Coronary artery disease is the most common type of heart diseases and the leading cause of death worldwide due to heart disease. It occurs when the arteries that supply blood to the heart become narrowed or blocked by a buildup of cholesterol and other material at the inner wall of the artery. Limitation of blood flow to the heart causes ischemia of the myocardial cells. Myocardial cells may die from lack of oxygen and this is called a myocardial infarction - or more commonly: a heart attack.
Treatment options include medication, surgery or catheter-based procedures. Several types of catheter-based procedures are available. During balloon angioplasty, a special balloon catheter is passed into the narrowed segment of the artery and expands the balloon, which thus opens the artery and compresses the blockage against the wall of the artery. Stents are very small metal mesh-tubes that can be inserted via a balloon catheter into the narrowed segment of the artery. When the balloon is inflated, the stent expands and is embedded into the artery vessel wall, which thus opens the previously narrowed segment of artery. The balloon is then deflated and removed along with the catheter, and the stent is left behind to serve as a metal framework for the artery. In case of drug eluting stents a certain amount of anti-flammating drug is loaded in the coating over the base stent. This drug is released at the wall of diseased artery so that restenosis cannot take place at the place of artery where the stent has been implanted.
In this thesis a drug eluting stent was studied where there was a biodegradable coating over a bare metal stent in which there was some amount of therapeutic drug. The degradation of the biodegradable coating layer thickness was determined with respect to time which was actually representing the remaining drug concentration in the coating layer. Then using this variable drug concentration as the drug concentration at initial tissue layer concentration profile of drug in tissue layer with respect to time and position was determined using finite volume algorithm, where this algorithm was coded using MATLAB programming language.
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Md. Iqbal Hossain
Md. Iqbal Hossain obtained a Ph.D. from the School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore, and has been serving as an Assistant Professor at the Department of Chemical Engineering, Bangladesh University of Engineering and Technology. He is also a Senior Member of the American Institute of Chemical Engineers. His areas of expertise are multiphase flow, hydrodynamics and measurement-computational techniques.
Nadia Sultana obtained her B.Sc. and M.Sc. from the Department of Chemical Engineering, Bangladesh University of Engineering and Technology. She obtained her second M.Sc. from the Department of Chemical Engineering, Texas Tech University. She is currently a Ph.D. Candidate at Texas Tech University. In her first M.Sc. degree, her research focused on the simulation of a 2D mass transfer profile in a CAD drug eluting stent. In her second M.Sc. degree, she worked with a 3D alginate gel micro-bead (LbL surface modified) based microenvironment for 3T3-L1 cell cultures. Currently, she is researching on the process of heterogeneous crystal nucleation for the energetic material 2, 4, 6-trinitrotoluene (TNT).
- Simulation of Mass Transfer Phenomenon in a CAD Drug Eluting Stent System
- AUTHOR'S ACKNOWLEDGMENTS
- Chapter One INTRODUCTION
- 1.1 Background of the Study
- 1.2 Objective of the study
- 1.3 Scope of the Study
- 1.4 Thesis Organization
- Chapter Two LITERATURE REVIEW
- 2.1 Background of Current DES Technology
- 2.2 Current State of the Art: DES
- 2.2.1 First Generation DES
- 2.2.2 Second Generation DES
- 2.2.3 Bioresorbable Polymer Stents
- 2.3 Long-term DES Safety
- 2.4 Other uses of Stents
- 2.4.1 Stents in Urology
- 2.4.2 Stents for Managements of Tracheobronchial Obstruction
- 2.4.3 Stents in the Esophagus and Gastrointestinal Tract
- 2.5 Theoretical Models to Describe Drug Releasing Behavior
- 2.6 Conclusion
- Chapter Three OBJECTTIVE WITH SPECIFIC AIMS AND RESEARCH SIGNIFICANCE
- 3.1 Objectives of Study with Specific Aims
- 3.2 Research Significance
- Chapter Four RESEARCH METHODOLOGY
- 4.1 Governing Equation of the Problem
