CardioVascular and Interventional Radiology

, Volume 36, Issue 5, pp 1364–1370 | Cite as

Is a Swine Model of Arteriovenous Malformation Suitable for Human Extracranial Arteriovenous Malformation? A Preliminary Study

  • Ming-ming LvEmail author
  • Xin-dong Fan
  • Li-xin Su
Laboratory Investigation



A chronic arteriovenous malformation (AVM) model using the swine retia mirabilia (RMB) was developed and compared with the human extracranial AVM (EAVM) both in hemodynamics and pathology, to see if this brain AVM model can be used as an EAVM model.


We created an arteriovenous fistula between the common carotid artery and the external jugular vein in eight animals by using end-to-end anastomosis. All animals were sacrificed 1 month after surgery, and the bilateral retia were obtained at autopsy and performed hematoxylin and eosin staining and immunohistochemistry. Pre- and postsurgical hemodynamic evaluations also were conducted. Then, the blood flow and histological changes of the animal model were compared with human EAVM.


The angiography after operation showed that the blood flow, like human EAVM, flowed from the feeding artery, via the nidus, drained to the draining vein. Microscopic examination showed dilated lumina and disrupted internal elastic lamina in both RMB of model and nidus of human EAVM, but the thickness of vessel wall had significant difference. Immunohistochemical reactivity for smooth muscle actin, angiopoietin 1, and angiopoietin 2 were similar in chronic model nidus microvessels and human EAVM, whereas vascular endothelial growth factor was significant difference between human EAVM and RMB of model.


The AVM model described here is similar to human EAVM in hemodynamics and immunohistochemical features, but there are still some differences in anatomy and pathogenetic mechanism. Further study is needed to evaluate the applicability and efficacy of this model.


Arteriovenous malformation Rete mirabile Animal model Immunohistochemistry 



This work was supported by National Natural Science Foundation of China (Grant No. 81071243).

Conflict of interest

The authors (Mingming Lv, Xindong Fan, Lixin Su) declare no conflicts of interest.


