The role of short-term oxygen administration in the prevention of intimal hyperplasia

Authors

Charu Lata, Derrick Green, Jing Wan, Sabita Roy, Steven M. Santilli

Abstract

Intimal hyperplasia (IH) is the cause of most failed arteriovenous fistulas (AVFs), resulting in repeat procedures and leading to increased utilization of scarce health care resources. Our laboratory has previously demonstrated the role of supplemental oxygen in preventing IH and smooth muscle cell proliferation (SMCp) at an artery-to-graft anastomosis and at the deployment site of an intra-arterial stent. This study examines the effect of supplemental oxygen in preventing IH and SMCp in an AVF in a rabbit model. Ninety-six rabbits were randomized into four groups: group 1, control; group 2, no surgery with supplemental oxygen; group 3, AVF without supplemental oxygen; and group 4, AVF with supplemental oxygen. Rabbits receiving supplemental oxygen received 30% oxygen for up to 42 days. Specimens were collected in all groups at days 1, 3, 7, 21, 42, and 90. IH and SMCp were measured at the AVF site as well as in the artery and vein proximal and distal to the AVF. IH was first noted at day 7 and significantly increased through day 90 at all locations in the nonoxygen-supplemented groups. No significant IH was noted in the oxygen-supplemented group at any location or any time point. SMCp was noted at day 3 through day 21 in the nonoxygen-supplemented group, whereas almost no SMCp was noted in the oxygen-supplemented group at any location or time point. Without oxygen supplementation, SMCp begins at day 3 and is no longer noted at day 21 after creation of an AVF, whereas IH begins by day 7 and increases at least through day 90 after creation of an AVF. Forty-two days of 30% supplemental oxygen inhibits IH and SCMp after creation of an AVF. These data suggest a role for the short-term administration of low-dose O2 to prevent both IH and SMCp after creation of an AVF that may prolong patency and function. Our study demonstrates that intimal hyperplasia (IH) at the site of an arteriovenous fistula (AVF), as well as IH in the artery proximal to the AVF and IH in the vein distal to the AVF, can be inhibited by the short-term administration of 30% supplemental oxygen. Given the large numbers of end-stage renal disease patients who undergo AVF placement and the high failure of AVFs secondary to IH, this study has widespread implications for the treatment of patients undergoing all forms of arterial and venous interventions and should be translated to the human condition.