Segmental vessel wall shear stress and neointimal formation after sirolimus-eluting stent implantation: physiological insights in a porcine coronary model.
BACKGROUND
Low vessel-wall shear stress promotes atherosclerosis and restenosis. We conducted serial analysis of vessel-wall shear stress following placement of metal and sirolimus (SRL) stents to determine the relationship between shear stress and neointima.


METHODS
Serial quantitative coronary angiography, intracoronary ultrasound (IVUS), and Doppler flow analysis were performed at baseline, immediately poststent, and at 30 and 90 days on 16 stents (metal, n = 8; SRL, n = 8) implanted in the coronary arteries of eight miniswine. Segmental vessel-wall shear stress (dyn/cm2) was calculated at 10 sections within the stent and normalized to the average proximal and distal reference vessel shear stress using IVUS and hyperemic average peak flow velocity. At 90 days, histological analysis was completed to determine vessel-wall morphometry on corresponding sections from each stent.


RESULTS
Stent placement resulted in a similar degree of in-stent stenosis (-5% to 25%) and immediate post-in-stent shear stress. At 30 days, the IVUS neointimal cross-sectional area and percentage of area stenosis were significantly less in SRL (1.2+/-0.8 mm2; 12.7+/-8.5%) versus metal stents (2.3+/-0.4 mm2; 28.2+/-3.4%, P < .003). In-stent normalized shear stress was less for SRL (0.93+/-0.07) versus metal (1.07+/-0.08, P = .002) stents. At 90 days, the mean neointimal area was similar for the SRL (2.50+/-0.47 mm2) and metal stents (2.72+/-1.15 mm2). Linear regression documented a negative correlation between poststent shear stress and neointima for metal stents (r = .61, P < .0001). In the SRL stents, however, the post-in-stent shear stress had a positive correlation with neointima (r = .40, P = .0002).


CONCLUSIONS
The placement of oversized stents causes alteration of segmental vessel-wall shear stress, which appears to be an important physiological stimulus for neointimal formation, and may influence the pharmacodynamics of SRL-eluting stent in the porcine coronary model.
Carter
Andrew J
AJ
Medical Device Research Laboratory, Borgess Medical Center, Kalamazoo, MI 49024, USA. andrewcarter@borgess.com
Wei
Wei
W
Gibson
Lori
L
Collingwood
Robin
R
Tio
Fermin
F
Dooley
John
J
Kopia
Gregory A
GA
D000704:Analysis of Variance; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D001783:Blood Flow Velocity / Q000502:physiology; D019917:Blood Vessel Prosthesis Implantation / Q000379:methods*; D017023:Coronary Angiography / Q000379:methods; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000601:surgery*; D016503:Drug Delivery Systems / Q000295:instrumentation*; D023421:Models, Animal; D020123:Sirolimus / Q000627:therapeutic use*; D015607:Stents; D013314:Stress, Mechanical; D013552:Swine; D013556:Swine, Miniature; D013997:Time Factors; D017539:Tunica Intima / Q000187:drug effects* / Q000503:physiopathology; D018084:Ultrasonography, Interventional / Q000379:methods
D000903:Antibiotics, Antineoplastic; D020123:Sirolimus