Flow Responsive Remodelling after Angioplasty is Dependent on Oxidant
Stress M R Ward*, P S Tsao, N A Herity, J P
Cooke, A C Yeung. Stanford University, Stanford, California, USA. Remodeling is a major
cause of restenosis after angioplasty. The mechanisms are unclear but may involve oxidant stress due to injury
and altered flow. We performed balloon overstretch injury to the right common
carotid of 30 rabbits followed by ligation of the right external carotid (low
flow LO) or left common carotid (high flow, HI). 5 HI and 5 LO animals were
maintained on each of normal diet (N), 1% cholesterol diet to create oxidant
stress (C) or C + the antioxidant PDTC (22±4mg/kg) (A). Morphometry of perfusion fixed
vessels at 4 weeks, normalized for EEL area of uninjured control (table),
showed that flow-dependent remodeling
after angioplasty was bidirectionally enhanced in C compared with N.
Angiography showed similar changes. Mean doppler flow velocities
(initial/post-ligation/follow-up, cm/sec) had almost normalised in N (HI
30/49/35, LO 32/9/26) but had overcompensated in C (HI 32/49/22, LO 30/11/25).
Remodeling was markedly attenuated by concommitant antioxidant therapy and flow
had only partially normalised (HI 26/42/34, LO 27/7/16). Mean Vessel Area of A
LO and A HI were significantly larger than uninjured controls suggesting that
antioxidants may also affect flow-independent remodeling. We conclude that
hypercholesterolemia enhances and antioxidants attenuate flow-dependent
remodeling after angioplasty and that antioxidants may also attenuate
flow-independent remodeling. AREA N
HI* N
LO C
HI*† C
LO† A
HI‡ A
LO†‡ LUMEN 0.75±0.09 0.53±0.05 1.16±0.07 0.39±0.05 0.85±0.08 0.75±0.06 INTIMA 0.04±0.01 0.05±0.02 0.04±0.02 0.06±0.02 0.06±0.01 0.10±0.04 EEL 1.10±0.14 0.78±0.02 1.48±0.08 0.61±0.03 1.19±0.10 1.09±0.06 For Lumen and EEL Area * P
< 0.05 vs LO, † P < 0.05 vs N, ‡P < 0.05 vs C.
