Topical cilostazol inhibits neointimal hyperplasia in a rat interposition vein graft model

Plast Reconstr Surg. 2014 Dec;134(6):895e-901e. doi: 10.1097/PRS.0000000000000730.


Background: Neointimal hyperplasia is a common cause of vein graft failure resulting from luminal narrowing and occlusion. Cilostazol is a U.S. Food and Drug Administration-approved phosphodiesterase III and platelet aggregation inhibitor commonly used in peripheral vascular disease. The authors studied whether topical cilostazol treatment at the time of vein grafting helps limit the development of neointimal hyperplasia in a rat model.

Methods: Six experimental rats and six control rats underwent interposition vein grafting into the femoral artery, followed by a single topical dose of cilostazol applied around the vein graft in the experimental animals. After 4 weeks, grafts were harvested and underwent histologic staining of axial sections to visualize intima thickness and elastin/myocyte content. Quantification was performed to assess total intima area. The intima-to-media and the intima-to-sum of intima and media ratios were determined to control for discrepancies in overall graft size.

Results: Cilostazol-treated grafts had a thinner intima layer with less myocyte content compared with control grafts, amounting to an 82 percent decrease in total intima area compared with controls. A similar trend was seen even after controlling for overall graft size, with 85 and 76 percent reductions seen in intima-to-media and intima-to-sum of intima and media ratios, respectively.

Conclusions: A single intraoperative dose of cilostazol applied locally significantly reduced intima size and smooth muscle content in rat interposition vein grafts examined 4 weeks postoperatively. A topical dose of cilostazol at surgery may therefore be helpful in controlling neointimal hyperplasia and reducing the need for systemic medications to prolong vein graft patency.

Publication types

  • Evaluation Study

MeSH terms

  • Administration, Topical
  • Animals
  • Cilostazol
  • Graft Occlusion, Vascular / etiology
  • Graft Occlusion, Vascular / prevention & control*
  • Hyperplasia / etiology
  • Hyperplasia / prevention & control
  • Neointima / complications
  • Neointima / pathology
  • Neointima / prevention & control*
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Tetrazoles / therapeutic use*
  • Treatment Outcome
  • Veins / pathology
  • Veins / transplantation*


  • Platelet Aggregation Inhibitors
  • Tetrazoles
  • Cilostazol