Ann Surg Treat Res.  2017 Feb;92(2):97-104. 10.4174/astr.2017.92.2.97.

Inhibitory effect of sustained perivascular delivery of paclitaxel on neointimal hyperplasia in the jugular vein after open cutdown central venous catheter placement in rats

Affiliations
  • 1Department of General Surgery, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea.
  • 2Department of Surgery, Kangwon National University School of Medicine, Chuncheon, Korea. sukbae75.moon@gmail.com
  • 3Department of Surgery, Eulji University Hospital, Daejeon, Korea.

Abstract

PURPOSE
Inhibitory effect of paclitaxel on neointimal hyperplasia after open cutdown has not been elucidated.
METHODS
For the control group (n = 16), silicone 2.7-Fr catheters were placed via the right external jugular vein with the cutdown method. For the treatment group (n = 16), a mixture of 0.65 mg of paclitaxel and 1 mL of fibrin glue was infiltrated around the exposed vein after cutdown. After scheduled intervals (1, 2, 4, and 8 weeks), the vein segment was harvested and morphometric analysis was performed on cross-sections.
RESULTS
Proliferation of smooth muscle cell (SMC) was strongly suppressed in the treatment group, and the ratio of neointima to vein wall was significantly reduced in the treatment group (8 weeks; 0.63 ± 0.08 vs. 0.2 ± 0.08, P < 0.05). Luminal patency was significantly more preserved in the treatment group, and the luminal area was significantly wider in the paclitaxel-treated group compared to the control group (8 weeks; 1.91 ± 0.43 mm² vs. 5.1 ± 0.43 mm², P < 0.05). Mean SMC counts measured at 1 and 2 weeks after cutdown were significantly lower in the treatment group (2 weeks; 115 ± 22 vs. 62 ± 22). Paclitaxel was undetectable in systemic circulation (<10 ng/mL).
CONCLUSION
Sustained perivascular delivery of paclitaxel with fibrin glue was effective in inhibiting neointimal hyperplasia in rat jugular vein after open cutdown.

Keyword

Paclitaxel; Neointima; Central venous catheters; Fibrin; Jugular veins

MeSH Terms

Animals
Catheters
Central Venous Catheters*
Fibrin
Fibrin Tissue Adhesive
Hyperplasia*
Jugular Veins*
Methods
Myocytes, Smooth Muscle
Neointima
Paclitaxel*
Phenobarbital
Rats*
Silicon
Silicones
Veins
Fibrin
Fibrin Tissue Adhesive
Paclitaxel
Phenobarbital
Silicon
Silicones

Figure

  • Fig. 1 Delineation of neointimal hyperplasia (arrow) at 1 and 2 weeks postoperatively (PO) following cutdown central venous catheter placement against whole vein wall (arrowhead). Neointimal hyperplasia was consistently thicker in the control group than in the treatment group (H&E, ×40). (A) Control group, 1 week PO, (B) paclitaxel treatment group, 1 week PO, (C) control group, 2 weeks PO, and (D) paclitaxel treatment group, 2 weeks PO.

  • Fig. 2 Neointimal hyperplasia index was significantly lower in the treatment group.

  • Fig. 3 (A, B) Measurement of luminal area at 8 weeks postoperatively (H&E ×40). Measured patent luminal area was larger in the treatment group than in the control group.

  • Fig. 4 Patent luminal area was significantly wider in the treatment group than in the control group at each measured interval in the observation period.

  • Fig. 5 Smooth muscle cell (SMC) counts in the early postoperative phases (1 and 2 weeks) measured on high-powered fields (×600) with immunohistochemical staining. SMC counts were reduced in the treatment group compared to those in the control group. (A) Control group, 1 week PO, (B) paclitaxel treatment group, 1 week PO, (C) control group, 2 weeks PO, and (D) paclitaxel treatment group, of 2 weeks PO.

  • Fig. 6 Mean smooth muscle cell (SMC) counts were significantly lower in the treatment group than in the control group at 1 and 2 weeks postoperatively.


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