title: Suppression of postoperative intimal hyperplasia of vein grafts with edaravone in rat models - a scanning electron microscope study.
abstract: OBJECTIVE
  Postoperative intimal hyperplasia, the most common cause of vein graft occlusion, is initiated by endothelial injury. In the present study, the mechanism by which the free radical scavenger edaravone (Radicut, Mitsubishi Tanabe Pharma Co, Japan) protects against endothelial injury in postoperative intimal hyperplasia was investigated.
  
  
  METHODS
  In 18 male Lewis rats, a right epigastric vein graft was interposed into the common femoral artery. Nine rats received a pre-operative intraperitoneal administration of edaravone (3.0 mg/kg, edaravone group) and the other nine rats received an equal volume of saline (saline group). After 1 h, five vein grafts from each group were treated with Verhoeff-van Gieson elastica stain and subjected to a histological examination. The other four vein grafts from each group were examined with an S-800 Hitachi scanning electron microscope (SEM) (Hitachi High-Technologies Co, Japan) at ×1000 magnification, as were three unoperated right epigastric veins (unoperated vein group). The endothelial areas of the vein grafts were measured using computerized planimetry of the SEM images (ImageJ version 1.37, National Institutes of Health, USA). The mean endothelial areas (%) were compared between the two groups.
  
  
  RESULTS
  Verhoeff-van Gieson elastica stain revealed no significant differences between the two groups. SEM showed that endothelial cells in the unoperated epigastric vein had a cobblestone-like appearance. In the saline group, the endothelial cells were comb-shaped and had adherent monocytes. In the edaravone group, however, the cobblestone-like appearance of endothelial cells was well preserved, with little monocyte adhesion. Moreover, the mean (± standard error of the mean) endothelial area was significantly higher in vein grafts from the edaravone group than in those from the saline group (74±1.8% versus 56±4.3%, P<0.05), and was similar to those in the unoperated epigastric veins (72±1.9%).
  
  
  CONCLUSIONS
  These findings show that endothelial injury is present soon after placement of the interposition graft. The authors believe that edaravone suppresses postoperative intimal hyperplasia by alleviating endothelial injury.
authors.affiliation: Department of Cardiovascular Surgery, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yamamura
authors.forename: Yuji
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: Masataka
authors.initials: M
authors.lastname: Mitsuno
authors.forename: Hiroe
authors.initials: H
authors.lastname: Tanaka
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ryomoto