title: Supplemental oxygen reduces intimal hyperplasia after intraarterial stenting in the rabbit.
abstract: OBJECTIVE
  Supplemental oxygen can reduce intimal hyperplasia (IH) after stent deployment in a rabbit model.
  
  
  BACKGROUND
  Endovascular stent placement is technically feasible, but long-term durability in vessels outside the aortoiliac system is compromised with postinterventional IH, which causes restenosis and failure of the arterial conduit.
  
  
  METHODS
  Groups (n = 4 to 6) of female New Zealand white rabbits underwent placement of a 3-mm intraaortic stent with laparotomy and were placed in either normoxic (21% inspired oxygen concentration) or supplemental-oxygen (40% inspired oxygen concentration) environments for 0, 7, 14, and 28 days. The transarterial wall oxygen gradient was measured at 0, 7, and 28 days with an oxygen microelectrode. 5-Bromo-2'deoxyuridine (BrdU) was injected into the peritoneum before death to assess cellular proliferation. Aortic specimens were harvested en bloc and sectioned for analysis of cellular proliferation and intimal thickness.
  
  
  RESULTS
  Intraaortic stent placement significantly decreased the transarterial wall oxygen gradient in the outer 70% of the vessel wall and was easily reversed at 7, 14, and 28 days with application of supplemental oxygen. Cellular proliferation was significantly decreased at 14 days (0.5% +/- 0.001% versus 2.3% +/- 0.002%; P <.001) and 28 days (0.4% +/- 0.001% versus 1.0% +/- 0.001%; P <.025) as measured with count of nuclei staining for 5-Bromo-2'deoxyuridine in the intima and media. Intimal thickness was significantly decreased at 28 days in oxygen-supplemented rabbits (intimal area/medial area = 0.50 +/- 0.07) as compared with controls (intimal area/medial area = 0.89 +/- 0.11; P <.025).
  
  
  CONCLUSIONS
  This study shows the ability of supplemental oxygen to reverse arterial wall hypoxia, decrease cellular proliferation, and control IH at the deployment site of an intraarterial stent in a rabbit model. Forty-percent supplemental oxygen suppresses IH by 44% at 28 days as compared with normoxic control values. Cellular proliferation is reduced four-fold at 14 days and two-fold at 28 days in oxygen-supplemented rabbits as compared with control media after deployment. The clinical implications of these findings are significant, especially as the role of endovascular interventions continues to expand.
authors.affiliation: Department of Surgery, Minneapolis VA Medical Center, One Veterans Drive (112K), Minneapolis, MN 55417, USA. treti007@tc.umn.edu
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Tretinyak
authors.forename: Eugene S
authors.initials: ES
authors.lastname: Lee
authors.forename: Kristina M
authors.initials: KM
authors.lastname: Uema
authors.forename: Alexandre C
authors.initials: AC
authors.lastname: d'Audiffret
authors.forename: Michael P
authors.initials: MP
authors.lastname: Caldwell
authors.forename: Steven M
authors.initials: SM
authors.lastname: Santilli
mesh_terms: D000818:Animals; D019917:Blood Vessel Prosthesis Implantation / Q000009:adverse effects*; D004195:Disease Models, Animal; D005260:Female; D006083:Graft Occlusion, Vascular / Q000473:pathology / Q000517:prevention & control*; D006965:Hyperplasia / Q000209:etiology* / Q000473:pathology / Q000628:therapy*; D010102:Oxygen Inhalation Therapy; D011817:Rabbits; D015607:Stents / Q000009:adverse effects*; D013997:Time Factors; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology*