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Invited Commentary| Volume 63, ISSUE 4, P631, April 2022

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Endovascular Today: One Step Forward in Modelling Venous Thrombosis

Published:February 01, 2022DOI:https://doi.org/10.1016/j.ejvs.2021.12.023
      Schwein and co-authors described a scientifically elegant porcine model of deep vein thrombosis (DVT) that employs a transient three balloon occlusion of the bi-iliocaval segment followed by administration of thrombin into the occluded segment.
      • Schwein A.
      • Magnus L.
      • Markovits J.
      • Chinnadurai P.
      • Autry K.
      • Jenkins L.
      • et al.
      Endovascular porcine model of iliocaval venous thrombosis.
      Large animal models are crucial as an effective model for DVT in humans, as they differ less in anatomy and physiology than smaller animals. The first endovascular large animal models of venous thrombosis (VT) were described two decades ago.
      • Lin P.H.
      • Chen C.
      • Surowiec S.M.
      • Conklin B.
      • Bush R.L.
      • Lumsden A.B.
      Evaluation of thrombolysis in a porcine model of chronic deep venous thrombosis: an endovascular model.
      The major advantage of the novel model is the preservation of the structural integrity of the vein wall and the endothelial lining. The model attempts to resemble proximal human DVT, allows dynamic non-invasive visualisation, and enables experimental endovascular interventions. Bilateral thrombosis provides a valuable feature to compare the experimental intervention side with the contralateral non-intervention control side in the same animal. Hence, the model represents an attractive translation tool between the hybrid operating room and the laboratory.
      The authors successfully triggered thrombosis by activation of coagulation in a venous segment nearly excluded from the circulation. However, it is important to realise that DVT is mainly a local process facilitated by various systemic and regional factors. Endothelial re-programming to pro-thrombotic, antifibrinolytic, and pro-inflammatory phenotype remains the principal local mechanism. Both stasis and thrombin exposure have been shown to activate endothelial cells.
      • Minami T.
      • Sugiyama A.
      • Wu S.Q.
      • Abid R.
      • Kodama T.
      • Aird W.C.
      Thrombin and phenotypic modulation of the endothelium.
      ,
      • Zhou J.
      • May L.
      • Liao P.
      • Gross P.L.
      • Weitz J.I.
      Inferior vena cava ligation rapidly induces tissue factor expression and venous thrombosis in rats.
      Preservation of endothelial cells in the described model is one more step forward in excelling endovascular DVT modelling. It is critical to maintain and further investigate endothelial function during initiation, propagation, and resolution of DVT; as well as to dissect the immediate and long term endothelial response to various endovascular procedures.
      None of the current animal VT models can completely replicate the whole complexity of the human disease. The Holy Grail of VT modelling implies an altered (but still present) endothelial function, changed venous blood flow pattern, and activated coagulation. The main limitation of the described model is the absence of flow, which is unnatural compared with DVT in humans that initiates and propagates, at least during the initial stages, under blood flow conditions. The model does not aim to investigate non-occlusive, unilateral, and distal thrombosis. Any novel approach in the modelling arena must be externally validated, and we appreciate the authors for carefully describing the methodology in detail and cautioning about the learning curve. We applaud this large pre-clinical model, facilitating research and development of endovascular techniques for the deep venous system. We congratulate the authors and highly appreciate their efforts to promote basic and translational science in the field of venous disease.

      References

        • Schwein A.
        • Magnus L.
        • Markovits J.
        • Chinnadurai P.
        • Autry K.
        • Jenkins L.
        • et al.
        Endovascular porcine model of iliocaval venous thrombosis.
        Eur J Vasc Endovasc Surg. 2022; 63: 623-630
        • Lin P.H.
        • Chen C.
        • Surowiec S.M.
        • Conklin B.
        • Bush R.L.
        • Lumsden A.B.
        Evaluation of thrombolysis in a porcine model of chronic deep venous thrombosis: an endovascular model.
        J Vasc Surg. 2001; 33: 621-627
        • Minami T.
        • Sugiyama A.
        • Wu S.Q.
        • Abid R.
        • Kodama T.
        • Aird W.C.
        Thrombin and phenotypic modulation of the endothelium.
        Arterioscler Thromb Vasc Biol. 2004; 24: 41-53
        • Zhou J.
        • May L.
        • Liao P.
        • Gross P.L.
        • Weitz J.I.
        Inferior vena cava ligation rapidly induces tissue factor expression and venous thrombosis in rats.
        Arterioscler Thromb Vasc Biol. 2009; 29: 863-869

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