title: Boundary layer infusion of nitric oxide reduces early smooth muscle cell proliferation in the endarterectomized canine artery.
abstract: To evaluate the direct effect of nitric oxide (NO) on vascular smooth muscle cell (SMC) proliferation in vivo, we used an expanded polytetrafluoroethylene (ePTFE)-based local infusion device to deliver an NO donor, proline/NO (PROLI/NO), to the luminal boundary layer of endarterectomized artery and the distal anastomosis of the graft in a canine model. Once delivered to the blood, PROLI/NO releases NO by a mechanism involving pH-dependent decomposition. Six dogs underwent bilateral femoral artery endarterectomies. ePTFE infusion devices, blindly primed with PROLI/NO to one artery or proline to the contralateral vessel, were anastomosed proximal to the injured segments so that each animal served as its own control. PROLI/NO or proline was continuously delivered for 7 days from an osmotic reservoir, through the wall of the graft infusion device. Euthanasia was carried out at 7 days, and the processed specimens were blindly analyzed for SMC proliferation at both graft anastomoses and endarterectomized segments by a bromodeoxyuridine index assay. All dogs survived with no clinical side effects. In comparing the treated and control vessels, NO released from PROLI/NO significantly reduced SMC proliferation by 43% (13.24 +/- 1.24% versus 23.24 +/- 1.01%, P = 0.004) at the distal anastomoses and by 68% (10.58 +/- 1.63% versus 25.17 +/- 3.39%, P = 0.007) at endarterectomized segments. However, there was no significant difference in blood flow measurements between treated and control arteries (56.25 +/- 6.50 ml/min versus 46.50 +/- 3.20 ml/min, P = 0.094). These data demonstrate that local boundary layer infusion of NO released from PROLI/NO significantly reduces SMC proliferation in injured arteries with no effect on regional blood flow. This study suggests a new strategy to inhibit early SMC proliferation in injured arteries and probably to control intimal hyperplastic lesion formation in the manipulated vessels.
authors.affiliation: Department of Surgery, Veterans Affairs Medical Center, Decatur, Georgia 30033, USA.
authors.forename: C
authors.initials: C
authors.lastname: Chen
authors.forename: S R
authors.initials: SR
authors.lastname: Hanson
authors.forename: L K
authors.initials: LK
authors.lastname: Keefer
authors.forename: J E
authors.initials: JE
authors.lastname: Saavedra
authors.forename: K M
authors.initials: KM
authors.lastname: Davies
authors.forename: T C
authors.initials: TC
authors.lastname: Hutsell
authors.forename: J D
authors.initials: JD
authors.lastname: Hughes
authors.forename: D N
authors.initials: DN
authors.lastname: Ku
authors.forename: A B
authors.initials: AB
authors.lastname: Lumsden
mesh_terms: D000714:Anastomosis, Surgical; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004285:Dogs; D004691:Endarterectomy / Q000295:instrumentation / Q000379:methods*; D005263:Femoral Artery / Q000473:pathology / Q000601:surgery; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology*; D009569:Nitric Oxide / Q000494:pharmacology*; D011138:Polytetrafluoroethylene
chemical_list: D009569:Nitric Oxide; D011138:Polytetrafluoroethylene