Submitted on November 2, 2004
Accepted on January 10, 2005
Alterations in wall shear stress predict sites of neointimal hyperplasia after stent implantation in rabbit iliac arteries
John F LaDisa, Jr.1*, Lars E Olson2, Robert C Molthen3, Douglas A Hettrick4, Phillip F Pratt5, Michael D Hardel6, Judy R Kersten7, David C Warltier8, and Paul S Pagel4
1 Pediatric Cardiology, Stanford University, Stanford, California, USA; Biomedical Engineering, Marquette University, Milwaukee, Wisconsin, USA; Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
2 Biomedical Engineering, Marquette University, Milwaukee, Wisconsin, USA
3 Biomedical Engineering, Marquette University, Milwaukee, Wisconsin, USA; Pulmonary and Critical Care Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
4 Biomedical Engineering, Marquette University, Milwaukee, Wisconsin, USA; Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
5 Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
6 Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
7 Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA; Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
8 Biomedical Engineering, Marquette University, Milwaukee, Wisconsin, USA; Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA; Medicine (Division of Cardiovascular Diseaes), Medical College of Wisconsin, Milwaukee, Wisconsin, USA
* To whom correspondence should be addressed. E-mail: jladisa{at}stanford.edu.
Restenosis resulting from neointimal hyperplasia (NH) limits the effectiveness of intravascular stents. Rates of restenosis vary with stent geometry, but whether stents affect spatial and temporal distributions of wall shear stress (WSS) in vivo is unknown. We tested the hypothesis that alterations in spatial WSS after stent implantation predict sites of NH in rabbit iliac arteries. Antegrade iliac artery stent implantation was performed under angiography, and blood flow was measured before casting 14 or 21 days after implantation. Iliac artery blood flow domains were obtained from 3D microfocal x-ray computed tomography imaging and reconstruction of the arterial casts. Indices of WSS were determined using 3D computational fluid dynamics. Vascular histology was unchanged proximal and distal to the stent. Time-dependent NH was localized within the stented region, and was greatest in regions exposed to low WSS and acute elevations in spatial WSS gradients. The lowest values of WSS spatially localized to the stented area of a theoretical artery progressively increased after 14 and 21 days as NH occurred within these regions. This NH abolished spatial disparity in distributions of WSS. The results suggest that stents may introduce spatial alterations in WSS that modulate NH in vivo.