- 4.1.1 Dimensionless Parameter of Drug Release
- 4.1.2 Diffusion in Porous Material
- 4.1.3 Artery Wall Classification
- 4.2 Computational Fluid Dynamics
- 4.2.1 Finite Volume Method
- 4.3 Simulation of the Governing Equation
- 4.3.1 Solution of 1D Unsteady Concentration Equation
- 4.3.2 Solution of 2D Unsteady Concentration Equation
- 4.3.3 Solution of Concentration Equation of BSMT
- 4.3.4 Solution of Equation Describing Coating Thickness
- Chapter Five RESULTS AND DISCUSSION
- 5.1 Solution of the Coating Thickness Equation
- 5.2 Solution of Unsteady 1D Concentration Governing Equation
- 5.2.1 Drug Concentration with respect to Radial Position
- 5.2.2 Drug Concentration with respect to Time
- 5.3 Solution of Unsteady 2D Concentration Governing Equation
- 5.3.1 Drug Concentration Variation at Time-Radius Plane
- 5.3.2 Drug Concentration Variation at r - z Plane
- 5.3.3 Drug Concentration Variation at time - z Plane
- 5.4 Grid Independency Test for the Models
- 5.4.1 Grid Independency Test for 1D Concentration Model
- 5.4.2 Grid Independency Test for 2D Concentration Model
- Chapter Six CONCLUSION
- 6.1 Conclusions
- 6.2 Recommendations for Future Work
- Appendix A SOME NECESSARY THEORIES OF FINITE VOLUME METHOD
OBJECTIVE WITH SPECIFIC AIMS AND RESEARCH SIGNIFICANCE:
3.1 Objectives of Study with Specific Aims:
Coronary artery disease is the most common type of heart diseases and the leading cause of death worldwide due to heart disease. The drug-eluting stents is generally considered as the best catheter-based therapy for coronary artery disease. However, the mass transfer of the drug from DES to the tissue is not fully understood till date. Hence, the main objective of this thesis is to simulate the overall mass transfer phenomenon occurs in CAD-DES in the treatment of coronary artery disease. When a biodegradable coating (containing drug at the porous place of the coating) is given on the main structure of the stent, then this coating is degraded with time and drug releasing property from the stent also become changed. With degraded coating, the diffusion resistance of the drug is changed. At the same time the characteristic diffusion length and drug concentration also become changed. Thus, the thesis work focus on the change in coating resistance as well as the equilibrium drug concentration with respect to time and drug concentration changing due to changed equilibrium drug concentration with respect to time and position (radial) in the artery wall. These changes are observed by solving two partial differential equations for concentration and coating thickness where initial and boundary conditions are assumed. The simulated model is intended for the following specific aims:
- To show the decay of drug coating thickness (including the change in concentration of therapeutic drug in the coating) with time.
- To show the change in drug concentration in the artery tissue layer with time both in radial and longitudinal directions (i.e., a two-dimensional concentration profile).
- The model will finally be generalized incorporating an extra-component of drug mass transfer from the drug coating through the bare stent into the external blood flow in artery channel.
3.2 Research Significance:
The main target of this research work was to develop a model which will be able to predict drug mass transfer in CAD-DES. The significance or importance of this model has been briefly indicated below:
- The time taken by drug coating to decay completely can reasonably be determined using the simulated model. This will help to determine the safe working period of a drug eluting stent (DES). The model can be employed to study the effect of the properties of DES on their safe working period.
- The distribution of therapeutic drug molecules in the artery tissue along axial and radial directions after the release from stent can be studied using the simulated model. This will greatly help to evaluate the therapeutic performances of the various DES.
- The time taken by therapeutic drug molecules to cover the entire artery tissue can also reasonably be determined from the simulated model. This will help to evaluate the activity fastness of a DES.
- The simulated model can also be used to optimize several parameters related to DES and drug concentration profile.
