Barry M O'Connell’s research while affiliated with University of Limerick and other places

The emergence of drug-eluting stents (DES) as a viable replacement for bare metal stenting has led to a significant decrease in the incidence of clinical restenosis. This is due to the transport of anti-restenotic drugs from within the polymer coating of a DES into the artery wall which arrests the cell cycle before restenosis can occur. The efficacy of DES is still under close scrutiny in the medical field as many issues regarding the effectiveness of DES drug transport in vivo still exist. One such issue, that has received less attention, is the limiting effect that stent strut compression has on the transport of drug species in the artery wall. Once the artery wall is compressed, the stents ability to transfer drug species into the arterial wall can be reduced. This leads to a reduction in the spatial therapeutic transfer of drug species to binding sites within the arterial wall. This paper investigates the concept of idealised variable compression as a means of demonstrating how such a stent design approach could improve the spatial delivery of drug species in the arterial wall. The study focused on assessing how the trends in concentration levels changed as a result of artery wall compression. Five idealised stent designs were created with a combination of thick struts that provide the necessary compression to restore luminal patency and thin uncompressive struts that improve the transport of drugs therein. By conducting numerical simulations of diffusive mass transport, this study found that the use of uncompressive struts results in a more uniform spatial distribution of drug species in the arterial wall.

The development and use of drug eluting stents has brought about significant improvements in reducing in-stent restenosis, however, their long term presence in the artery is still under examination due to restenosis reoccurring. Current studies focus mainly on stent design, coatings and deployment techniques but few studies address the issue of the physics of three dimensional mass transport in the artery wall. There is a dearth of adequate validated numerical mass transport models that simulate the physics of diffusion dominated drug transport in the artery wall whilst under compression. A novel experimental setup used in a previous study was adapted and an expansion of that research was carried out to validate the physics of three dimensional diffusive mass transport into a compressed porous media. This study developed a more sensitive method for measuring the concentration of the species of interest. It revalidated mass transport in the radial direction and presented results which highlight the need for an evaluation of the governing equation for transient diffusive mass transport in a porous media, in its current form, to be carried out.

This study assesses the suitability of developing a material for use in an experimental model of the carotid baroreceptors. Such a model could then be used in future studies to assess the impact of carotid artery stenting on hemodynamic stability. The material must exhibit a significant measurable electrical response to strain in a fashion analogous to baroreceptor behaviour. A modified electrically conductive silicone (ECS) was examined for use as the material, which was generated from a combination of Wacker LR 3162 and silicone thinner. Samples of the ECS were subjected to uniaxial tensile testing and electrical stimulation in order to mechanically and electrically characterise the material. Testing revealed that the ECS exhibits mechanical behaviour comparable to published data on carotid arterial tissue up to 20% strain and a measurable electrical response to strain in a fashion qualitatively comparable to baroreceptor behaviour. These findings highlight the potential of this material for employment as an experimental model of the carotid baroreceptors.

The development of atherosclerosis in the carotid bifurcation of the cardiovascular system has been the subject of much investigation. The carotid bifurcation is a prevalent area for atherosclerotic plaque build-up (Sakata et al., 1988). The performance of minimally invasive treatment of this plaque build-up has been below expectations. There is an increased need to analyse the poor performance of this treatment by numerically and experimentally replicating the diseased carotid bifurcation geometry with realistic material behaviour. This paper presents the investigation of an analogue material to represent arterial tissue behaviour. The aim of this study is to computationally set up an idealised carotid bifurcation model and compare the mechanical behaviour of arterial tissue and a silicone material model.

