. 101:14871–14876, 2004.Google Scholar
  11. 11.
    Dzau, V. J., and G. H. Gibbons. Vascular remodeling: Mechanisms and implications. J. Cardiovasc. Pharmacol. 21(Suppl. 1):S1–S5, 1993.Google Scholar
  12. 12.
    Gan, L., L. S. Sjogren, R. Doroudi, and S. Jern. A new computerized biomechanical perfusion model for ex vivo study of fluid mechanical forces in intact conduit vessels. J. Vasc. Res. 36:68–78, 1999.CrossRefGoogle Scholar
  13. 13.
    Gibbons, G., and V. J. Dzau. Mechanisms of disease: The emerging concept of vascular remodleing. N. Engl. J. Med. 330:1431–1438, 1994.CrossRefGoogle Scholar
  14. 14.
    Gimbrone, M. A. Jr., J. N. Topper, T. Nagel, K. R. Anderson, and G. Garcia-Cardena. Endothelial dysfunction, hemodynamic forces, and atherogenesis. Ann. N.Y. Acad. Sci. 902:230–239; discussion 239–240, 2000.Google Scholar
  15. 15.
    Glagov, S., E. Weisenberg, C. K. Zarins, R. Stankunavicius, and G. J. Kolettis. Compensatory enlargement of human atherosclerotic coronary arteries. N. Engl. J. Med. 316:1371–1375, 1987.CrossRefGoogle Scholar
  16. 16.
    Glagov, S., C. Zarins, D. P. Giddens, and D. N. Ku. Hemodynamics and atherosclerosis. Insights and perspectives gained from studies of human arteries. Arch. Pathol. Lab. Med. 112:1018–1031, 1988.Google Scholar
  17. 17.
    Gokce, N., J. A. Vita, D. S. Bader, D. L. Sherman, L. M. Hunter, M. Holbrook, C. O'Malley, J. F. Keaney Jr., and G. J. Balady. Effect of exercise on upper and lower extremity endothelial function in patients with coronary artery disease. Am. J. Cardiol. 90:124–127, 2002.CrossRefGoogle Scholar
  18. 18.
    Hambrecht, R., V. Adams, S. Erbs, A. Linke, N. Krankel, Y. Shu, Y. Baither, S. Gielen, H. Thiele, J. F. Gummert, F. W. Mohr, and G. Schuler. Regular physical activity improves endothelial function in patients with coronary artery disease by increasing phosphorylation of endothelial nitric oxide synthase. Circulation 107:3152–3158, 2003.CrossRefGoogle Scholar
  19. 19.
    Hambrecht, R., A. Wolf, S. Gielen, A. Linke, J. Hofer, S. Erbs, N. Schoene, and G. Schuler. Effect of exercise on coronary endothelial function in patients with coronary artery disease. N. Engl. J. Med. 342:454–460, 2000.CrossRefGoogle Scholar
  20. 20.
    Hendrickson, R. J., C. Cappadona, E. N. Yankah, J. V. Sitzmann, P. A. Cahill, and E. M. Redmond. Sustained pulsatile flow regulates endothelial nitric oxide synthase and cyclooxygenase expression in cocultured vascular endothelial and smooth muscle cells. J. Mol. Cell. Cardiol. 31:619–629, 1999.CrossRefGoogle Scholar
  21. 21.
    Hutcheson, I. R., and T. M. Griffith. Release of endothelium-derived relaxing factor is modulated both by frequency and amplitude of pulsatile flow. Am. J. Physiol. 261:H257–H262, 1991.Google Scholar
  22. 22.
    Lelkes, P. I. E. Mechanical Forces and the Endothelium. Amsterdam: Harwood Academic, 1999.Google Scholar
  23. 23.
    Malek, A. M., S. L. Alper, and S. Izumo. Hemodynamic shear stress and its role in atherosclerosis. JAMA 282:2035–2042, 1999.CrossRefGoogle Scholar
  24. 24.
    Mitchell, G. F. Pulse pressure, arterial compliance, and cardiovascular morbidity and mortality. Curr. Opin. Nephrol. Hypertens. 8:335–342, 1999.CrossRefGoogle Scholar
  25. 25.
    Nackman, G. B., M. F. Fillinger, R. Shafritz, T. Wir, and A. M. Graham. Flow modulates endothelial regulation of smooth muscle cell proliferation: A new model. Surgery 124:353–360, 1998.Google Scholar
  26. 26.
    Oano Sorop, J. A. E. S., and E. Vanbavel. Pulsation-induced dilation of subendocardial and subepicardial arterioles: Effect on vasodilator sensitivity. Am. J. Physiol. Heart Circ. Physiol. 282:311–319, 2002.Google Scholar
  27. 27.
    Peng, X., S. Haldar, S. Deshpande, K. Irani, and D. A. Kass. Wall stiffness suppresses Akt/eNOS and cytoprotection in pulse-perfused endothelium. Hypertension 41:378–381, 2003.Google Scholar
  28. 28.
    Peng, X., F. A. Recchia, B. J. Byrne, I. S. Wittstein, R. C. Ziegelstein, and D. A. Kass. In vitro system to study realistic pulsatile flow and stretch signaling in cultured vascular cells. Am. J. Physiol. Cell Physiol. 279:C797–C805, 2000.Google Scholar
  29. 29.
    Qiu, Y., and J. M. Tarbell. Interaction between wall shear stress and circumferential strain affects endothelial cell biochemical production. J. Vasc. Res. 37:147–157, 2000.CrossRefGoogle Scholar
  30. 30.
    Topper, J. N., and M. A. Gimbrone Jr. Blood flow and vascular gene expression: Fluid shear stress as a modulator of endothelial phenotype. Mol. Med. Today 5:40–46, 1999.Google Scholar
  31. 31.
    vanBavel, E., T. Mooij, M. J. Giezeman, and J. A. Spaan. Cannulation and continuous cross-sectional area measurement of small blood vessels. J. Pharmacol. Methods 24:219–227, 1990.CrossRefGoogle Scholar
  32. 32.
    Zhao, S., A. Suciu, T. Ziegler, J. E. Moore Jr., E. Burki, J. J. Meister, and H. R. Brunner. Synergistic effects of fluid shear stress and cyclic circumferential stretch on vascular endothelial cell morphology and cytoskeleton. Arterioscler. Thromb. Vasc. Biol. 15:1781–1786, 1995.Google Scholar
  33. 33.
    Ziegler, T., R. W. Alexander, and R. M. Nerem. An endothelialcell-smooth muscle cell coculture model for use in the investigation of flow effects on vascular biology. Ann. Biomed. Eng. 23:216–225, 1995.Google Scholar
  34. 34.
    Ziegler, T., K. Bouzourene, V. J. Harrison, H. R. Brunner, and D. Hayoz. Influence of oscillatory and unidirectional flow environments on the expression of endothelin and nitric oxide synthase in cultured endothelial cells. Arterioscler. Thromb. Vasc. Biol. 18:686–692, 1998.Google Scholar

Copyright information

© Biomedical Engineering Society 2005

Authors and Affiliations

  • Niklas Bergh
    • 1
  • Mikael Ekman
  • Erik Ulfhammer
    • 1
  • Maria Andersson
    • 1
  • Lena Karlsson
    • 1
  • Sverker Jern
    • 1
    • 2
  1. 1.Clinical Experimental Research Laboratory, Heart and Lung Institute, Sahlgrenska University Hospital/ÖstraGöteborg UniversityGöteborgSweden
  2. 2.Clinical Experimental Research LaboratorySahlgrenska University Hospital/ÖstraGöteborgSweden

Personalised recommendations