Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Preparation and experimental research into retrievable rapamycin- and heparin-coated vena cava filters: a pilot study

  • 253 Accesses

  • 2 Citations


The use of retrievable vena cava filters (RVCFs) was once commonplace, but filter retrieval was often very difficult. Most unsuccessful retrieval was due to intimal hyperplasia of the inferior vena cava and in-filter thrombosis. This pilot study aimed to design a drug-eluting RVCF. The hypothesis was that coated drugs could be released continuously to inhibit vena intimal hyperplasia and thrombosis, and thus improve the retrieval rates of RVCFs. Various concentrations of polycaprolactone (PCL)/chloroform solution were made from a mixture of Rapamycin and Heparin according to the quality of PCL. The drug was coated onto the surface of the filters by a process of dipping. In vitro tests were performed to check stability and in vitro drug release. Animals receiving filter implantation were divided into 4 groups, the experimental intervention group (EI), experimental laparotomy group (EL), control intervention group (CI), and control laparotomy group (CL). Filters were retrieved by laparotomy in the EL and CL groups, and by interventional operation in the EI and CI groups at 10, 20 and 30 days after implantation. Pathological endothelia biopsies were performed with wood grain-eosin (HE) staining and immunohistochemical examination, with the proliferating cell nuclear antigen (PCNA) index, and the results were compared between the experimental and control groups. The weight of thrombus within the filters was also measured by scale and compared. The coating concentration that succeeded in completely covering the surface was 0.2 g/ml. There was better coverage by SEM at this concentration, and the coated drugs had no obvious loss after filter release. The drug release curves showed that the amount of Heparin released was more than 50 % at day 1; Rapamycin released little in the first few days, beginning in earnest at 20 to 30 days. The filters were easy to retrieve at 10 days for both groups, while neither could be retrieved at 30 days. However, at 20 days the filter in the EI group could be retrieved with some difficulty, but the filter in the CI group couldn’t be removed at all. The pathological examination and immunohistochemical PCNA examination results showed that the use of drug-eluting filters could effectively inhibit endothelial hyperplasia at 10 and 20 days, but was less effective at 30 days. There was no apparent difference in the total weight of blood clots between the experimental and control groups. We successfully conducted a pilot study into preparing Rapamycin- and Heparin-coated RVCFs. In vitro and in vivo tests further proved the possibility of improving the retrieval rates of RVCFs by effectively inhibiting vein endothelial proliferation, but the anticoagulation and antithrombosis effects of Heparin were unsatisfactory.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13


  1. 1.

    Sarosiek S, Crowther M, Sloan JM (2013) Indications, complications, and management of interior vena cava filters: the experience in 952 patients at an academic hospital with a level trauma center. J AMA Intern Med 173(7):513–517

  2. 2.

    Ray CE Jr, Mitchell E, Zipser S, Kao EY, Brown CF, Moneta GL (2006) Outcomes with retrievable inferior vena cava filters: a multicenter study. J Vasc Interv Radiol 17(10):1595–1604

  3. 3.

    Gaspard SF, Gaspard DJ (2009) Retrievable inferior vena cava filters are rarely removed. Am Surg 75(5):426–428

  4. 4.

    Doody O, Given MF, Kavnoudias H, Street M, Thomson KR, Lyon SM (2009) Initial experience in 115 patients with the retrievable Cook Celect vena cava filter. J Med Imaging Radiat Oncol 53(1):64–68

  5. 5.

    Zhou D, Spain J, Moon E, McLennan G, Sands MJ, Wang W (2012) Retrospective review of 120 celect inferior vena cava filter retrievals: experience at a single institution. J Vasc Interv Radiol 23(12):1557–1563

  6. 6.

    Minocha J, Idakoji I, Riaz A et al (2010) Improving inferior vena cava filter retrieval rates : impact of a dedicated inferior vena cava filter clinic. J Vasc Interv Radiol 21(12):1847–1851

  7. 7.

    Zhou D, Spain J et al (2012) Retrospective review of 120 celect inferior vena cava filter retrievals: experience at a single institution. J Vasc Interv Radiol 23(12):1557–1563

  8. 8.

    Ray CE Jr1, Mitchell E, et al. Outcomes with retrievable inferior vena cava filters: a multicenter study. J Vasc Interv Radiol 2006;17(10):1595-1604

  9. 9.

    Van Ha TG, Chien AS et al (2008) Use of retrievable compared to permanent inferior vena cava filters: a single-institution experience. Cardiovasc Intervent Radiol 31(2):308–315

  10. 10.

    Smouse HB, Rosenthal D, Thuong VH et al (2009) Long-term retrieval success rate profile for the Günther Tulip vena cava filter. J Vasc Interv Radiol 20(7):871–877

  11. 11.

