Mis-sizing of stent promotes intimal hyperplasia: impact of endothelial shear and intramural stress.

Stent can cause flow disturbances on the endothelium and compliance mismatch and increased stress on the vessel wall. These effects can cause low wall shear stress (WSS), high wall shear stress gradient (WSSG), oscillatory shear index (OSI), and circumferential wall stress (CWS), which may promote neointimal hyperplasia (IH). The hypothesis is that stent-induced abnormal fluid and solid mechanics contribute to IH. To vary the range of WSS, WSSG, OSI, and CWS, we intentionally mismatched the size of stents to that of the vessel lumen. Stents were implanted in coronary arteries of 10 swine. Intravascular ultrasound (IVUS) was used to size the coronary arteries and stents. After 4 wk of stent implantation, IVUS was performed again to determine the extent of IH. In conjunction, computational models of actual stents, the artery, and non-Newtonian blood were created in a computer simulation to yield the distribution of WSS, WSSG, OSI, and CWS in the stented vessel wall. An inverse relation (R(2) = 0.59, P < 0.005) between WSS and IH was found based on a linear regression analysis. Linear relations between WSSG, OSI, and IH were observed (R(2) = 0.48 and 0.50, respectively, P < 0.005). A linear relation (R(2) = 0.58, P < 0.005) between CWS and IH was also found. More statistically significant linear relations between the ratio of CWS to WSS (CWS/WSS), the products CWS × WSSG and CWS × OSI, and IH were observed (R(2) = 0.67, 0.54, and 0.56, respectively, P < 0.005), suggesting that both fluid and solid mechanics influence the extent of IH. Stents create endothelial flow disturbances and intramural wall stress concentrations, which correlate with the extent of IH formation, and these effects were exaggerated with mismatch of stent/vessel size. These findings reveal the importance of reliable vessel and stent sizing to improve the mechanics on the vessel wall and minimize IH.

[1]  Division on Earth Guide for the Care and Use of Laboratory Animals , 1996 .

[2]  Y. Lanir,et al.  Three-dimensional mechanical properties of porcine coronary arteries: a validated two-layer model. , 2006, American journal of physiology. Heart and circulatory physiology.

[3]  M. S. Williams,et al.  Stent and artery geometry determine intimal thickening independent of arterial injury. , 2000, Circulation.

[4]  J. LaDisa,et al.  Three-Dimensional Computational Fluid Dynamics Modeling of Alterations in Coronary Wall Shear Stress Produced by Stent Implantation , 2003, Annals of Biomedical Engineering.

[5]  K. Sorbie,et al.  Experimental and modeling study of Newtonian and non-Newtonian fluid flow in pore network micromodels. , 2006, Journal of colloid and interface science.

[6]  Deepak L. Bhatt,et al.  Appropriate use of drug-eluting stents: balancing the reduction in restenosis with the concern of late thrombosis , 2008, The Lancet.

[7]  D. Tang,et al.  Pattern formation of vascular smooth muscle cells subject to nonuniform fluid shear stress: role of PDGF-beta receptor and Src. , 2003, American journal of physiology. Heart and circulatory physiology.

[8]  Michael R Moreno,et al.  Effects of stent design parameters on normal artery wall mechanics. , 2006, Journal of biomechanical engineering.

[9]  M. Thubrikar,et al.  Inhibition of Atherosclerosis Associated with Reduction of Arterial Intramural Stress in Rabbits , 1988, Arteriosclerosis.

[10]  G. Schuler,et al.  Influence of residual stenosis after percutaneous coronary intervention with stent implantation on development of restenosis and stent thrombosis. , 2003, The American journal of cardiology.

[11]  S Chien,et al.  Effects of hematocrit and plasma proteins on human blood rheology at low shear rates. , 1966, Journal of applied physiology.

[12]  A. Ionescu,et al.  Bare metal stent restenosis is not a benign clinical entity. , 2006, American heart journal.

[13]  Ghassan S. Kassab,et al.  A Simulation of Vessel–Clamp Interaction: Transient Closure Dynamics , 2009, Annals of Biomedical Engineering.

[14]  P. Prendergast,et al.  Cardiovascular stent design and vessel stresses: a finite element analysis. , 2005, Journal of biomechanics.

[15]  N. S. Vlachos,et al.  Numerical modeling of simulated blood flow in idealized composite arterial coronary grafts: steady state simulations. , 2007, Journal of biomechanics.

[16]  E. Edelman,et al.  Pushing drug-eluting stents into uncharted territory: simpler than you think--more complex than you imagine. , 2006, Circulation.

[17]  A. Obukhov,et al.  Exercise training decreases store-operated Ca2+entry associated with metabolic syndrome and coronary atherosclerosis. , 2010, Cardiovascular research.

[18]  Luoding Zhu,et al.  Effects of stent sizing on endothelial and vessel wall stress: potential mechanisms for in-stent restenosis. , 2009, Journal of applied physiology.

