Local delivery of nitric oxide from an eluting stent to inhibit neointimal thickening in a porcine coronary injury model.
To assess the effect of a NO-eluting stent on reducing neointimal thickening in a porcine coronary artery stent injury model, sodium nitroprusside (SNP), a NO donor, was incorporated into polyurethane (PU) polymer and coated onto metallic coil stents, and two types of stents with thin and thick barrier coatings were characterized. In vivo biological activity of the NO-eluting stents was assessed by measurement of coronary arterial cGMP levels in 32 pigs/64 arteries at days 1, 2, 7 and 14. Morphometric analyses were performed in 16 pigs to determine the effect of NO-eluting stents on neointimal hyperplasia 28 days following arterial injury. The SNP-coated stents released NO in a controlled manner for up to 4 weeks in the in vitro experiments and an increase in local tissue cGMP levels was demonstrated for up to 14 days. The neointimal area at 28 days was not diminished, however, by NO eluded from either stents of thin or thick barriers (control bare stent - 0.66 mm2, control PU stent - 0.68 mm2, SNP-PU thin coating stent - 0.78 mm2, SNP-PU thick coating stent - 0.85 mm2; all p=NS). In conclusion, the SNP-coated polymer stent exerted a local biological effect on the arterial wall, with sustained elevation of cGMP level. Although local delivery of NO from this device did not reduce neointimal hyperplasia in this porcine model, this polymer-coated stent might be a promising tool for administration of other agents that may modify the reparative tissue responses leading to restenosis.
Yoon
Jung Han
JH
Department of Cardiology, F25, The Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195-5066, USA.
Wu
Chiung Jen
CJ
Homme
James
J
Tuch
Ronald J
RJ
Wolff
Rodney G
RG
Topol
Eric J
EJ
Lincoff
A Michael
AM
D000818:Animals; D020099:Coated Materials, Biocompatible; D003331:Coronary Vessels / Q000293:injuries*; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000494:pharmacology; D015607:Stents; D013552:Swine; D017539:Tunica Intima / Q000187:drug effects*; D014947:Wounds and Injuries / Q000473:pathology*
D020099:Coated Materials, Biocompatible; D009569:Nitric Oxide