Overall, the design, operation and performance of DES-based angioplasty would be benefited immensely from the present study.
Mass transport refers to the movement of mass, i.e. the species of interest which is drugs in the case of a DES, within a defined system. This transport of species may be provoked by concentration gradients between two points, but quite often in systems, especially in the vasculature, overpowering complex flow dynamics will ultimately be responsible for the mass transport outcome. In the absence of a free flowing system the presence of these concentration gradients induces diffusion, e.g. between the DES and the artery wall. Mass transport can be broken up into two types within the human vasculature. Firstly blood side mass transport (BSMT) refers to species transport within the vessel lumen and is subject to the hemodynamic therein. Often evanescent due to hemodynamic washout, BSMT can only be effective in transporting anti-proliferative agents to the wall in regions of high recirculation. The second, and most important, mode of mass transport is in relation to transport within the wall of the artery, referred to as wall side mass transport (WSMT). Along with the properties of the species being transported within the artery wall, WSMT depends on the structural condition of the wall itself, whereby a damaged intimal layer could facilitate accelerated mass transport through to the medial layer. WSMT can be governed by two transport forces, a pressure driven convective force and a diffusive force. The Peclet number (Pe) is a dimensionless parameter that can be used to determine the relative influences of these two forces. A small Pe (Pe1) indicates convection dominated mass transport.
4.1 Governing Equation of the Problem:
In the present thesis work, the main objective was to consider WSMT where drug concentration was evaluated with respect to time and position in artery wall. In this purpose, two drug mass transfer model was developed. In 1D model drug concentration has been evaluated with respect to time and radial position ® in the artery wall. In 2D model a drug concentration profile was developed with respect to time and radial ® and longitudinal position (z) in the artery wall. [.].
4.1.3 Artery Wall Classification:
Arteries transport oxygen rich blood around the body providing essential nutrients to vital organs. The artery wall consists of a complex multilayer porous substructure with an interstitial phase comprising predominantly of plasma. In a healthy artery this substructure(Fig.4.1) is comprised of three concentric layers; the tunica intima, the tunica media and the tunica adventitia. The tunica intima is the innermost layer, consisting of a single layer of endothelial cells and a sub endothelial layer mainly consisting of delicate connective tissues and collagen fibers. The outer boundary of the tunica intima is surrounded by an elastic tissue with fenestral pores known as the internal elastic lamina (IEL). The medial layer consists primarily of concentric sheets of smooth muscle cells (SMC) within a loose connective tissue framework. This configuration of SMC enables the artery wall to contract and relax. The tunica media and the tunica adventitia are separated by another thin band of elasticfibers known as the external elastic lamina (EEL). The outermost layer of the artery, the tunica adventitia, is comprised of connective tissue fibers and some capillaries. These fibers blend into the surrounding connective tissues and aid in stabilizing the arteries within the body. The target layer for the anti-restenotic drugs is the tunica media, because SMC resides here and possible erosion of the tunica intima occurs upon stent deployment.
The artery wall is porous in composition and drug transport is facilitated through the surrounding plasma not only via diffusion but there is also the presence of a trans-mural velocity due to a pressure gradient observed across the artery wall. However, the presence of arterial plaque will reduce the magnitude of this trans-mural velocity and can even stem it altogether. As DES is deployed in highly occluded arteries it is reasonable to reduce the complexity of the problem by neglecting convection in the wall. Equation 4.14 gives us an indication of how arterial properties such as porosity, tortuosity and free diffusivity can influence the transport of drugs within the respective artery wall layers. The compression of these layers will alter these properties which in turn may inhibit the transport of species as governed by the mass transport equations. The compression of a porous structure not only reduces the materials porosity but it results in the creation of a more arduous pore path over which mass transport would normally occur. The combination of a reduced porosity with an increased tortuosity, when the artery wall has been compressed, has a net effect of reducing the effective diffusivity thus hindering mass transport within the vessel.
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