  1. 1.
    Buckmiller LM, Richter GT, Suen JY (2010) Diagnosis and management of hemangiomas and vascular malformations of the head and neck. Oral Dis 16(5):405–418PubMedCrossRefGoogle Scholar
  2. 2.
    Jahan R, Solberg TD, Lee D, Medin P, Tateshima S, De Salles A, Sayre J, Vinters HV, Viñuela F (2007) An arteriovenous malformation model for stereotactic radiosurgery research. Neurosurgery 61(1):152–159PubMedCrossRefGoogle Scholar
  3. 3.
    Isoda K, Fukuda H, Takamura N et al (1981) Arteriovenous malformation of the brain: histological study and micrometric measurement of abnormal vessel. Acta Pathol Jpn 31:883–931PubMedGoogle Scholar
  4. 4.
    Wu JK, Bisdorff A, Gelbert F et al (2005) Auricular arteriovenous malformation: evaluation, management, and outcome. Plast Reconstr Surg 115:985–995PubMedCrossRefGoogle Scholar
  5. 5.
    Laurian C (2011) Congenital arteriovenous malformations: what are the perspectives? Phlebolymphology 18(3):149–153Google Scholar
  6. 6.
    Kim JY, Kim DI, Do YS, Lee BB, Kim YW, Shin SW, Byun HS, Roh HG, Choo IW, Hyon WS, Shim JS, Choi JY (2006) Surgical treatment for congenital arteriovenous malformation: 10 years’ experience. Eur J Vasc Endovasc Surg 32:101–106PubMedCrossRefGoogle Scholar
  7. 7.
    Yakes WF, Rossi P, Odink H (1996) How I do it. Arteriovenous malformation management. Cardiovasc Intervent Radiol 19:65–71PubMedCrossRefGoogle Scholar
  8. 8.
    Chaloupka C, Vinuela F, Robert J et al (1994) An in vivo arteriovenous malformation model in swine: preliminary feasibility and natural history study. AJNR Am J Neuroradiol 15(5):945–950PubMedGoogle Scholar
  9. 9.
    Massoud TF, Ji C, Vinuela F et al (1994) An experimental arteriovenous malformation model in swine: anatomic basis and construction technique. AJNR Am J Neuroradiol 15:1537–1545PubMedGoogle Scholar
  10. 10.
    Murayama Y, Massoud TF, Viuela F (1998) Hemodynamic changes in arterial feeders and draining veins during embolotherapy of arteriovenous malformations: an experimental study in a swine model. Neurosurgery 43(1):96–104PubMedCrossRefGoogle Scholar
  11. 11.
    Kohout MP, Hansen M, Pribaz JJ et al (1998) Arteriovenous malformations of the head and neck: natural history and management. Plast Reconstr Surg 102:643–654PubMedGoogle Scholar
  12. 12.
    Zafirellis K, Agrogiannis G, Zachaki A, Gravani K, Karameris A, Kombouras C (2008) Prognostic significance of VEGF expression evaluated by quantitative immunohistochemical analysis in colorectal cancer. J Surg Res 147:99–107. doi: 10.1016/j.jss.2007.05.041 PubMedCrossRefGoogle Scholar
  13. 13.
    Xu Q, Zhang Z, Zhang P et al (2008) Antisense oligonucleotides and all-trans retinoic acid have a synergistic anti-tumor effect on oral squamous cell carcinoma. BMC Cancer 8:159. doi: 10.1186/1471-2407-8-159 PubMedCrossRefGoogle Scholar
  14. 14.
    Mandybur TI, Nazek M (1990) Cerebral arteriovenous malformations: a detailed morphological and immunohistochemical study using actin. Arch Pathol Lab Med 114:970–973PubMedGoogle Scholar
  15. 15.
    Young AE, Mulliken JB (1988) Arteriovenous malformations. In: Mulliken JB (ed) Vascular birthmarks: hemangiomas and malformations. WB Saunders, Philadelphia, pp 228–245Google Scholar
  16. 16.
    Holman E (1955) The physiology of an arteriovenous fistula. Am J Surg 89(6):1101 Full-text bibliographic links external resolver library holdingsPubMedCrossRefGoogle Scholar
  17. 17.
    Holman E (1968) Abnormal arteriovenous communications, 2nd edn. Charles C Thomas, SpringfieldGoogle Scholar
  18. 18.
    Folkman J, D’Amore PA (1996) Blood vessel formation: what is its molecular basis? Cell 87:1153–1155PubMedCrossRefGoogle Scholar
  19. 19.
    Ferrara N, Davis-Smyth T (1997) The biology of vascular endothelial growth factor. Endocr Rev 18:4–25PubMedCrossRefGoogle Scholar
  20. 20.
    Davis S, Aldrich TH, Jones PF et al (1996) Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning. Cell 87(7):1161–1169PubMedCrossRefGoogle Scholar
  21. 21.
    Suri C, Jones PF, Patan S et al (1996) Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell 87(7):1171–1180PubMedCrossRefGoogle Scholar
  22. 22.
    Dumont DJ, Gradwohl G, Fong GH et al (1994) Dominant negative and targeted null mutations in the endothelial receptor tyrosine kinase, tek, reveal a critical role in vasculogenesis of the embryo. Genes Dev 8:1897–1909PubMedCrossRefGoogle Scholar
  23. 23.
    Zhu Y, Lee C, Shen F et al (2005) Angiopoietin-2 facilitates vascular endothelial growth factor-induced angiogenesis in the mature mouse brain. Stroke 36:1533–1537PubMedCrossRefGoogle Scholar
  24. 24.
    Meijer-Jorna LB, van der Loos CM, Teeling P et al (2012) Proliferation and maturation of microvessels in arteriovenous malformations—expression patterns of angiogenic and cell cycle-dependent factors. J Cutan Pathol 39:610–620PubMedCrossRefGoogle Scholar
  25. 25.
    Thurston G, Rudge JS, Ioffe E et al (2000) Angiopoietin-1 protects the adult vasculature against plasma leakage. Nat Med 6:460–463PubMedCrossRefGoogle Scholar
  26. 26.
    Maisonpierre PC, Suri C, Jones PF et al (1997) Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 277(5322):55–60PubMedCrossRefGoogle Scholar
  27. 27.
    Asahara T, Chen D, Takahashi T et al (1998) Tie2 receptor ligands, angiopoietin-1 and angiopoietin-2, modulate VEGF-induced postnatal neovascularization. Circ Res 83(3):233–240PubMedCrossRefGoogle Scholar
  28. 28.
    Fiedler U, Augustin HG (2006) Angiopoietins: a link between angiogenesis and inflammation. Trends Immunol 27(12):552–558PubMedCrossRefGoogle Scholar
  29. 29.
    Ferrara N, Henzel WJ (1989) Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun 161:851–858PubMedCrossRefGoogle Scholar
  30. 30.
    Gerber HP, Dixit V, Ferrara N (1998) Vascular endothelial growth factor induces expression of the antiapoptotic proteins. Bcl-2 and A1 in vascular endothelial cells. J Biol Chem 273:13313–13316PubMedCrossRefGoogle Scholar
  31. 31.
    Alon T, Hemo I, Itin A et al (1995) Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity. Nat Med 1:1024–1028PubMedCrossRefGoogle Scholar
  32. 32.
    Suhantja A, Hofman H (2003) Role of growth factors and their receptors in proliferation of microvascular endothelial cell. Microsc Res Tech 60(1):70–77CrossRefGoogle Scholar
  33. 33.
    Zheng LZ, Fan XD, Zheng JW et al (2009) Ethanol embolization of auricular arteriovenous malformations: preliminary results of 17 cases. AJNR Am J Neuroradiol 30:1679–1684PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2013

Authors and Affiliations

  1. 1.Department of Oral & Maxillofacial Surgery, Shanghai Key Laboratory of StomatologyNinth People’s Hospital, Shanghai Jiao Tong University School of MedicineShanghaiPeople’s Republic of China
  2. 2.Department of RadiologyNinth People’s Hospital, Shanghai Jiao Tong University School of MedicineShanghaiPeople’s Republic of China

Personalised recommendations