Carotid endarterectomy (CEA) is currently accepted as the gold standard for interventional revascularisation of diseased arteries belonging to the carotid bifurcation. Despite the proven efficacy of CEA, great interest has been generated in carotid angioplasty and stenting (CAS) as an alternative to open surgical therapy. CAS is less invasive compared with CEA, and has the potential to successfully treat lesions close to the aortic arch or distal internal carotid artery (ICA). Following promising results from two recent trials (CREST; Carotid revascularisation endarterectomy versus stenting trial, and ICSS; International carotid stenting study) it is envisaged that there will be a greater uptake in carotid stenting, especially amongst the group who do not qualify for open surgical repair, thus creating pressure to develop computational models that describe a multitude of plaque models in the carotid arteries and their reaction to the deployment of such interventional devices. Pertinent analyses will require fresh human atherosclerotic plaque material characteristics for different disease types. This study analysed atherosclerotic plaque characteristics from 18 patients tested on site, post-surgical revascularisation through endarterectomy, with 4 tissue samples being excluded from tensile testing based on large width-length ratios. According to their mechanical behaviour, atherosclerotic plaques were separated into 3 grades of stiffness. Individual and group material coefficients were then generated analytically using the Yeoh strain energy function. The ultimate tensile strength (UTS) of each sample was also recorded, showing large variation across the 14 atherosclerotic samples tested. Experimental Green strains at rupture varied from 0.299 to 0.588 and the Cauchy stress observed in the experiments was between 0.131 and 0.779 MPa. It is expected that this data may be used in future design optimisation of next generation interventional medical devices for the treatment and revascularisation of diseased arteries of the carotid bifurcation.

Coronary artery disease (CAD), which results in inadequate blood flow to the heart, is responsible for 1 in every 4.8 deaths in the USA (Lloyd-Jones et al., 2009). Currently, there are 16.5 million patients with stable angina and 500,000 new diagnoses annually (Gibbons et al., 2003). CAD has been linked with atherosclerosis since the early 20th century (McMahan et al., 2008) and refers to the localisation of the disease in the coronary arteries. Atherosclerosis is a degenerative disease that affects not only the coronary arteries, but also the carotid and other peripheral arteries in the body.

The development of restenosis within the coronary arteries after a stenting procedure has been addressed with the development of the drug eluting stent device. However, in recent times the superiority of the drug eluting stent over bare metal stents has been brought into question. A lack of knowledge regarding the behavior of drug transport from the drug eluting devices contributes to this uncertainty. Questions arise as to whether drug eluting stents deliver sufficient amounts of therapeutic agents into the artery wall to suppress restenosis. Published investigations in this area have focused primarily on trends associated with how variations in stenting conditions affect mass transport behavior. However, experimentally validated numerical models that simulate mass transport within the artery wall are lacking. A novel experimental model was developed to validate computational predictions of species diffusion into a porous medium and an investigation into how stent strut compression influences mass transport was conducted. The study revealed that increased compressive forces on a porous media reduced the ability of species to diffuse through that media, and in relation to drug eluting stents will contribute to a reduction in therapeutic levels of drugs within the wall.

Coronary artery disease can be treated by implanting a stent into the blocked region of an artery, thus enabling blood perfusion to distal vessels. Minimally invasive procedures of this nature often result in damage to the arterial tissue culminating in the re-blocking of the vessel. In an effort to alleviate this phenomenon, known as restenosis, drug eluting stents were developed. They are similar in composition to a bare metal stent but encompass a coating with therapeutic agents designed to reduce the overly aggressive healing response that contributes to restenosis. There are many variables that can influence the effectiveness of these therapeutic drugs being transported from the stent coating to and within the artery wall, many of which have been analysed and documented by researchers. However, the physical deformation of the artery substructure due to stent expansion, and its influence on a drugs ability to diffuse evenly within the artery wall have been lacking in published work to date. The paper highlights previous approaches adopted by researchers and proposes the addition of porous artery wall deformation to increase model accuracy.

Atherosclerosis is a degenerative disease that affects coronary, carotid and other peripheral arteries in the body. Arterial occlusions ensuing from aggressive atherosclerotic plaque progression can often culminate in an ischemic attack, such as an apoplectic attack or a myocardial infarction [1–3]. Several interventional procedures are available to the clinician but in recent years drug eluting stents (DES) have become the preferred choice and by the beginning of 2006 more than 8 out of 10 coronary stents were DES [4] at a cost of between $4 and$5 billion annually [5].