Skip to main content
SpringerLink
Log in

Method for Percutaneously Introducing, and Removing, Anatomical Stenosis of Predetermined Severity In Vivo: The “Stenotic Stent”

  • Published:
Journal of Cardiovascular Translational Research Aims and scope Submit manuscript

Abstract

Current in vivo models of arterial lesions often lead to unpredictable results in terms of lesion anatomy and hemodynamical significance. This study aimed to evaluate the impact of coronary stenosis using a novel in vivo adjustable stenosis model capable of mimicking advanced human coronary lesions. We developed a series of balloon expandable covered coronary stents with a central restriction, mimicking different intermediate to severe stenosis, and implanted them percutaneously in coronary arteries of eight healthy hybrid Landrace pigs. Optical coherence tomography (OCT) pullbacks and fractional flow reserve (FFR) were acquired along the artery after implantation of the stenotic stents for precise evaluation of anatomy and functional impact. Diameter and area stenosis after deployment of the stenosis implant were, on average, respectively, 54.1 ± 5.9 and 78.4 ± 5.8 % and average FFR value was 0.83 (SD 0.13). There was a low correlation between FFR and MLA evaluated by OCT (r = 0.02, p = 0.94), improved with percentage area stenosis (r = −0.55, p = 0.12), or OCT volumetric evaluation of the stenosis taking into account not only the MLA but also the length of the lesion (r = −0.78, p = 0.01). This study presents a method and proof of concept for percutaneously introducing, and removing, anatomical stenosis of predetermined severity in vivo. Such in vivo model may be used to create and evaluate the impact of focal stenoses on physiological parameters such as FFR.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

CAD:

Coronary artery diseases

CFD:

Computational flow dynamic

CT:

Computed tomography

IVUS:

Intravascular ultrasound

FFR:

Fractional flow reserve

MLD:

Minimum lumen diameter

MLA:

Minimum lumen area

MLV:

Minimum lumen volume

OCT:

Optical coherence tomography

QCA:

Quantitative coronary angiography

References

  1. Suzuki, Y., Yeung, A. C., & Ikeno, F. (2009). The pre-clinical animal model in the translational research of interventional cardiology. JACC Cardiovascular Interventions, 2, 373–383.

    Article  PubMed  Google Scholar 

  2. FDA. General considerations for animal studies for cardiovascular devices. Guidance for Industry and FDA Staff 2010;Center for Devices and Radiological Health.

  3. Pijls, N., van Son, J., Kirkeeide, R., De Bruyne, B., & Gould, K. (1993). Experimental basis of determining maximum coronary, myocardial, and collateral blood flow by pressure measurements for assessing functional stenosis severity before and after percutaneous transluminal coronary angioplasty. Circulation, 87, 1354–1367.

    Article  PubMed  CAS  Google Scholar 

  4. Folts, J., Crowell, E., Jr., & Rowe, G. (1976). Platelet aggregation in partially obstructed vessels and its elimination with aspirin. Circulation, 54, 365–370.

    Article  PubMed  CAS  Google Scholar 

  5. Schaper, W., Schaper, J., Xhonneux, R., & Vandesteene, R. (1969). The morphology of intercoronary anastomoses in chronic coronary artery occlusion. Cardiovascular Research, 3, 315–323.

    Article  PubMed  CAS  Google Scholar 

  6. Roth, D. M., Maruoka, Y., Rogers, J., White, F. C., Longhurst, J. C., & Bloor, C. M. (1987). Development of coronary collateral circulation in left circumflex ameroid-occluded swine myocardium. American Journal of Physiology. Heart and Circulatory Physiology, 253, H1279–H1288.

    CAS  Google Scholar 

  7. Hughes, G. C., Post, M. J., Simons, M., & Annex, B. H. (2003). Translational physiology: porcine models of human coronary artery disease: implications for preclinical trials of therapeutic angiogenesis. Journal of Applied Physiology, 94, 1689–1701.

    PubMed  Google Scholar 

  8. Litvak, J., Siderides, L. E., & Vineberg, A. M. (1957). The experimental production of coronary artery insufficiency and occlusion. American Heart Journal, 53, 505–518.

    Article  PubMed  CAS  Google Scholar 

  9. von Georges, D., Philip, R., Christian, K., Corinna, L., Rabea, H., Franz Josef, G., Wolfgang, M. N., Andrea, K., Johannes, W., Marcus, S., Markus, S., Eckart, T., & Peter, B. (2003). Selective pressure-regulated retroinfusion of fibroblast growth factor-2 into the coronary vein enhances regional myocardial blood flow and function in pigs with chronic myocardial ischemia. Journal of the American College of Cardiology, 42, 1120–1128.