    Rimon U, Volkov A, Garniek A et al (2009) Histology of tissue adherent to OptEase inferior vena cava filters regarding indwelling time. Cardiovasc Intervent Radiol 32(1):93–96

  12. 12.

    Lyon SM, Riojas GE, Uberoi R et al (2009) Short- and long-term retrievability of the Celect vena cava filter: results from a multi-institutional registry. J Vasc Interv Radiol 20(11):1441–1448

  13. 13.

    Zhou D, Spain J, Moon E et al (2012) Retrospective review of 120 Celect inferior vena cava filter retrievals: experience at a single institution. J Vasc Interv Radiol 23(12):1557–1563

  14. 14.

    Streiff MB (2000) Vena caval filters: a comprehensive review. [J]. Blood 95(12):3669–3677

  15. 15.

    Greenfield LJ, Proctor MC, Michaels AJ, Taheri PA et al (2000) Prophylactic vena caval filters in trauma: the rest of the story. J Vasc Surg 32(3):490–497

  16. 16.

    Neuerburg J, Günther R, Rassmussen E et al (1993) New retrievable percutaneous vena filter: experimental in vitro and vivo evolution. Cardiovasc Intervent Radiol 16(4):224–229

  17. 17.

    De Gregorio M, Gimeno M, Tobio R et al (2001) Animal experience in the Günther tulip retrievable inferior vena caval filter. Cardiovasc Intervent Radiol 24(6):413–417

  18. 18.

    Marx SO, Jayaraman T et al (1995) Rapamycin-FKBP inhibits cell cycle regulators of proliferation in vascular smooth muscle cells. Circ Res 76(3):412–417

  19. 19.

    Jayaraman T, Marks AR (1993) Rapamycin-FKBP12 blocks proliferation, induces differentiation, and inhibits cdc2 kinase activity in a myogenic cell line. J Biol Chem 34:25385–25388

  20. 20.

    Parry TJ, Brosius R et al (2005) Drug-eluting stents: sirolimus and paclitaxel differentially affect cultured cells and injured arteries. Eur J Phaimacol 524(1–3):19–29

  21. 21.

    Park YJ, Min SK et al (2015) Effect of imatinib mesylate and rapamycin on the preformed intimal hyperplasia in rat carotid injury model. Ann Surg Treat Res 88(3):152–159

  22. 22.

    Skalský I, Szárszoi O et al (2012) A perivascular system releasing sirolimus prevented intimal hyperplasia in a rabbit model in a medium-term study. Int J Pharm 427(2):311–319

  23. 23.

    Yu X, Takayama T et al (2014) A rapamycin-releasing perivascular polymeric sheath produces highly effective inhibition of intimal hyperplasia. J Control Release 191:47–53

  24. 24.

    De Gregorio MA, Gimeno MJ et al (2004) Retrievability of uncoated versus paclitaxel-coated Günther-Tulip IVC filters in an animal model. J Vasc Interv Radiol 15(7):719–726

  25. 25.

    Xiao L, Wang M (2013) MMPI drug-eluting IVC filter decreases adhesion between caval wall and filter. Cell Biochem Biophys 65(2):159–161

  26. 26.

    Sousa JE, Costa MA, Abizaid A et al (2001) Lack of neointimal proliferation after implantation of sirolimus-coated stents in human coronary arteries. Circulation 103(2):192–195

  27. 27.

    Moses JW, Leon MB, Popma JJ et al (2003) Sirolimus -eluting stents versus standard stents in patients with stenos is in a native coronary artery. N Engl J Med 349(14):1315–1323

  28. 28.

    Schofer J, Schluter M, Gershlick AH et al (2003) Sirolimus -eluting s tents for treatment of patients with long atherosclerotic les ions in small coronary arteries : double-blind, randomised controlled trial (E-SIRIUS). Lancet 362(9390):1093–1099

  29. 29.

    Serruys PW, van Hout B et al (1998) Randomised comparison of implantation of heparin-coated stents with balloon angioplasty in selected patients with coronary artery disease (Benestent II). Lancet 352(9129):673–681

  30. 30.

    Vrolix MC, Legrand VM et al (2000) Heparin-coated Wiktor stents in human coronary arteries (MENTOR Trial). Am J Cardiol 86(4):385–389

  31. 31.

    Prince MR, Novelline RA, Athanasonlis CA et al (1983) The diameter of the inferior vena cava and its implications for the use of vena caval filters. Radiology 149(3):687–689

Download references

Author information

Correspondence to Fuxian Zhang.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Zhao, H., Zhang, F., Liang, G. et al. Preparation and experimental research into retrievable rapamycin- and heparin-coated vena cava filters: a pilot study. J Thromb Thrombolysis 41, 422–432 (2016). https://doi.org/10.1007/s11239-015-1278-3

Download citation


  • Retrievable vena cava filter
  • Drug-coating
  • Rapamycin
  • Heparin