可降解冠状动脉支架的研究进展

冠脉内支架植入是临床上预防PTCA术后再狭窄并发症的有效措施,但金属支架仅在植入早期发生作用,在冠脉内壁修复完成后则成为多余的负担,可能激活血小板及多种凝血因子聚集导致血栓形成及刺激血管壁造成心脏事件及再狭窄的发生。针对上述问题,生物可降解冠状动脉支架的研究得到了相当的发展。本文就可降解支架的发展及现状作一简要综述。     

Developing pulsatile flow in a deployed coronary stent

A major consequence of stent implantation is restenosis that occurs due to neointimal formation. This patho-physiologic process of tissue growth may not be completely eliminated. Recent evidence suggests that there are several factors such as geometry and size of vessel, and stent design that alter hemodynamic parameters, including local wall shear stress distributions, all of which influence the restenosis process. The present three-dimensional analysis of developing pulsatile flow in a deployed coronary stent quantifies hemodynamic parameters and illustrates the changes in local wall shear stress distributions and their impact on restenosis. The present model evaluates the effect of entrance flow, where the stent is placed at the entrance region of a branched coronary artery. Stent geometry showed a complex three-dimensional variation of wall shear stress distributions within the stented region. Higher order of magnitude of wall shear stress of 530 dyn/cm2 is observed on the surface of cross-link intersections at the entrance of the stent. A low positive wall shear stress of 10 dyn/cm2 and a negative wall shear stress of -10 dyn/cm2 are seen at the immediate upstream and downstream regions of strut intersections, respectively. Modified oscillatory shear index is calculated which showed persistent recirculation at the downstream region of each strut intersection. The portions of the vessel where there is low and negative wall shear stress may represent locations of thrombus formation and platelet accumulation. The present results indicate that the immediate downstream regions of strut intersections are areas highly susceptible to restenosis, whereas a high shear stress at the strut intersection may cause platelet activation and free emboli formation.     

Numerical investigation of the intravascular coronary stent flexibility

Nowadays stent therapy is widely adopted to treat atherosclerotic vessel diseases. The high commercial value of these devices and the high prototypation costs require the use of finite element analyses, instead of classical trial and error technique, to design and verify new models. In this paper, we explore the advantages of the finite element method (FEM) in order to investigate new generation stent performance in terms of flexibility. Indeed, the ability of the stent to bend in order to accommodate curvatures and angles of vessels during delivery is one of the most significant prerequisites for optimal stent performance. Two different FEM models, resembling two new generation intravascular stents, were developed. The main model dimensions were obtained by means of a stereo microscope, analyzing one Cordis BX-Velocity and one Carbostent Sirius coronary stent. Bending tests under displacement control in the unexpanded and expanded configuration were carried out. The curvature index, defined as the ratio between the sum of rotation angles at the extremes and the length of the stent, yielded comparative information about the capability of the device to be delivered into tortuous vessels and to conform to their contours. Results, expressed in terms of the bending moment-curvature index, demonstrated a different response for the two models. In particular the Cordis model showed a higher flexibility. Lower flexibility in the expanded configurations for both models was detected. However this flexibility depends on how the contact takes place between the different parts of the struts.     

Developed pulsatile flow in a deployed coronary stent

The patho-physiologic process of restenosis and tissue growth may not be completely eliminated and is the primary concern of clinicians performing angioplasty and stent implantation procedures. Recent evidence suggests that the restenosis process is influenced by several factors: (1) geometry and size of vessel; (2) stent design; and (3) it's location that alter hemodynamic parameters, including local wall shear stress (WSS) distributions. The present three-dimensional (3D) analysis of pulsatile flow in a deployed coronary stent: (1) shows complex 3D variation of hemodynamic parameters; and (2) quantifies the changes in local WSS distributions for developed flow and compares with recently published WSS data for developing flow. Higher order of magnitude of WSS of 290 dyn/cm(2) is observed on the surface of cross-link intersections at the entrance of the stent for developed flow, which is about half of that for developing flow. Low WSS of 0.8 dyn/cm(2) and negative WSS of -8 dyn/cm(2) are seen at the immediate upstream and downstream regions of strut intersections. Persistent recirculation is observed at the downstream region of each strut cross-link and the regions of low and negative WSS may lead to patho-physiologic conditions near the stented region. The key finding of this study is that the location of stent in the coronary artery determines the developing or developed nature of the flow, which in turn, results in varied level of WSS.     