    Article  Google Scholar 

  10. Lazoura O, Zacharoulis D, Kanavou T, Rountas C, Katsimboulas M, Tzovaras G, Habib N. A novel experimental animal model of arterial stenosis based on endovascular radiofrequency energy application. Journal of Investigative Surgery.24:123-128

  11. Suzuki, Y. (2008). The porcine restenosis model using thermal balloon injury: comparison with the model by coronary stenting. The Journal of Invasive Cardiology, 20, 142.

    PubMed  Google Scholar 

  12. Wu, M., Bogaert, J., D'hooge, J., Sipido, K., Maes, F., Dymarkowski, S., Rademakers, F., & Claus, P. (2010). Closed-chest animal model of chronic coronary artery stenosis. Assessment with magnetic resonance imaging. The International Journal of Cardiovascular Imaging, 26, 299–308. formerly Cardiac Imaging.

    Article  PubMed  Google Scholar 

  13. Staab, M. E., Meeker, D. K., Edwards, W. D., Camrud, A. R., Jorgenson, M. A., Camrud, L. J., Srivatsa, S. S., Jeong, M. H., Gregoire, J., Holmes, D. R., & Schwartz, R. S. (1997). Reliable models of severe coronary stenosis in porcine coronary arteries: lesion induction by high temperature or copper stent. Journal of Interventional Cardiology, 10, 61–69.

    Article  Google Scholar 

  14. Mintz, G. S., Nissen, S. E., Anderson, W. D., Bailey, S. R., Erbel, R., Fitzgerald, P. J., Pinto, F. J., Rosenfield, K., Siegel, R. J., Tuzcu, E. M., Yock, P. G., O’Rourke, R. A., Abrams, J., Bates, E. R., Brodie, B. R., Douglas, P. S., Gregoratos, G., Hlatky, M. A., Hochman, J. S., Kaul, S., Tracy, C. M., Waters, D. D., & Winters, W. L., Jr. (2001). American College of Cardiology clinical expert consensus document on standards for acquisition, measurement and reporting of intravascular ultrasound studies (IVUS): a report of the american college of cardiology task force on clinical expert consensus documents developed in collaboration with the european society of cardiology endorsed by the society of cardiac angiography and interventions. Journal of the American College of Cardiology, 37, 1478–1492.

    Article  PubMed  CAS  Google Scholar 

  15. Yong ASC, Ng ACC, Brieger D, Lowe HC, Ng MKC, Kritharides L. Three-dimensional and two-dimensional quantitative coronary angiography, and their prediction of reduced fractional flow reserve. European Heart Journal. 2010.

  16. Kolozsvári R, Tar B, Lugosi P, Sánta J, Béres Z, Ungvári T, Polgár P, Kőszegi Z. Plaque volume derived from three-dimensional reconstruction of coronary angiography predicts the fractional flow reserve. International Journal of Cardiology. 2011;in press.

  17. Francis DP. How easily can omission of patients, or selection amongst poorly-reproducible measurements, create artificial correlations? Methods for detection and implications for observational research design in cardiology. International Journal of Cardiology.

  18. Sinha Roy, A., Back, M. R., Khoury, S. F., Schneeberger, E. W., Back, L. H., Velury, V. V., Millard, R. W., & Banerjee, R. K. (2008). Functional and anatomical diagnosis of coronary artery stenoses. The Journal of Surgical Research, 150, 24–33.

    Article  PubMed  Google Scholar 

  19. Kroma, G., Lopera, J., Cura, M., Suri, R., El-Merhi, F., & Reading, J. (2009). Transjugular intrahepatic portosystemic shunt flow reduction with adjustable polytetrafluoroethylene-covered balloon-expandable stents. Journal of Vascular and Interventional Radiology JVIR, 20, 981–986.

    Article  PubMed  Google Scholar 

  20. Young, D., Cholvin, N., & Roth, A. (1975). Pressure drop across artificially induced stenoses in the femoral arteries of dogs. Circulation Research, 36, 735–743.

    Article  PubMed  CAS  Google Scholar 

  21. McMahon, M., Brown, B., Cukingnan, R., Rolett, E., Bolson, E., Frimer, M., & Dodge, H. (1979). Quantitative coronary angiography: measurement of the “critical” stenosis in patients with unstable angina and single-vessel disease without collaterals. Circulation, 60, 106–113.

    Article  PubMed  CAS  Google Scholar 

  22. Eklöf, B. (1970). Critical stenosis of the carotid artery in the dog. Scandinavian Journal of Clinical and Laboratory Investigation, 25, 349.

    Article  PubMed  Google Scholar 

  23. Gould, K., Kirkeeide, R., & Buchi, M. (1990). Coronary flow reserve as a physiologic measure of stenosis severity. Journal of the American College of Cardiology, 15, 459–474.

