Skip to main content
SpringerLink
Log in

ATP Transport in Saccular Cerebral Aneurysms at Arterial Bends

  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

ATP acts as an extracellular signaling molecule in purinergic signaling that regulates vascular tone. ATP binds purinergic P2 nucleotide receptors on endothelial cells. Understanding the mass transport of ATP to endothelial cells by blood flow is thus important to predict functional changes in aneurysmal walls. While some clinical observations indicate a difference of wall pathology between ruptured and unruptured aneurysms, no study has focused on the mass transport in aneurysms. We investigated the characteristics of ATP concentration at aneurysmal wall using a numerical model of ATP transport in aneurysms formed at arterial bends. The magnitude of ATP concentration at the aneurysmal wall was significantly smaller than that at the arterial wall. In particular, significantly low concentration was predicted at the proximal side of the aneurysmal sac. A strong correlation was revealed between the inflow flux at the aneurysmal neck and the resultant concentration at the aneurysmal wall.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

FIGURE 1
FIGURE 2
FIGURE 3
FIGURE 4
FIGURE 5
FIGURE 6

Similar content being viewed by others

References

  1. Bodin, P., and G. Burnstock. ATP-stimulated release of ATP by human endothelial cells. J. Cardiovasc. Pharmacol. 27:872–875, 1996.

    Article  PubMed  CAS  Google Scholar 

  2. Boussel, L., V. Rayz, C. McCulloch, A. Martin, G. Acevedo-Bolton, M. Lawton, R. Higashida, W. S. Smith, W. L. Young, and D. Saloner. Aneurysm growth occurs at region of low wall shear stress: patient-specific correlation of hemodynamics and growth in a longitudinal study. Stroke 39:2997–3002, 2008.

    Article  PubMed  Google Scholar 

  3. Burnstock, G. Purinergic signaling and vascular cell proliferation and death. Arterioscler. Thromb. Vasc. Biol. 22:364–373, 2002.

    Article  PubMed  CAS  Google Scholar 

  4. Burnstock, G. Introduction: P2 receptors. Curr. Top. Med. Chem. 4:793–803, 2004.

    Article  PubMed  CAS  Google Scholar 

  5. Burnstock, G. Vessel tone and remodeling. Nat. Med. 12:16–17, 2006.

    Article  PubMed  CAS  Google Scholar 

  6. Caro, C. G., J. M. Fitz-Gerald, and R. C. Schroter. Atheroma and arterial wall shear. Observation, correlation and proposal of a shear dependent mass, transfer mechanism for atherogenesis. Proc. R. Soc. Lond. Ser. B 177:109–159, 1971.

    Article  CAS  Google Scholar 

  7. Choi, H. W., K. W. Ferrara, and A. I. Barakat. Modulation of ATP/ADP concentration at the endothelial surface by shear stress: effect of flow recirculation. Ann. Biomed. Eng. 35:505–516, 2007.

    Article  PubMed  Google Scholar 

  8. Comerford, A., and T. David. Computer model of nucleotide transport in a realistic porcine aortic trifurcation. Ann. Biomed. Eng. 36:1175–1187, 2008.

    Article  PubMed  Google Scholar 

  9. Comerford, A., T. David, and M. Plank. Effects of arterial bifurcation geometry on nucleotide concentration at the endothelium. Ann. Biomed. Eng. 34:605–617, 2006.

    Article  PubMed  Google Scholar 

  10. Comerford, A., M. J. Plank, and T. David. Endothelial nitric oxide synthase and calcium production in arterial geometries: an integrated fluid mechanics/cell model. J. Biomech. Eng. 130:011010, 2008.

    Article  PubMed  CAS  Google Scholar 

  11. Crawford, D. W., and D. H. Blankenhorn. Arterial wall oxygenation, oxyradicals, and atherosclerosis. Atherosclerosis 89:97–108, 1991.

    Article  PubMed  CAS  Google Scholar 

  12. da Silva, C. G., A. Specht, B. Wegiel, C. Ferran, and E. Kaczmarek. Mechanism of purinergic activation of endothelial nitric oxide synthase in endothelial cells. Circulation 119:871–879, 2009.

