Skip to main content
Log in

Effect of bivalirudin on neointimal hyperplasia and endothelial proliferation in rabbit

  • Original Article
  • Published:
General Thoracic and Cardiovascular Surgery Aims and scope Submit manuscript

Abstract

Background

The aim of this study was to investigate the effects of bivalirudin on endothelial cell proliferation and neointimal hyperplasia in a rabbit carotid artery model.

Methods

“New Zealand rabbits (n = 12)” weighing 2–3 kg were randomly divided into two groups. Arteriotomy was performed to the rabbit carotid artery and closed with continuous suture technique. Group B (n = 6) as a control group received 150 U/kg heparin sodium; however, group A (n = 6) was given 0.75 mg/kg bivalirudin i.v. bolus and infusion 1.75 mg/kg/hour (B01AE06-Bivalirudin 250 mg) during perioperation period. At the end of the 28th day, the carotid artery segment was excised and evaluated histologically.

Results

All histological and immune staining analyzes were performed by two blind researchers in the treatment of rabbits. In the control group rabbit carotid artery sections, tunica intima was observed to thicken. In the bivalirudin group, intimal hyperplasia was less observed compared to the control group. No significant difference was observed between groups in tunica media thickness. Lumen diameter and lumen area were found to be wider in the experimental group. P value was found to be less than 0.05.

Conclusion

Our study demonstrates that bivalirudin significantly affects and prevents neointimal hyperplasia and endothelial cell proliferation.

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

Access this article

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

Instant access to the full article PDF.

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

Similar content being viewed by others

References

  1. Chen X, Ren S, Ma MG, Sudharshan D, Lin L, Mengzhou X, et al. Hirulog-like peptide reduces restenosis and expression of tissue factor and transforming growth factor-beta in carotid artery of atherosclerotic rabbits. Atherosclerosis. 2003;169(1):31–40.

    Article  CAS  Google Scholar 

  2. Akkaya G, Bilen C, Gencpinar T, Akokay P, Uğurlu B. Effects of rivaroxaban on intimal hyperplasia and smooth muscle cell proliferation at the carotid artery anastomosis site in rabbits. Anatol J Cardiol. 2017;18(4):261–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Anand S, Kim M, Kamran C, Samin KS, Annapoorna SK, Fareed J, et al. Comparison of platelet function and morphology in patients undergoing percutaneous coronary ıntervention receiving bivalirudin versus unfractionated heparin versus clopidogrel pretreatment and bivalirudin. Am J Cardiol. 2007;100(3):417–24.

    Article  CAS  Google Scholar 

  4. Stone GW, McLaurin BT, Cox DA, Bertrand ME, Lincoff AM, Moses JW, et al. Bivalirudin for patients with acute coronary syndromes. N Engl J Med. 2006;355(21):2203–16.

    Article  CAS  Google Scholar 

  5. Weitz J, Bates M. Acute coronary syndromes: A focus on thrombin. J Invasive Cardiol. 2002;14(Suppl B):2B–7B.

    PubMed  Google Scholar 

  6. Hasija S, Talwar S, Makhija N, Sandeep C, Poonam M, Ujjwal KC, et al. Randomized controlled trial of heparin versus bivalirudin anticoagulation in acyanotic children undergoing open heart surgery. J Cardiothorac Vasc Anesth. 2018;32(6):2633–40.

    Article  CAS  Google Scholar 

  7. Shore-Lesserson L, Baker RA, Ferraris V, Greilich PE, Fitzgerald D, Roman P, et al. STS/SCA/AmSECT clinical practice guidelines: anticoagulation during cardiopulmonary bypass. J Extra Corpor Technol. 2018;50(1):5–18.

    PubMed  PubMed Central  Google Scholar 

  8. Yau JW, Stafford AR, Liao P, Robin R, Weitz J. Mechanism of catheter thrombosis: comparison of the antithrombotic activities of fondaparinux, enoxaparin, and heparin in vitro and in vivo. Blood. 2011;118(25):6667–74.

    Article  CAS  Google Scholar 

  9. Füreder L, Böhmig GA, Schaefer AK, Steinlechner B. Extracorporeal immunoadsorption in heparin- and protamine-induced thrombocytopaenia prior to cardiac surgery. Eur J Cardiothorac Surg. 2019;56(1):206–7.

    Article  Google Scholar 

  10. Warkentin TE. Heparin-induced thrombocytopenia in critically ill patients. Semin Thromb Hemost. 2015;41:49–60.

    Article  CAS  Google Scholar 

  11. Dunning J, Versteegh M, Fabbri A, Pavie A, Kolh P, Lockowandt U, et al. Guideline on antiplatelet and anticoagulation management in cardiac surgery. Eur J Cardiothorac Surg. 2008;34:73–92.

    Article  Google Scholar 

  12. Wang JH, Cao FL, Huang YL. Inhibitory effect of irbesartan on restenosis after balloon angioplasty and mechanism thereof: experiment with rabbits. Zhonghua Yi Xue Za Zhi. 2006;86(34):2395–8.

    CAS  PubMed  Google Scholar 

  13. Lauth M, Cattaruzza M, Hecker M. ACE inhibitor and AT1 antagonist blockade of deformation-induced gene expression in the rabbit jugular vein through B2 receptor activation. Arterioscler Thromb Vasc Biol. 2001;21(1):61–6.

    Article  CAS  Google Scholar 

  14. Ghigliotti G, Mereto E, Eisenberg PR, Martelli A, Orsi P, Sini D, et al. N-acetyl-cysteine reduces neointimal thickening and procoagulant activity after balloon-induced injury in abdominal aortae of New Zealand white rabbits. Thromb Haemost. 2001;85(4):724–9.

    Article  CAS  Google Scholar 

  15. Chang CC, Chichareon P, Modolo R, Takahashi K, Kogame N, Tomaniak M, et al. Association between post-percutaneous coronary intervention bivalirudin infusion and net adverse clinical events: a post hoc analysis of the GLOBAL LEADERS study. Eur Heart J Cardiovasc Pharmacother. 2019. https://doi.org/10.1093/ehjcvp/pvz051.

    Article  Google Scholar 

Download references

Funding

The authors received no financial support for the research or authorship of this article.

Author information

Authors and Affiliations

Authors

Contributions

Concept—PA and TG; design—TG and BK; supervision—SB, BK, PA, and MB; resource—CB; materials—TG; data collection and/or processing—TG and CE; analysis—CE and CB; literature search—TG, MB, and CB; writing—TG and BK; critical review—CB; other—PA. All authors approved the final version of the manuscript.

Corresponding author

Correspondence to Tugra Gencpinar.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gencpinar, T., Bayrak, S., Bilen, C. et al. Effect of bivalirudin on neointimal hyperplasia and endothelial proliferation in rabbit. Gen Thorac Cardiovasc Surg 69, 425–433 (2021). https://doi.org/10.1007/s11748-020-01454-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11748-020-01454-8

Keywords

Navigation