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Related Experiment Videos

Continuous periaortic infusion improves doxycycline efficacy in experimental aortic aneurysms.

Eiketsu Sho1, Jack Chu, Mien Sho

  • 1Division of Vascular Surgery, Stanford University, Palo Alto, CA 94304, USA.

Journal of Vascular Surgery
|June 12, 2004
PubMed
Summary

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A novel continuous infusion system for juxta-aortic doxycycline delivery effectively reduced abdominal aortic aneurysm (AAA) diameter in animal models, offering a promising transitional step for hybrid drug/device therapies.

Area of Science:

  • Vascular Surgery
  • Pharmacology
  • Biomedical Engineering

Background:

  • Abdominal aortic aneurysm (AAA) disease poses significant clinical challenges.
  • Current endovascular AAA exclusion methods have limitations, including potential for late graft failure due to continued aneurysm wall activity.
  • Hybrid drug/device strategies are being explored to improve AAA treatment outcomes.

Purpose of the Study:

  • To develop and evaluate a novel continuous infusion system for juxta-aortic doxycycline delivery.
  • To assess the efficacy of this system as a transitional step toward hybrid drug/device treatment strategies for AAA.
  • To compare continuous periaortic delivery with traditional subcutaneous injection of doxycycline in an AAA animal model.

Main Methods:

  • Development of a periaortic delivery system (PDS) for continuous doxycycline infusion.

Related Experiment Videos

  • Creation of rat AAA models using porcine pancreatic elastase (PPE) infusion.
  • Comparison of PDS doxycycline delivery (1.5 mg/kg/day) versus subcutaneous injection (60 mg/kg/day) and vehicle controls.
  • Analysis of AAA diameter, medial elastin preservation, smooth muscle cell (SMC) proliferation, macrophage density, matrix metalloproteinase (MMP) expression, and serum drug levels.

    • Main Results:

    • Both PDS and subcutaneous doxycycline delivery achieved comparable reductions in AAA diameter over 14 days.
    • PDS delivery resulted in greater weight gain and potentially reduced systemic toxicity compared to subcutaneous injections.
    • Doxycycline treatment significantly reduced AAA macrophage infiltration and SMC proliferation, although elastic lamellar preservation was not observed.

    Conclusions:

    • Continuous periaortic doxycycline infusion effectively lowers the required dose for experimental AAA limitation.
    • This delivery method may enhance the clinical outcomes of minimally invasive AAA treatments.
    • The developed PDS serves as a prototype for adjuvant therapies complementing endovascular AAA exclusion, potentially stabilizing the aneurysm wall and improving long-term patient outcomes.