title: Low flow promotes instent intimal hyperplasia. Comparison with lumen loss in balloon-injured and uninjured vessels and the effects of the antioxidant pyrrolidine dithiocarbamate.
abstract: Low flow (LF) promotes late lumen loss after angioplasty by exacerbating inward remodelling through redox-sensitive mechanisms. Stents eliminate inward remodelling and the effect of LF on in-stent restenosis is uncertain. We performed over-sized (1.3-1.5:1) stenting (S) and balloon injury (in the same vessel, B) to the carotid arteries of cholesterol-fed rabbits and compared 28-day late lumen loss with that in an uninjured segment in the same vessel (U). Vessels (n = 5 animals per group) were subjected to high (H), normal (N) and low (L) flow in animals fed either vehicle (V) or the antioxidant pyrrolidine dithiocarbamate, PDTC (P). LF significantly increased in-stent neointima formation relative to normal and high flow (SLV 0.72 +/- 0.07 mm(2) versus SNV 0.43 +/- 0.08 mm(2) versus SHV 0.28 +/- 0.04 mm(2), P < 0.05). However, LF resulted in greater lumen loss in segments from the same vessel subject to balloon injury (lumen SLV 5.18 +/- 0.40 mm(2) and SNV 5.32 +/- 0.40 mm(2) versus BLV 1.28 +/- 0.33 mm(2) and BNV 2.19 +/- 0.28 mm(2)), by greater enhancement of inward remodelling. In addition, inward remodelling and lumen loss due to LF were greater in balloon-injured segments than in adjacent uninjured segments where shear homeostatic remodelling occurs (lumen BLV 1.28 +/- 0.33 mm(2) versus ULV 1.52 +/- 0.22 mm(2)). Lastly, while PDTC effectively reduced intima formation and inward remodelling due to LF in balloon-injured vessels there was no effect on flow-dependent neointima formation in stented vessels. We conclude that LF accentuates in-stent neointima formation, but that flow-dependent lumen loss after stenting is less than that after balloon injury. When LF is present lumen loss can be minimised by antioxidants or stenting.
authors.affiliation: Vascular Biology Laboratory, Cardiology Department, Royal North Shore Hospital, Sydney, Australia.
authors.forename: Colm G
authors.initials: CG
authors.lastname: Hanratty
authors.forename: Melanie
authors.initials: M
authors.lastname: Murrell
authors.forename: Levon M
authors.initials: LM
authors.lastname: Khachigian
authors.forename: Philip S
authors.initials: PS
authors.lastname: Tsao
authors.forename: Michael R
authors.initials: MR
authors.lastname: Ward
mesh_terms: D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001783:Blood Flow Velocity; D006965:Hyperplasia; D011759:Pyrrolidines / Q000494:pharmacology*; D011817:Rabbits; D015607:Stents / Q000009:adverse effects; D013859:Thiocarbamates / Q000494:pharmacology*; D017539:Tunica Intima / Q000473:pathology*
chemical_list: D000975:Antioxidants; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid