Effects of diffusion coefficients and struts apposition using numerical simulations for drug eluting coronary stents.

In the context of drug eluting stent, we present two-dimensional numerical models of mass transport of the drug in the wall and in the lumen to study the effect of the drug diffusion coefficients in the three principal media (blood, vascular wall, and polymer coating treated as a three-compartment problem) and the impact of different strut apposition configurations (fully embedded, half embedded, and not embedded). The different conditions were analyzed in terms of their consequence on the drug concentration distribution in the arterial wall. We apply the concept of the therapeutic window to the targeted vascular wall region and derive simple metrics to assess the efficiency of the various stent configurations. Although most of the drug is dispersed in the lumen, variations in the blood flow rate within the physiological range of coronary blood flow and the diffusivity of the drug molecule in the blood were shown to have a negligible effect on the amount of drug in the wall. Our results reveal that the amount of drug cumulated in the wall depends essentially on the relative values of the diffusion coefficients in the polymer coating and in the wall. Concerning the strut apposition, it is shown that the fully embedded strut configuration would provide a better concentration distribution.

[1]  F. Boey,et al.  In vitro study of release mechanisms of paclitaxel and rapamycin from drug-incorporated biodegradable stent matrices. , 2004, Journal of controlled release : official journal of the Controlled Release Society.

[2]  E. Edelman,et al.  Specific binding to intracellular proteins determines arterial transport properties for rapamycin and paclitaxel. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[3]  Kambiz Vafai,et al.  Modeling of low-density lipoprotein (LDL) transport in the artery—effects of hypertension , 2006 .

[4]  A. Furber,et al.  Coronary Blood Flow Assessment After Successful Angioplasty for Acute Myocardial Infarction Predicts the Risk of Long-Term Cardiac Events , 2004, Circulation.

[5]  Frank Litvack,et al.  Local Drug Delivery via a Coronary Stent With Programmable Release Pharmacokinetics , 2003, Circulation.

[6]  Abdul I. Barakat,et al.  Computational Study of Fluid Mechanical Disturbance Induced by Endovascular Stents , 2005, Annals of Biomedical Engineering.

[7]  Gerhard Rappitsch,et al.  Numerical modelling of shear-dependent mass transfer in large arteries , 1997 .

[8]  B. Massie,et al.  Heart failure: how big is the problem? Who are the patients? What does the future hold? , 2003, American heart journal.

[9]  E. Edelman,et al.  Impact of transport and drug properties on the local pharmacology of drug-eluting stents , 2003, International journal of cardiovascular interventions.

[10]  R. Lutz,et al.  Simulated Lipoprotein Transport in the Wall of Branched Arteries , 2000, ASAIO journal.

[11]  J. Gunn,et al.  Stent coatings and local drug delivery; state of the art. , 1999, European heart journal.

[12]  E. Edelman,et al.  Carrier proteins determine local pharmacokinetics and arterial distribution of paclitaxel. , 2001, Journal of pharmaceutical sciences.

[13]  M. Helmus,et al.  Physical characterization of controlled release of paclitaxel from the TAXUS Express2 drug-eluting stent. , 2004, Journal of biomedical materials research. Part A.

[14]  E. Edelman,et al.  Local drug delivery: an emerging approach in the treatment of restenosis , 2000, Vascular medicine.

[15]  R E Vlietstra,et al.  Restenosis and the proportional neointimal response to coronary artery injury: results in a porcine model. , 1992, Journal of the American College of Cardiology.

[16]  E. Edelman,et al.  Arterial paclitaxel distribution and deposition. , 2000, Circulation research.

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

[18]  W. Wijns Incidence of stent under-deployment as a cause of in-stent restenosis in long stents Take your lesson ! , 2004, The International Journal of Cardiovascular Imaging.

[19]  P. Gurbel,et al.  Platelet activation after stenting with heparin-coated versus noncoated stents. , 2003, American heart journal.

[20]  E. Edelman,et al.  Coated stents: local pharmacology. , 1998, Seminars in interventional cardiology : SIIC.

[21]  Campbell D K Rodgers Drug-eluting stents: role of stent design, delivery vehicle, and drug selection. , 2002, Reviews in cardiovascular medicine.

[22]  Joel L. Berry,et al.  Fluid and Solid Mechanical Implications of Vascular Stenting , 2002, Annals of Biomedical Engineering.

[23]  E. Edelman,et al.  Physiological Transport Forces Govern Drug Distribution for Stent-Based Delivery , 2001, Circulation.

[24]  R. Mongrain,et al.  Study of catheter designs and drug mixing processes using 2D steady numerical simulations , 2006, Medical & Biological Engineering & Computing.

[25]  J. Reddy,et al.  The Finite Element Method in Heat Transfer and Fluid Dynamics , 1994 .

[26]  E. Edelman,et al.  Computational simulations of local vascular heparin deposition and distribution. , 1996, The American journal of physiology.

[27]  P. Paiement,et al.  Swine model of coronary restenosis: effect of a second injury. , 1996, Catheterization and cardiovascular diagnosis.

[28]  B. A. French,et al.  Use of nitric‐oxide‐eluting polymer‐coated coronary stents for prevention of restenosis in pigs , 2000, Coronary artery disease.

[29]  I. Barasoain,et al.  Fast Kinetics of Taxol Binding to Microtubules , 2003, The Journal of Biological Chemistry.

[30]  J. Tardif,et al.  Incidence of Stent Under-Deployment as a Cause of in-Stent Restenosis in Long Stents , 2004, The International Journal of Cardiovascular Imaging.

[31]  J. Hubbard,et al.  Physical characterization of heparin by light scattering. , 1995, Journal of pharmaceutical sciences.

[32]  Rossella Fattori,et al.  Drug-eluting stents in vascular intervention , 2003, The Lancet.

[33]  P. Henson,et al.  The dosimetry for a coronary artery stent coated with radioactive 188Re and 32P , 2000, Physics in medicine and biology.

[34]  Shigeru Tada,et al.  Internal elastic lamina affects the distribution of macromolecules in the arterial wall: a computational study. , 2004, American journal of physiology. Heart and circulatory physiology.

[35]  Patrick W. Serruys,et al.  Handbook of Coronary Stents , 1997 .

[36]  S. Ellis,et al.  Arterial injury and the enigma of coronary restenosis. , 1992, Journal of the American College of Cardiology.

[37]  Walter Welkowitz,et al.  Engineering hemodynamics: Application to cardiac assist devices , 1977 .

[38]  Andreas O Frank,et al.  Computational fluid dynamics and stent design. , 2002, Artificial organs.

[39]  P. Teirstein,et al.  Restenosis after angioplasty , 2001, Current treatment options in cardiovascular medicine.

[40]  A. Tzafriri,et al.  Strut Position, Blood Flow, and Drug Deposition: Implications for Single and Overlapping Drug-Eluting Stents , 2005, Circulation.

[41]  N. Krott,et al.  Long-term assessment of a novel biodegradable paclitaxel-eluting coronary polylactide stent. , 2004, European heart journal.

[42]  L. Kalachev,et al.  Numerical Simulation of Local Pharmacokinetics of a Drug after Intravascular Delivery with an Eluting Stent , 2002, Journal of drug targeting.