Flow-responsive remodeling after angioplasty is enhanced by high cholesterol diet. Prevention with pyrrolidine dithiocarbamate.
We examined the effects of high cholesterol diet and pyrrolidine dithiocarbamate (PDTC) on flow-dependent remodeling after angioplasty. After right common carotid balloon-injury, the right external carotid (low flow) or left common carotid artery were ligated (high flow) in rabbits fed normal diet, 1% cholesterol diet without or with the antioxidant PDTC for 7 days pre- and 7-28 days post-injury. Angiographic lumen diameter was significantly greater at 28 days in high flow than low flow normal diet animals, attributable on perfusion-fixed vessel morphometry to altered remodeling (area within the external elastic lamina: high flow 1.85+/-0.24 vs. low flow 1.31+/-0.04 mm(2), P<0.05) rather than differences in neointima formation or vessel tone. In animals on 1% cholesterol diet high flow remodeling was significantly enhanced (area within the external elastic lamina 3.13+/-0.17 mm(2), P<0.05 vs. high flow normal diet) but low flow inward remodeling was similar (area within the external elastic lamina 1.29+/-0.07 mm(2)). Mean Doppler flow velocities (initial/post-ligation/28 day follow-up, cm/s) had almost normalized in normal diet animals (high flow 30/49/35, low flow 32/9/26) but showed overcompensation in 1% cholesterol diet animals (high flow 32/49/22, low flow 30/11/25). PDTC therapy markedly attenuated remodeling (area within the external elastic lamina: high flow 2.20+/-0.18, and low flow 2.00+/-0.11 both P<0.05 vs. 1% cholesterol diet alone) and flow velocities only partially normalized (high flow 26/42/34, low flow 27/7/16). We conclude that hypercholesterolemia enhances and PDTC attenuates flow-dependent remodeling after angioplasty.
Ward
Michael R
MR
Division of Cardiovascular Medicine, Stanford University, Stanford, CA, USA. mrward@doh.health.nsw.gov.au
Tsao
Philip S
PS
Herity
Niall A
NA
Cooke
John P
JP
Yeung
Alan C
AC
D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001783:Blood Flow Velocity; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology*; D020212:Carotid Artery Injuries / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology; D002404:Catheterization / Q000009:adverse effects; D002533:Cerebral Angiography; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D011759:Pyrrolidines / Q000494:pharmacology*; D011817:Rabbits; D013859:Thiocarbamates / Q000494:pharmacology*; D014463:Ultrasonography
D000975:Antioxidants; D002791:Cholesterol, Dietary; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid