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By Neil Bulman-Fleming, Rosaire Mongrain, and Isam Faik, McGill University, Montréal, Canada;
and Olivier Bertrand, Université Laval, Québec City, Canada
View the pdf of this Supplement
Minimally invasive catheter-based interventions
have revolutionized the world of heart surgery.
Lengthy recovery times associated with
open-heart surgeries are routinely avoided through
the use of balloon angioplasty and coronary stenting.
Stenting is a process involving the deployment of a
metal scaffolding inside a blocked artery to maintain
blood flow to the heart muscle. Though these techniques
have achieved a high degree of success, they
are not by any means perfect. In a large percentage
of cases, the patient’s body responds to the implantation
of a stent by growing many layers of smooth
muscle cells over the implant. This response can often
lead to blockage of the coronary artery – the exact
problem that the stent is intended to solve initially.
One example of the quarter-domain stent
geometries used in the numerical model
(a) Longitudinal (constant q) and (b) cylindrical (constant radius) sections of the therapeutic region
after 7 days; the flow travels from bottom to top in (a), and the thickness of the vessel wall is
exaggerated to illustrate the spread of the drug
One promising solution to this problem is the deployment
of drug-loaded stents in diseased arteries. By coating
the stent structure with a chemical-infused
polymer, drugs that limit smooth muscle cell growth
can be delivered directly to the area responsible.
Over a critical therapeutic period of about one month,
uniform drug distribution can effectively eliminate
the proliferation of smooth muscle cells. The challenge
is to achieve a uniform drug distribution in the region
of the stent, and to verify that an appropriate dose is
provided.
Animal trials investigating drug-loaded stents can
give a general indication of an implant’s success, but
do not provide accurate dose distributions in the
arterial tissue. One practical, inexpensive and efficient
means of studying these dose distributions is through
numerical modeling. Although real tissues are complex,
irregular, and widely varied among patients, appropriate
simplifications to the coronary artery tissues can
yield meaningful general dose distribution results.
In a study carried out at McGill University in Montréal,
Canada, FIDAP was used to model the pharmacokinetics
of drug-eluting stents. The goal of the study was
to develop a tool for evaluating the dose delivery characteristics
of real 3D stent geometries. Such a tool could
then be used by stent designers to modify geometries
in order to ensure optimal dose delivery outcomes.
Three common stent geometries were modeled,
and a simulation was carried out in a quarter-artery
domain. By examining mass concentration over time
at field points throughout the arterial wall, an estimate
for how the drug moves through the solution domain
was obtained. Dose homogeneity, final concentration,
and stent contact area values were combined into a
single parameter, the “Local Delivery Effectiveness
Score” (LDES). This score, out of ten, combines key
factors that may contribute to the success of particular
stent designs, and provides a simple, one-step
evaluation criterion.
In order to increase the accuracy and realism
of this basic model, work is now underway
to use actual patient-specific artery
geometries in a numerical model. Images
obtained using Intravascular Ultrasound (IVUS)
can be reconstructed from individual transverse
“slices” to build a 3D model. Such models
incorporate arterial tissues as well as calcified
deposits and other inclusions known to be
present in diseased coronary arteries. These
geometries, along with accurate diffusion information
for the tissues represented in them,
could serve as the basis for FIDAP simulations
which would allow the optimization of stent
and drug loading parameters tailored to each
patient’s specific needs.
References:
N. Bulman-Fleming, R. Mongrain, and
O.F. Bertrand, 3D Numerical Simulations of Stent
Based Local Drug Delivery Using Realistic Post
Implantation Geometries, Endocoronary
Biomechanics and Restenosis Symposium,
Paris, 2003.
R. Mongrain, N. Bulman-Fleming, J.C. Tardif,
S. Plante, and O.F. Bertrand, Numerical
Simulations of Local Pharmacokinetics of a Drug
Delivered from an Eluting Stent, in Advanced
Materials for Biomedical Applications, edited by
D. Mantovani, Canadian Institute of Mining,
Metallurgy and Petroleum, ISBN
1-894475-25-9, 399, pp.213-223, 2002.
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