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Therapeutic site selection is important for the successful development of collateral vessels  Ayako Nishiyama, MD, PhD, Hiroyuki Koyama, MD, PhD, Tetsuro.

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Presentation on theme: "Therapeutic site selection is important for the successful development of collateral vessels  Ayako Nishiyama, MD, PhD, Hiroyuki Koyama, MD, PhD, Tetsuro."— Presentation transcript:

1 Therapeutic site selection is important for the successful development of collateral vessels 
Ayako Nishiyama, MD, PhD, Hiroyuki Koyama, MD, PhD, Tetsuro Miyata, MD, PhD, Toshiaki Watanabe, MD, PhD  Journal of Vascular Surgery  Volume 62, Issue 1, Pages (July 2015) DOI: /j.jvs Copyright © 2015 Society for Vascular Surgery Terms and Conditions

2 Fig 1 The anatomic pattern of collateral development in the rabbit model of limb ischemia was analyzed by aortic injection of a lead oxide solution at 28 days after excision of the left femoral artery. a, Aortic angiogram. Collateral vessels (open arrowheads) developed between the left posterior gluteal artery and the left popliteal artery. b, Photograph showing orange collateral vessels (open arrowheads) in the coccygeofemoral muscle. Note that collateral vessels are considerably larger than the right posterior gluteal artery (closed arrowheads). c, Schematic diagram of arterial anatomy in the coccygeofemoral muscle of the rabbit model. d, Schematic diagram of arterial anatomy in the adductor muscle of the rabbit model. Animals in all images are in the prone position. *Developed collateral artery. †Total removal of the left femoral artery. ‡Normal size branch of posterior gluteal artery. §Normal size branch of deep femoral artery. **The branch of the deep femoral artery whose blood flow was lost by femoral artery removal. FA (red asterisk), Femoral artery; PA, popliteal artery; IIA (yellow arrow), internal iliac artery. Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2015 Society for Vascular Surgery Terms and Conditions

3 Fig 2 a, Calf blood pressure ratio before basic fibroblast growth factor/phosphate-buffered saline (bFGF/PBS) injection and at 28 days after the injection. b, Resting blood flow and maximum blood flow of the left internal iliac artery at 28 days after the injection. a-c, Selective internal iliac angiograms at 28 days after bFGF/PBS injection: c, coccygeo group; d, adductor group; e, vehicle group. f, Angiographic score. *P < .01 (vs other groups). †P < .05. Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2015 Society for Vascular Surgery Terms and Conditions

4 Fig 3 Immunohistologic images of coccygeofemoral muscle at 3 days after basic fibroblast growth factor/phosphate-buffered saline (bFGF/PBS) injection. Immunostaining for Ki-67 (a-c), monocyte chemotactic protein 1 (MCP-1) (d-f), and fibroblast growth factor receptor 1 (FGFR-1) (g-i): a, d, and g, coccygeo group; b, e, and h, adductor group; c, f, and i, vehicle group. Antigen-positive parts were stained brown; arrowheads also indicate stained parts. Bar, 100 μm. To quantify the immunostaining results, the densities of Ki-67-positive cells (j), MCP-1-positive cells (k), and FGFR-1-positive vessels (l) were calculated. *P < .01 (vs other groups at 3 days). Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2015 Society for Vascular Surgery Terms and Conditions

5 Fig 4 a-c, Microphotographs of coccygeofemoral muscle at 14 days after basic fibroblast growth factor/phosphate-buffered saline (bFGF/PBS) injection: a, Coccygeo group; b, adductor group; c, vehicle group. The sections were stained by hematoxylin and eosin. Bar, 200 μm. To quantitatively analyze collateral development, the density (d) and wall thickness (e) of arteries were calculated. *P < .01. †P < .05 (vs other groups). Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2015 Society for Vascular Surgery Terms and Conditions

6 Fig 5 a, Fibroblast growth factor receptor 1 (FRFR-1) expression and phosphorylation in coccygeofemoral muscle at 3 and 7 days after basic fibroblast growth factor/phosphate-buffered saline (bFGF/PBS) injection. FGFR-1 in each muscle lysate was recovered by immunoprecipitation (IP) and analyzed by Western blotting (WB) with an antibody against FGFR-1 (top) or phosphorylated tyrosine (bottom). b, bFGF expression in coccygeofemoral muscle at 3 and 7 days after injection. bFGF in each lysate was concentrated with heparin-Sepharose and analyzed by Western blotting with an antibody for bFGF. C, Coccygeo group; A, adductor group, V, vehicle group. Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2015 Society for Vascular Surgery Terms and Conditions

7 Fig 6 Therapeutic site for effective collateral development in the rabbit model of limb ischemia. a, The coccygeofemoral muscle receives dominant perfusion through the posterior gluteal artery and minor perfusion through the popliteal artery, and arteriolar connections exist between the distal branches of the two feeding arteries. When the feeding arteries function adequately, the arteriolar connections do not perform an important role. b, Removal of the femoral artery induced limb ischemia, and then the arteriolar connections in the coccygeofemoral muscle developed into collateral vessels. If the maturation of the arteriolar connections is insufficient, the limb develops chronic ischemia. Thus, the immature arteriolar connection might be a therapeutic site in this model. c, The enlargement and maturation of arterioles are promoted by the process of arteriogenesis, and basic fibroblast growth factor (bFGF) is a potent inducer of arteriogenesis. Selective delivery of bFGF (closed squares) to the arteriolar connection markedly enhanced collateral development and limb perfusion. *Arteriolar connections. **Premature collateral arteries. †Developed collateral arteries. ††Total removal of the left femoral artery. IIA, Internal iliac artery; FA, femoral artery; PA, popliteal artery. Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2015 Society for Vascular Surgery Terms and Conditions


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