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Contrast-enhanced sonothrombolysis in a porcine model of acute peripheral arterial thrombosis and prevention of anaphylactic shock

Lab Animal volume 43, pages 91–94 (2014)Cite this article

Abstract

Acute peripheral arterial thrombosis can be threatening to life and limb. Dissolution of the thrombus local catheter-directed intra-arterial infusion of fibrinolytic agents such as urokinase is the standard therapy for thrombosis; however, this method is time-intensive, and amputation of the affected limb is still needed in 10–30% of cases. Furthermore, thrombolytic therapy carries the risk of bleeding complications. The use of small gas-filled bubbles, or ultrasound contrast agents (UCAs), in combination with ultrasound has been investigated as an improved thrombolytic therapy in acute coronary and cerebral arterial thrombosis. The authors describe a porcine model of acute peripheral arterial occlusion to test contrast-enhanced sonothrombolysis approaches that combine ultrasound, UCAs and fibrinolytic agents and recommend a strategy for preventing severe allergic reactions to UCAs in the pigs.

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Figure 1: Diagram of the iliac artery.

References

  1. Henke, P.K. Contemporary management of acute limb ischemia: factors associated with amputation and in-hospital mortality. Semin. Vasc. Surg. 22, 34–40 (2009).

    Article  Google Scholar 

  2. Creager, M.A., Kaufman, J.A. & Conte, M.S. Clinical practice. Acute limb ischemia. N. Engl. J. Med. 366, 2198–2206 (2012).

    Article  CAS  Google Scholar 

  3. Siegel, R.J. et al. Noninvasive transcutaneous low frequency ultrasound enhances thrombolysis in peripheral and coronary arteries. Echocardiography 18, 247–257 (2001).

    Article  CAS  Google Scholar 

  4. Alexandrov, A.V. et al. Ultrasound-enhanced systemic thrombolysis for acute ischemic stroke. N. Engl. J. Med. 351, 2170–2178 (2004).

    Article  CAS  Google Scholar 

  5. Culp, W.C. et al. Intracranial clot lysis with intravenous microbubbles and transcranial ultrasound in swine. Stroke 35, 2407–2411 (2004).

    Article  Google Scholar 

  6. Molina, C.A. et al. Microbubble administration accelerates clot lysis during continuous 2-MHz ultrasound monitoring in stroke patients treated with intravenous tissue plasminogen activator. Stroke 37, 425–429 (2006).

    Article  CAS  Google Scholar 

  7. Xie, F. et al. Treatment of acute intravascular thrombi with diagnostic ultrasound and intravenous microbubbles. JACC Cardiovasc. Imaging 2, 511–518 (2009).

    Article  Google Scholar 

  8. Marmottant, P. & Hilgenfeldt, S. Controlled vesicle deformation and lysis by single oscillating bubbles. Nature 423, 153–156 (2003).

    Article  CAS  Google Scholar 

  9. Hitchcock, K.E. & Holland, C.K. Ultrasound-assisted thrombolysis for stroke therapy: better thrombus break-up with bubbles. Stroke 41, S50–S53 (2010).

    Article  Google Scholar 

  10. Napoli, C. et al. In vivo veritas: thrombosis mechanisms in animal models. Scand. J. Clin. Lab. Invest. 66, 407–428 (2006).

    Article  CAS  Google Scholar 

  11. Kesava, P., Graves, V., Salamat, S. & Rappe, A. Intraarterial thrombolysis in a pig model: a preliminary note. AJNR Am. J. Neuroradiol. 18, 915–920 (1997).

    CAS  PubMed  Google Scholar 

  12. Szebeni, J. et al. Hemodynamic changes induced by liposomes and liposome-encapsulated hemoglobin in pigs: a model for pseudoallergic cardiopulmonary reactions to liposomes. Role of complement and inhibition by soluble CR1 and anti-C5 a antibody. Circulation 99, 2302–2309 (1999).

    Article  CAS  Google Scholar 

  13. Krause, W., Gerlach, S. & Muschick, P. Prevention of the hemodynamic effects of iopromide-carrying liposomes in rats and pigs. Invest. Radiol. 35, 493–503 (2000).

    Article  CAS  Google Scholar 

  14. Szebeni, J. et al. A porcine model of complement-mediated infusion reactions to drug carrier nanosystems and other medicines. Adv. Drug Deliv. Rev. 64, 1706–1716 (2012).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Surgery, VU University Medical Center, Amsterdam, The Netherlands

    Johanna H. Nederhoed,  Willem Wisselink &  Kak K. Yeung

  2. Department of Cardiology, VU University Medical Center, Amsterdam, The Netherlands

    Jeroen Slikkerveer

  3. Amsterdam Animal Research Center, VU University Medical Center, Amsterdam, The Netherlands

    Klaas W. Meyer

  4. Department of Physiology, VU University Medical Center, Amsterdam, The Netherlands

    René J.P. Musters &  Kak K. Yeung

Authors
  1. Johanna H. Nederhoed
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  2. Jeroen Slikkerveer
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  3. Klaas W. Meyer
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  4. René J.P. Musters
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  5. Kak K. Yeung
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Corresponding author

Correspondence to Johanna H. Nederhoed.

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The authors declare no competing financial interests.

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Nederhoed, J., Slikkerveer, J., Meyer, K. et al. Contrast-enhanced sonothrombolysis in a porcine model of acute peripheral arterial thrombosis and prevention of anaphylactic shock. Lab Anim 43, 91–94 (2014). https://doi.org/10.1038/laban.438

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