Expansion and drug elution model of a coronary stent

The present study illustrates a possible methodology to investigate drug elution from an expanded coronary stent. Models based on finite element method have been built including the presence of the atherosclerotic plaque, the artery and the coronary stent. These models take into account the mechanical effects of the stent expansion as well as the effect of drug transport from the expanded stent into the arterial wall. Results allow to quantify the stress field in the vascular wall, the tissue prolapse within the stent struts, as well as the drug concentration at any location and time inside the arterial wall, together with several related quantities as the drug dose and the drug residence times.     

Long-term clinical outcome after stent implantation in coronary arteries

The long-term clinical outcome after planned and unplanned stent implantation was assessed in a single-center, observational study in 178 patients who underwent coronary stent implantation between November 1986 and July 1994. Main outcome measures were survival and event-free survival at 5 years (Kaplan-Meier method). Independent predictors for event-free survival were determined by using multivariate logistic regression analysis. Patients underwent planned (group 1, n 3 101) or unplanned (group 2, n 3 77) stent implantation. During the in-hospital period, there were no deaths. The incidence of Q-wave and non-Q-wave acute myocardial infarction (AMI), coronary artery bypass graft (CABG) and repeat percutaneous transluminal coronary angioplasty (PTCA) was 5.0%, 2.0% and 4.0%, respectively, in group 1, versus 32.5%, 23.4% and 10.4%, respectively, in group 2. During the follow-up period (median 4.0 years, range 0.29-9.8 years), the incidence of death, AMI, and repeat revascularization (CABG and PTCA) was 5.9%, 8.9% and 40.6%, respectively, in group 1, versus 1.3%, 5.2% and 36.4%, respectively, in group 2. Survival and event-free survival at 5 years was 73 (7%) and 47 (7%), respectively, for patients who underwent planned stent implantation. It was 98 (0.1%) and 34 (6%), respectively, for patients who underwent unplanned stent implantation. At the end of follow-up, 31.9% of patients had angina pectoris class III or IV (Canadian Cardiovascular Society). The long-term clinical outcome after both planned and unplanned stent implantation was characterized by a high incidence of repeat revascularization. It is conceivable that changes in stent design and implantation techniques, in addition to novel therapeutic approaches addressing neointima formation and progression of atherosclerosis, may improve the long-term clinical outcome.     

Expansion and drug elution model of a coronary stent

The present study illustrates a possible methodology to investigate drug elution from an expanded coronary stent. Models based on finite element method have been built including the presence of the atherosclerotic plaque, the artery and the coronary stent. These models take into account the mechanical effects of the stent expansion as well as the effect of drug transport from the expanded stent into the arterial wall. Results allow to quantify the stress field in the vascular wall, the tissue prolapse within the stent struts, as well as the drug concentration at any location and time inside the arterial wall, together with several related quantities as the drug dose and the drug residence times.     

Sensor to detect endothelialization on an active coronary stent

Background  

A serious complication with drug-eluting coronary stents is late thrombosis, caused by exposed stent struts not covered by endothelial cells in the healing process. Real-time detection of this healing process could guide physicians for more individualized anti-platelet therapy. Here we present work towards developing a sensor to detect this healing process. Sensors on several stent struts could give information about the heterogeneity of healing across the stent.     

Use of Rtrade mark stent in the percutaneous coronary intervention of coronary bifurcation lesions

BACKGROUND: Percutaneous Coronary Intervention (PCI) of coronary bifurcation lesion is technically quite demanding. It has been associated with a lower procedural success, higher rates of complication and restenosis. Side-branch occlusion and plaque shifting or 'snow plow' effect are not uncommon. Stenting of the main vessel may cause 'stent jail' of the side-branch. Modern stent design may allow passage of a balloon or stent into the side-branch through the struts of the stent placed in the main vessel. A newly developed 316 stainless steel tubular stent, the Rtrade mark stent is uniquely designed to provide flexibility, radial strength on deployment and conformability. Its large cell size facilitates PCI of bifurcation lesion. AIM: To assess the feasibility of R(trade mark) stent in the treatment of symptomatic patients with bifurcation coronary lesions. The main objective was to assess the ease of deployment, side-branch access and overall success of the R(trade mark) stent in this group of patients without any major adverse events. METHODS: Between December 1998 and September 2000 the R(trade mark) stent was used as a main stent in 28 consecutive patients with coronary bifurcation lesions, 46% of which had unstable angina. The mean age was 59 +/- 10 and 89% were male. Adjunctive medical therapy included clopidrogel, aspirin and intraprocedure heparin. Abciximab (ReoPro) was given to 9 patients. RESULTS: Successful stent deployment was achieved in all patients. Thirty-four R Stents and 16 other stents were used. Two patients had post-procedure rise in cardiac enzymes. There were no major adverse events at 30 days. LAD/D1 with LAD/diagonal was the target lesion in the majority of patients. Stenting of the side-branch was done in 18 and balloon dilatation in 9 patients. At 3-23 months (mean 11.8) follow-up, repeat angiography was done in 18 patients with restenosis in 4, two of them had repeat PCI and one had coronary artery bypass graft (CABG). CONCLUSION: Coronary bifurcation lesions are not uncommon. Current advances in stent technology offer a safe and effective revascularisation strategy for such complex lesions. The R(trade mark) stent appears to be a suitable device that provides good wall coverage, radial strength, conformability and easy side-branch access.     