[19]  William Wijns,et al.  A Cause for Concern , 2007 .

[20]  J. Gunn,et al.  Coronary artery stretch versus deep injury in the development of in-stent neointima , 2002, Heart.

[21]  D. A. Mcdonald Blood flow in arteries , 1974 .

[22]  Peter F. Davies,et al.  Shear Stress Biology of the Endothelium , 2005, Annals of Biomedical Engineering.

[23]  E. Edelman,et al.  Systemic Inflammation Induced by Lipopolysaccharide Increases Neointimal Formation After Balloon and Stent Injury in Rabbits , 2002, Circulation.

[24]  S. Chien,et al.  Shear stress induction of the tissue factor gene. , 1997, The Journal of clinical investigation.

[25]  G. Kassab,et al.  Computational Modeling of Coronary Stents , 2010 .

[26]  E. Antman,et al.  Association of a negative residual stenosis following rescue/adjunctive percutaneous coronary intervention with impaired myocardial perfusion and adverse outcomes among ST-segment elevation myocardial infarction patients. , 2005, Journal of the American College of Cardiology.

[27]  Yuan-Cheng Fung,et al.  Introduction to Bioengineering , 2001 .

[28]  D. Ku BLOOD FLOW IN ARTERIES , 1997 .

[29]  Andreas O Frank,et al.  Blood flow in stented arteries: a parametric comparison of strut design patterns in three dimensions. , 2005, Journal of biomechanical engineering.

[30]  Fred J. Clubb,et al.  INCREASED ARTERY WALL STRESS POST-STENTING LEADS TO GREATER INTIMAL THICKENING , 2010, Laboratory Investigation.

[31]  James E. Moore,et al.  Stented artery biomechanics and device design optimization , 2007, Medical & Biological Engineering & Computing.

[32]  T. Moriya,et al.  Inflammatory markers and restenosis in peripheral percutaneous angioplasty with intravascular stenting: current concepts. , 2011, Annals of vascular surgery.

[33]  Yi Liu,et al.  Fluid–Structure Interaction (FSI) Modeling in the Cardiovascular System , 2010 .

[34]  R. Virmani,et al.  Vascular response to coronary artery stenting in mature and juvenile swine. , 2011, Cardiovascular revascularization medicine : including molecular interventions.

[35]  Peter Jüni,et al.  Correlation of Intravascular Ultrasound Findings With Histopathological Analysis of Thrombus Aspirates in Patients With Very Late Drug-Eluting Stent Thrombosis , 2009, Circulation.

[36]  C Kleinstreuer,et al.  Effect of carotid artery geometry on the magnitude and distribution of wall shear stress gradients. , 1996, Journal of vascular surgery.

[37]  E. Edelman,et al.  Leukocyte recruitment and expression of chemokines following different forms of vascular injury , 2003, Vascular medicine.

[38]  A. Kastrati,et al.  Intracoronary Stenting and Angiographic Results: Strut Thickness Effect on Restenosis Outcome (ISAR-STEREO) Trial , 2001, Circulation.

[39]  G. Dangas,et al.  Drug-eluting stents in the real world: how intravascular ultrasound can improve clinical outcome. , 2008, The American journal of cardiology.

[40]  Thomas Wischgoll,et al.  Flow patterns in three-dimensional porcine epicardial coronary arterial tree. , 2007, American journal of physiology. Heart and circulatory physiology.

[41]  A. Kastrati,et al.  [Intracoronary Stenting and Angiographic Results Strut Thickness Effect on Restenosis Outcome (ISAR-STEREO) Trial]. , 2012, Vestnik rentgenologii i radiologii.

[42]  Deepak L. Bhatt,et al.  The Problem of Persistent Platelet Activation in Acute Coronary Syndromes and Following Percutaneous Coronary Intervention , 2008, Clinical cardiology.

[43]  S. Chien Mechanotransduction and endothelial cell homeostasis: the wisdom of the cell. , 2007, American journal of physiology. Heart and circulatory physiology.

[44]  C. Gans,et al.  Biomechanics: Motion, Flow, Stress, and Growth , 1990 .

[45]  Anthony A Bavry,et al.  Late thrombosis of drug-eluting stents: a meta-analysis of randomized clinical trials. , 2006, The American journal of medicine.

[46]  Joel L. Berry,et al.  Experimental and Computational Flow Evaluation of Coronary Stents , 2000, Annals of Biomedical Engineering.

[47]  William Wijns,et al.  Stent thrombosis late after implantation of first-generation drug-eluting stents: a cause for concern. , 2007, Circulation.

[48]  H. Bergmeister,et al.  Biocompatibility and performance of the Wallstent and several covered stents in a sheep iliac artery model. , 2001, Journal of vascular and interventional radiology : JVIR.