Inhaled Carbon Monoxide Prevents Graft-Induced Intimal Hyperplasia in Swine

Basel Ramlawi, Jeffrey R. Scott, Jun Feng, Shigetoshi Mieno, Kathleen G. Raman, David Gallo, Eva Csizmadia, Beek Yoke Chin, Fritz H. Bach, Leo E. Otterbein, Frank W. Sellke

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Background: Arteriovenous grafts often fail due to stenosis caused by venous anastomotic intimal hyperplasia (IH) and vascular smooth muscle cell (VSMC) proliferation. We examined the effects of inhaled carbon monoxide (CO), a product of heme-oxygenase-1 degradation of heme, on IH in a porcine arteriovenous graft model. Materials and methods: Eighteen Yorkshire pigs were divided into three groups (N = 6/group): (1) CO 100 ppm preoperatively for 1 h; (2) CO 250 ppm preoperatively for 1 h and intraoperatively; and (3) air-treated controls. Animals underwent end-to-side placement of polytetrafluoroethylene grafts connecting the common femoral artery and vein in both groins. Intimal thickness of the venous anastomosis at 30 days was measured blinded. The effect of CO on pig VSMC proliferation was studied in cell culture using [3H]thymidine incorporation. Results: Pigs in the group receiving CO 250 ppm showed significantly less IH compared to animals in the group receiving 100 ppm and the air-treated group (267.5 ± 21.4, 824 ± 145.8, and 914.8 ± 133.7 pixels, respectively, P < 0.0001). This effect was not observed when comparing the 100 ppm group to the air-treated group. COHb levels were significantly elevated in the 100 ppm and 250 ppm compared to air-treated pigs (5.8 ± 0.47, 13.2 ± 1.0 versus 2.3 ± 0.11%, respectively, P < 0.001). Oxygen saturation, respiratory rate, and hemodynamics were not significantly different between the groups. CO induced VSMC growth arrest compared to air in vitro (11.9 ± 4 versus 20.3 ± 5 103 counts/min/well, P < 0.01). Conclusion: A single exposure to a low concentration of inhaled CO (250 ppm) confers protection against intimal proliferation of VSMCs when given perioperatively in a clinically relevant model of arteriovenous grafts. These data are the first to suggest, in a clinically relevant model, the potential role for CO in clinical applications.

Original languageEnglish (US)
Pages (from-to)121-127
Number of pages7
JournalJournal of Surgical Research
Issue number1
StatePublished - Mar 2007


  • anastomosis
  • arteriovenous grafts
  • carbon monoxide
  • heme oxygenase-1
  • intimal hyperplasia
  • vascular smooth muscle proliferation

ASJC Scopus subject areas

  • Surgery


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