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Continuous periaortic infusion improves doxycycline efficacy in experimental aortic aneurysms  Eiketsu Sho, PhD, Jack Chu, PhD, Mien Sho, MD, Brian Fernandes,

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Presentation on theme: "Continuous periaortic infusion improves doxycycline efficacy in experimental aortic aneurysms  Eiketsu Sho, PhD, Jack Chu, PhD, Mien Sho, MD, Brian Fernandes,"— Presentation transcript:

1 Continuous periaortic infusion improves doxycycline efficacy in experimental aortic aneurysms 
Eiketsu Sho, PhD, Jack Chu, PhD, Mien Sho, MD, Brian Fernandes, PhD, Diane Judd, BS, Prema Ganesan, BS, Hideo Kimura, PhD, Ronald L Dalman, MD  Journal of Vascular Surgery  Volume 39, Issue 6, Pages (June 2004) DOI: /j.jvs

2 Fig 1 PDS. The PE-10 tubing is placed adjacent to the aorta immediately after intraluminal elastase infusion, wrapped with polyvinyl alcohol foam, and tunneled across the abdominal wall to connect with a reservoir containing either doxycycline solution or vehicle alone (representative photograph). Journal of Vascular Surgery  , DOI: ( /j.jvs )

3 Fig 2 Infusion-related endothelial, smooth muscle, and lamellar injury as a function of PPE dose and infusion time. (i) Hematoxylin-eosin stain; (ii) aortic elastin autofluorescence, both original magnification ×400. Journal of Vascular Surgery  , DOI: ( /j.jvs )

4 Fig 3 Effect of doxycycline treatment status on elastin preservation. AAA diameter (i, original magnification 4×) was reduced with either twice-daily subcutaneous injections (SC-DOX, 60 mg/kg/day) or continuous periaortic infusion (PDS-DOX, 1.5 mg/kg/day) doxycycline therapy. SC-CON, AAA treated with vehicle alone. ii, Medial elastic lamellar attenuation as a function of doxycycline treatment status (arrowheads). Proliferating SMCs are present on the luminal side of the degenerating media surrounded by newly synthesized elastin fibers (original magnification ×400; elastin Masson trichrome stain). Journal of Vascular Surgery  , DOI: ( /j.jvs )

5 Fig 4 Effect of doxycycline treatment status on transmural macrophage density. (i) Doxycycline treatment; (ii) saline treatment; (iii) index of macrophage medial infiltration. Brown nuclei, ED-1 positive cells; CSA, cross-sectional area of media. *P < .01 vs doxycycline treatment group. Original magnification ×400. Journal of Vascular Surgery  , DOI: ( /j.jvs )

6 Fig 5 Effect of doxycycline treatment status on aortic SMC proliferation. Arrows, BrdU-labeled SMC nuclei in the actively remodeling aortic wall after PPE infusion. i, AAA after doxycycline treatment; ii, AAA after saline treatment (original magnification ×400); iii, index of BrdU-labeled SMCs in AAA wall. CSA, Cross-sectional area of media; *P < .01 vs doxycycline treatment group. Journal of Vascular Surgery  , DOI: ( /j.jvs )

7 Fig 6 MMP gene expression and activity in AAA tissue with or without doxycycline treatment. Doxycycline therapy reduced AAA MMP-9 gene expression in PDS-DOX group (A) and SC-DOX group (B), but it did not affect MMP-2 and -14 or TIMP-1 and -2. Gelatin gel zymography demonstrated reduced activity of pro- and active forms of MMP-9 after doxycycline treatment (C-F). The PDS method was more effective in this regard than subcutaneous injection (G). MMP-2 activity was not affected by doxycycline treatment. Lytic bands corresponding to apparent molecular weight (MW) of MMP-2 and MMP-9 were quantified by densitometry. *P < .01 vs doxycycline treatment; †P < .05 vs PDS-DOX group. Journal of Vascular Surgery  , DOI: ( /j.jvs )

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