    Article  PubMed  CAS  Google Scholar 

  13. David, T. Wall shear stress modulation of ATP/ADP concentration at the endothelium. Ann. Biomed. Eng. 31:1231–1237, 2003.

    Article  PubMed  Google Scholar 

  14. Erlinge, D., and G. Burnstock. P2 receptors in cardiovascular regulation and disease. Purinergic Signal. 4:1–20, 2008.

    Article  PubMed  CAS  Google Scholar 

  15. Ethier, C. R. Computational modeling of mass transfer and links to atherosclerosis. Ann. Biomed. Eng. 30:461–471, 2002.

    Article  PubMed  Google Scholar 

  16. Ford, M. D., S.-W. Lee, S. P. Lownie, D. W. Holdsworth, and D. A. Steinman. On the effect of parent-aneurysm angle on flow patterns in basilar tip aneurysms: toward a surrogate geometric marker of intra-aneurysmal hemodynamics. J. Biomech. 41:241–248, 2008.

    Article  PubMed  Google Scholar 

  17. Frösen, J., A. Piippo, A. Paetau, M. Kangasniemi, M. Niemelä, J. Hernesniemi, and J. Jääskeläinen. Remodeling of saccular cerebral artery aneurysm wall is associated with rupture: histological analysis of 24 unruptured and 42 ruptured cases. Stroke 35:2287–2293, 2004.

    Article  PubMed  Google Scholar 

  18. Hoff, H. F., C. L. Heideman, R. L. Jackson, R. J. Bayardo, H. S. Kim, and A. M. J. Gotto. Localization patterns of plasma apolipoproteins in human atherosclerotic lesions. Circ. Res. 37:72–79, 1975.

    PubMed  CAS  Google Scholar 

  19. Imai, Y., K. Sato, T. Ishikawa, and T. Yamaguchi. Inflow into saccular cerebral aneurysms at arterial bends. Ann. Biomed. Eng. 36:1489–1495, 2008.

    Article  PubMed  Google Scholar 

  20. International Study of Unruptured Intracranial Aneurysms Investigators. Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet 362:103–110, 2003.

    Article  Google Scholar 

  21. John, K., and A. I. Barakat. Modulation of ATP/ADP concentration at the endothelial surface by shear stress: effect of flow-induced ATP release. Ann. Biomed. Eng. 29:740–751, 2001.

    Article  PubMed  CAS  Google Scholar 

  22. Kaazempur-Mofrad, M. R., and C. R. Ethier. Mass transport in an anatomically realistic human right coronary artery. Ann. Biomed. Eng. 29:121–127, 2001.

    Article  PubMed  CAS  Google Scholar 

  23. Kataoka, K., M. Taneda, T. Asai, A. Kinoshita, M. Ito, and R. Kuroda. Structural fragility and inflammatory response of ruptured cerebral aneurysms: a comparative study between ruptured and unruptured cerebral aneurysms. Stroke 30:1396–1401, 1999.

    PubMed  CAS  Google Scholar 

  24. Koshiba, N., J. Ando, X. Chen, and T. Hisada. Multiphysics simulation of blood flow and LDL transport in a porohyperelastic arterial wall model. J. Biomech. Eng. 129:374–385, 2007.

    Article  PubMed  Google Scholar 

  25. Kosierkiewicz, T. A., S. M. Factor, and D. W. Dickson. Immunocytochemical studies of atherosclerotic lesions of cerebral berry aneurysms. J. Neuropathol. Exp. Neurol. 53:399–406, 1994.

    Article  PubMed  CAS  Google Scholar 

  26. Loscalzo, J., and G. Welch. Nitric oxide and its role in the cardiovascular system. Prog. Cardiovasc. Dis. 38:87–104, 1995.

    Article  PubMed  CAS  Google Scholar 

  27. Ma, P., X. Lu, and D. N. Ku. Heat and mass transfer in a separated flow region for high Prandtl and Schmidt numbers under pulsatile flow conditions. Int. J. Heat Mass Transf. 37:2723–2736, 1994.

    Article  CAS  Google Scholar 

  28. Mantha, A., C. Karmonik, G. Benndorf, C. Strother, and R. Metcalfe. Hemodynamics in a cerebral artery before and after the formation of an aneurysm. Am. J. Neuroradiol. 27:1113–1118, 2006.