Simulation of stent deployment in a realistic human coronary artery

Background  

The process of restenosis after a stenting procedure is related to local biomechanical environment. Arterial wall stresses caused by the interaction of the stent with the vascular wall and possibly stress induced stent strut fracture are two important parameters. The knowledge of these parameters after stent deployment in a patient derived 3D reconstruction of a diseased coronary artery might give insights in the understanding of the process of restenosis.     

Computational structural modelling of coronary stent deployment: a review

The finite element (FE) method is a powerful investigative tool in the field of biomedical engineering, particularly in the analysis of medical devices such as coronary stents whose performance is extremely difficult to evaluate in vivo. In recent years, a number of FE studies have been carried out to simulate the deployment of coronary stents, and the results of these studies have been utilised to assess and optimise the performance of these devices. The aim of this paper is to provide a thorough review of the state-of-the-art research in this area, discussing the aims, methods and conclusions drawn from a number of significant studies. It is intended that this paper will provide a valuable reference for future research in this area.     

Gene delivery from a DNA controlled-release stent in porcine coronary arteries

Expandable intra-arterial stents are widely used for treating coronary disease. We hypothesized that local gene delivery could be achieved with the controlled release of DNA from a polymer coating on an expandable stent. Our paper reports the first successful transfection in vivo using a DNA controlled-release stent. Green fluorescent protein (GFP) plasmid DNA within emulsion-coated stents was efficiently expressed in cell cultures (7.9% +/- 0.7% vs. 0.6% +/- 0.2% control, p < 0.001) of rat aortic smooth muscle cells. In a series of pig stent-angioplasty studies, GFP expression was observed in all coronary arteries (normal, nondiseased) in the DNA-treated group, but not in control arteries. GFP plasmid DNA in the arterial wall was confirmed by PCR, and GFP presence in the pig coronaries was confirmed by immunohistochemistry. Thus, DNA-eluting stents are capable of arterial transfection, and could be useful as delivery systems for candidate vectors for gene therapy of cardiovascular diseases.     

Local hemodynamic analysis after coronary stent implantation based on Euler-Lagrange method

Coronary stents are deployed to treat the coronary artery disease (CAD) by reopening stenotic regions in arteries to restore blood flow, but the risk of the in-stent restenosis (ISR) is high after stent implantation. One of the reasons is that stent implantation induces changes in local hemodynamic environment, so it is of vital importance to study the blood flow in stented arteries. Based on regarding the red blood cell (RBC) as a rigid solid particle and regarding the blood (including RBCs and plasma) as particle suspensions, a non-Newtonian particle suspensions model is proposed to simulate the realistic blood flow in this work. It considers the blood’s flow pattern and non-Newtonian characteristic, the blood cell-cell interactions, and the additional effects owing to the bi-concave shape and rotation of the RBC. Then, it is compared with other four common hemodynamic models (Newtonian single-phase flow model, Newtonian Eulerian two-phase flow model, non-Newtonian single-phase flow model, non-Newtonian Eulerian two-phase flow model), and the comparison results indicate that the models with the non-Newtonian characteristic are more suitable to describe the realistic blood flow. Afterwards, based on the non-Newtonian particle suspensions model, the local hemodynamic environment in stented arteries is investigated. The result shows that the stent strut protrusion into the flow stream would be likely to produce the flow stagnation zone. And the stent implantation can make the pressure gradient distribution uneven. Besides, the wall shear stress (WSS) of the region adjacent to every stent strut is lower than 0.5 Pa, and along the flow direction, the low-WSS zone near the strut behind is larger than that near the front strut. What’s more, in the regions near the struts in the proximal of the stent, the RBC particle stagnation zone is easy to be formed, and the erosion and deposition of RBCs are prone to occur. These hemodynamic analyses illustrate that the risk of ISR is high in the regions adjacent to the struts in the proximal and the distal ends of the stent when compared with struts in other positions of the stent. So the research can provide a suggestion on the stent design, which indicates that the strut structure in these positions of a stent should be optimized further.