    Article  PubMed  CAS  Google Scholar 

  24. Waksman, R., Legutko, J., Singh, J., Orlando, Q., Marso, S., Schloss, T., Tugaoen, J., DeVries, J., Palmer, N., Haude, M., Swymelar, S., & Torguson, R. (2013). First: fractional flow reserve and intravascular ultrasound relationship study. Journal of the American College of Cardiology, 61, 917–923.

    Article  PubMed  Google Scholar 

  25. Kang, S.-J., Lee, J.-Y., Ahn, J.-M., Mintz, G. S., Kim, W.-J., Park, D.-W., Yun, S.-C., Lee, S.-W., Kim, Y.-H., Whan Lee, C., Park, S.-W., & Park, S.-J. (2011). Validation of intravascular ultrasound-derived parameters with fractional flow reserve for assessment of coronary stenosis severity/clinical perspective. Circulation. Cardiovascular Interventions, 4, 65–71.

    Article  PubMed  Google Scholar 

  26. Koo, B.-K., Yang, H.-M., Doh, J.-H., Choe, H., Lee, S.-Y., Yoon, C.-H., Cho, Y.-K., Nam, C.-W., Hur, S.-H., Lim, H.-S., Yoon, M.-H., Park, K.-W., Na, S.-H., Youn, T.-J., Chung, W.-Y., Ma, S., Park, S.-K., Kim, H.-S., & Tahk, S.-J. (2011). Optimal intravascular ultrasound criteria and their accuracy for defining the functional significance of intermediate coronary stenoses of different locations. Journal of the American College of Cardiology: Cardiovascular Interventions, 4, 803–811.

    Google Scholar 

  27. Ben-Dor, I., Torguson, R., Gaglia, M. A., Jr., Gonzalez, M. A., Maluenda, G., Bui, A. B., Xue, Z., Satler, L. F., Suddath, W. O., Lindsay, J., Pichard, A. D., & Waksman, R. (2011). Correlation between fractional flow reserve and intravascular ultrasound lumen area in intermediate coronary artery stenosis. EuroIntervention, 7, 225–233.

    Article  PubMed  Google Scholar 

  28. Goldstein, R. A., Kirkeeide, R. L., Demer, L. L., Merhige, M., Nishikawa, A., Smalling, R. W., Mullani, N. A., & Gould, K. L. (1987). Relation between geometric dimensions of coronary artery stenoses and myocardial perfusion reserve in man. The Journal of Clinical Investigation, 79, 1473–1478.

    Article  PubMed  CAS  Google Scholar 

  29. Brosh, D., Higano, S. T., Lennon, R. J., Holmes, D. R., Jr., & Lerman, A. (2005). Effect of lesion length on fractional flow reserve in intermediate coronary lesions. American Heart Journal, 150, 338–343.

    Article  PubMed  Google Scholar 

  30. Kristensen, T. S., Engstrøm, T., Kelbæk, H., von der Recke, P., Nielsen, M. B., & Kofoed, K. F. (2010). Correlation between coronary computed tomographic angiography and fractional flow reserve. International Journal of Cardiology, 144, 200–205.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to acknowledge the support of Amelie Bouchard, Martin Laflamme, Louis George Guy, and the Accellab team for their support in conducting the animal experiments.

Sources of funding

The authors acknowledge support from the Wellcome Trust Foundation for this study. Dr. Nijjer (G1100443) and Dr. Sen (G1000357) are Medical Research Council fellows. Dr. Petraco (FS/11/46/28861), Dr. JE Davies (FS/05/006), and Dr. Francis (FS 10/038) are British Heart Foundation fellows.

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. International Centre for Circulatory Health, NHLI, Imperial College London, London, UK

    Nicolas Foin, Sayan Sen, Ricardo Petraco, Sukhjinder Nijjer, Chrysa Kousera, Christopher Broyd, Jamil Mayet, Alun Hughes, Darrel Francis & Justin Davies

  2. Department of Bioengineering, Imperial College London, London, UK

    Vikram Mehta & Rob Krams

  3. Chemical Engineering, Imperial College London, London, UK

    Ryo Torii & Yun Xu

  4. Biomedical Research Unit, Royal Brompton and Harefield NHS Trust, London, UK

    Carlo Di Mario

Authors
  1. Nicolas Foin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sayan Sen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ricardo Petraco
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sukhjinder Nijjer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ryo Torii
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Chrysa Kousera
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Christopher Broyd
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Vikram Mehta
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yun Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jamil Mayet
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Alun Hughes
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Carlo Di Mario
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Rob Krams
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Darrel Francis
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Justin Davies
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nicolas Foin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Foin, N., Sen, S., Petraco, R. et al. Method for Percutaneously Introducing, and Removing, Anatomical Stenosis of Predetermined Severity In Vivo: The “Stenotic Stent”. J. of Cardiovasc. Trans. Res. 6, 640–648 (2013). https://doi.org/10.1007/s12265-013-9476-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12265-013-9476-x

Keywords

Search

Navigation