    PubMed  CAS  Google Scholar 

  29. Moore, J. A., and C. R. Ethier. Oxygen mass transfer calculations in large arteries. J. Biomech. Eng. 19:469–475, 1997.

    Article  Google Scholar 

  30. Ohno, K., T. Arai, E. Isotani, T. Nariai, and K. Hirakawa. Ischaemic complication following obliteration of unruptured cerebral aneurysms with atherosclerotic or calcified neck. Acta Neurochir. (Wien) 141:699–706, 1999.

    Article  CAS  Google Scholar 

  31. Patankar, S. V., and D. B. Spalding. A calculation procedure for heat, mass and momentum transfer in three-dimensional parabolic flows. Int. J. Heat Mass Transf. 15:1787–1803, 1972.

    Article  Google Scholar 

  32. Perlea, L., R. Fahrig, D. W. Holdsworth, and S. P. Lownie. An analysis of the geometry of saccular intracranial aneurysms. Am. J. Neuroradiol. 20:1079–1089, 1999.

    Google Scholar 

  33. Ralevic, V., and G. Burnstock. Receptors for purines and pyrimidines. Pharmacol. Rev. 50:423–492, 1998.

    Google Scholar 

  34. Rappitsch, G., and K. Perktold. Computer simulation of convective diffusion processes in large arteries. J. Biomech. 29:207–215, 1996.

    Article  PubMed  CAS  Google Scholar 

  35. Ross, R. Atherosclerosis: a defense mechanism gone awry. Am. J. Pathol. 143:987–1002, 1993.

    PubMed  CAS  Google Scholar 

  36. Sato, K., Y. Imai, T. Ishikawa, N. Matsuki, and T. Yamaguchi. The importance of parent artery geometry in intra-aneurysmal hemodynamics. Med. Eng. Phys. 30:774–782, 2008.

    Article  PubMed  Google Scholar 

  37. Shen, J., M. A. Gimbrone, F. W. Luscinskas, and C. F. Dewey. Regulation of adenine-nucleotide concentration at endothelium fluid interface by viscous shear-flow. Biophys. J. 64:1323–1330, 1993.

    Article  PubMed  CAS  Google Scholar 

  38. Shimogonya, Y., T. Ishikawa, Y. Imai, N. Matsuki, and T. Yamaguchi. Can temporal fluctuation in spatial wall shear stress gradient initiate a cerebral aneurysm? A proposed novel hemodynamic index, the gradient oscillatory number (GON). J. Biomech. 42:550–554, 2009.

    Article  PubMed  Google Scholar 

  39. Shimogonya, Y., T. Ishikawa, Y. Imai, N. Matsuki, and T. Yamaguchi. A realistic simulation of saccular cerebral aneurysm formation: focusing on a novel hemodynamic index, the gradient oscillatory number (GON). Int. J. Comput. Fluid Dyn. 23:583–593, 2009.

    Article  Google Scholar 

  40. Shojima, M., M. Oshima, K. Takagi, R. Torii, M. Hayakawa, K. Katada, A. Morita, and T. Kirino. Magnitude and role of wall shear stress on cerebral aneurysm: computational fluid dynamics study of 20 middle cerebral artery aneurysms. Stroke 35:2500–2505, 2004.

    Article  PubMed  Google Scholar 

  41. Sudo, K., M. Sumida, and R. Yamane. Secondary motion of fully developed oscillatory flow in a curved pipe. J. Fluid Mech. 237:189–208, 1992.

    Article  CAS  Google Scholar 

  42. Sun, N., N. B. Wood, A. D. Hughes, S. A. M. Thom, and X. Y. Xu. Influence of pulsatile flow on LDL transport in the arterial wall. Ann. Biomed. Eng. 35:1782–1790, 2007.

    Article  PubMed  Google Scholar 

  43. Tada, S., and J. M. Tarbell. Oxygen mass transport in a compliant carotid bifurcation model. Ann. Biomed. Eng. 34:1389–1399, 2006.

    Article  PubMed  Google Scholar 

  44. Tateshima, S., K. Tanishita, H. Omura, J. Sayre, J. P. Villablanca, N. Martin, and F. Vinuela. Intra-aneurysmal hemodynamics in a large middle cerebral artery aneurysm with wall atherosclerosis. Surg. Neurol. 70:454–462, 2008.

    Article  PubMed  Google Scholar 

  45. Tateshima, S., K. Tanishita, and F. Vinuela. Hemodynamics and cerebrovascular disease. Surg. Neurol. 70:447–453, 2008.

    Article  PubMed  Google Scholar 

  46. Torii, R., M. Oshima, T. Kobayashi, K. Takagi, and T. E. Tezduyar. Influence of wall elasticity in patient-specific hemodynamic simulations. Comput. Fluids 36:160–168, 2007.

    Article  Google Scholar 

  47. Ujiie, H., H. Tachibana, O. Hiramatsu, A. L. Hazel, T. Matsumoto, Y. Ogasawara, H. Nakajima, T. Hori, K. Takakura, and F. Kajiya. Effects of size and shape (aspect ratio) on the hemodynamics of saccular aneurysms: a possible index for surgical treatment of intracranial aneurysms. Neurosurgery 45:129–130, 1999.

    Article  Google Scholar 

  48. Ujiie, H., Y. Tamano, K. Sasaki, and T. Hori. Is the aspect ratio a reliable index for predicting the rupture of a saccular aneurysm? Neurosurgery 48:495–503, 2001.

    Article  PubMed  CAS  Google Scholar 

  49. Wada, S., and T. Karino. Theoretical prediction of low-density lipoproteins concentration at the luminal surface of an artery with a multiple bend. Ann. Biomed. Eng. 30:778–791, 2002.

    Article  PubMed  Google Scholar 

  50. Weir, B. Unruptured intracranial aneurysms: a review. J. Neurosurg. 96:3–42, 2002.

    Article  PubMed  Google Scholar 

  51. Yamamoto, K., T. Sokabe, T. Matsumoto, K. Yoshimura, M. Shibata, N. Ohura, T. Fukuda, T. Sato, K. Sekine, S. Kato, M. Isshiki, T. Fujita, M. Kobayashi, K. Kawamura, H. Masuda, A. Kamiya, and J. Ando. Impaired flow-dependent control of vascular tone and remodeling in P2X4-deficient mice. Nat. Med. 12:133–137, 2006.

    Article  PubMed  CAS  Google Scholar 

  52. Yoshimoto, Y., T. Ochiai, and M. Nagai. Cerebral aneurysms unrelated to arterial bifurcations. Acta Neurochir. 138:958–964, 1996.

    Article  CAS  Google Scholar 

Download references

Acknowledgment

This research was supported by Grants in Aid for Scientific Research(s) from JSPS No. 19100008 “Computational Nanobiomechanics for the diagnosis, treatment, and prevention of diseases of blood, circulatory, and digestive organs,” by 2007 Global COE Program “Global Nano-Biomedical Engineering Education and Research Network Centre,” and by Research and Development of the Next-Generation Integrated Simulation of Living Matter, a part of the Development and Use of the Next-Generation Supercomputer Project of the Ministry of Education, Culture, Sports, Science and Technology (MEXT).

Author information

Authors and Affiliations

  1. Department of Bioengineering and Robotics, Tohoku University, 6-6-01 Aramaki Aza Aoba, Aoba-ku, Sendai-shi, Miyagi, 980-8579, Japan

    Yohsuke Imai, Kodai Sato & Takuji Ishikawa

  2. Technische Universität München, Munich, Germany

    Andrew Comerford

  3. Centre for Bioengineering, University of Canterbury, Christchurch, New Zealand

    Tim David

  4. Department of Biomedical Engineering, Tohoku University, Sendai, Japan

    Takami Yamaguchi

Authors
  1. Yohsuke Imai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kodai Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Takuji Ishikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Andrew Comerford
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tim David
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Takami Yamaguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yohsuke Imai.

Additional information

Associate Editor Gerald Saidel oversaw the review of this article.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Imai, Y., Sato, K., Ishikawa, T. et al. ATP Transport in Saccular Cerebral Aneurysms at Arterial Bends. Ann Biomed Eng 38, 927–934 (2010). https://doi.org/10.1007/s10439-009-9864-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-009-9864-1

Keywords

Search

Navigation