Healthy Arteries Research Articles

Impact of the confluence of cardiac motion and high spatial resolution on performance of ECG-gated imaging with an investigational photon-counting CT system: A phantom study

PurposePhoton-counting CT (PCCT) has higher spatial resolution that conventional EID CT which improves imaging of stationary coronary plaques and stents.. In this work, we evaluated the relationship between higher spatial resolution and motion acquisition on an investigational PCCT system. MethodsAn investigational photon-counting CT scanner (Siemens CounT) with ECG gating was used to image a coronary tree phantom with models of healthy, stenotic, and stented arteries using a motion simulator. Images were acquired with matched clinical parameters at rest and 60 beats per minute. An additional set of high dose stationary images were averaged to generate a motion-free, reduced noise reference. Scans were completed at standard (0.5 mm2) and high-resolution (0.25 mm2). Motion images were reconstructed at multiple phases. Regions of interest were drawn around vessels and segmented. Percentage difference from the reference standard was evaluated for vessel diameter and circularity. Mutual information between the reference and stationary and motion datasets was used as a measure of volumetric similarity. ResultsThe stenotic vessel showed the most variation from the reference when compared to healthy or stented vessels. Compared to standard resolution, high-resolution images had lower bias for diameter (-0.012 ± 0.19% vs −0.052 ± 0.14%) and lower variability for circularity (-0.13 ± 0.138% vs −0.12 ± 0.144%). Both differences were found to be statistically significant. High-resolution images had a slightly lower mutual information (1.28) than standard resolution (1.31). ConclusionThe higher spatial resolution enabled by photon-counting CT can be harnessed for cardiac imaging as the benefits of high spatial resolution acquisitions remain relevant in the presence of motion.

Assessment of pulmonary artery stiffness by multiparametric cardiac magnetic resonance-surrogate for right heart catheterization.

Cardiac magnetic resonance (CMR) imaging allows for multiparametric assessment of healthy pulmonary artery (PA) hemodynamics. Gender- and aging-associated PA stiffness and pressure alterations have remained clinically unestablished, however may demonstrate epidemiological differences in disease development. The aim of this study is to evaluate the role of CMR as a surrogate for catheter examinations by providing a comprehensive CMR assessment of sex- and age-related reference values for PA stiffness, flow, and pressure. PA hemodynamics were studied between gender and age groups (>/<50 years) using phase-contrast CMR. Corresponding correlation analyses were performed. 179 healthy volunteers with a median age of 32.6 years (range 11.3-68.2) were examined. Males demonstrated increased PA compliance (median [interquartile range] or mean ± standard deviation) (20.8 mm2/mmHg [16.6; 25.8] vs. 19.2 ± 7.1 mm2/mmHg; P < 0.033), higher pulse wave velocity (2.00 m/s [1.35; 2.87] vs. 1.73 m/s [1.19; 2.34]; P = 0.018) and a reduced full width half maximum (FWHM) (219 ± 22 ms vs. 235 ± 23 ms; P < 0.001) than females. Mean, systolic, diastolic PA pressure and pulmonary proportional pulse pressure were significantly elevated for males compared to females (P < 0.001). Older subjects (>50 years) exhibited reduced PA elasticity (41.7% [31.0; 52.9] vs. 66.4% [47.7; 83.0]; P < 0.001), reduced PA compliance (15.4 mm2/mmHg [12.3; 20.7] vs. 21.3 ± 6.8 mm2/mmHg; P < 0.001), higher pulse wave velocity (2.59 m/s [1.57; 3.59] vs. 1.76 m/s [1.24; 2.34]; P < 0.001) and a reduced FWHM (218 ± 29 ms vs. 231 ± 21 ms; P < 0.001) than younger subjects. Velocity-time profiles are dependent on age and gender. PA stiffness indices deteriorate with age. CMR has potential to serve as a surrogate for right heart catheterization.

10-channel phased-array coil for carotid wall MRI at 3T.

Accurate assessment of plaque accumulation near the carotid bifurcation is important for the effective prevention and treatment of stroke. However, vessel and plaque delineation using MRI can be limited by low contrast-to-noise ratio (CNR) and long acquisition times. In this work, a 10-channel phased-array receive coil design for bilateral imaging of the carotid bifurcation using 3T MRI is proposed. The proposed 10-channel receive coil was compared to a commercial 4-channel receive coil configuration using data acquired from phantoms and healthy volunteers (N = 9). The relative performance of the coils was assessed, by comparing signal-to-noise ratio (SNR), noise correlation, g-factor noise amplification, and the CNR between vessel wall and lumen using black-blood sequences. Patient data were acquired from 12 atherosclerotic carotid artery disease patients. The 10-channel coil consistently provided substantially increased SNR in phantoms (+77 ± 27%) and improved CNR in healthy carotid arteries (+62 ± 11%), or reduced g-factor noise amplification. Patient data showed excellent delineation of atherosclerotic plaque along the length of the carotid bifurcation using the 10-channel coil. The proposed 10-channel coil design allows for improved visualization of the carotid arteries and the carotid bifurcation and increased parallel imaging acceleration factors relative to a commercial 4-channel coil design.

Poor Below Knee Runoff Impacts Femoropopliteal Stent Failure and Fluoropolymer Antithrombotic Effect in Healthy Swine Model

Poor below knee (BTK) runoff is a predictor of stent failure after endovascular femoropopliteal artery treatment; however, lack of pathological evaluation has prevented characterisation of stent failure. The study aimed to investigate the impact of poor BTK runoff and the antithrombotic effect of the polymer of fluoropolymer coated paclitaxel eluting stents (FP-PESs) in a healthy swine femoropopliteal artery model. FP-PESs and bare metal stents (BMSs) and FP-PES and polymer free paclitaxel coated stents (PF-PCSs) were implanted in the bilateral femoral arteries of healthy swine (n= 6, respectively) following coil embolisation in both tibial arteries to induce poor BTK runoff. Histological assessment and intravascular imaging device evaluation were performed at one month. The Japanese Association for Laboratory Animal Science approved the study protocol (reference number: IVT22-90). Optical coherence tomography showed significantly lower percent area stenosis in FP-PES compared with BMS (37.3%, [interquartile range (IQR), 25.6-54.3] % vs. 92.5%[IQR, 75.5 - 96.1] %, respectively, p= .031), and PF-PCS (8.3%[IQR, 4.5 - 27.0] % vs. 31.2%[IQR, 23.3 - 52.2] %, respectively, p= .031). Histopathological evaluation demonstrated that thin fibrin attachment without re-stenosis was the most dominant neointimal tissue characteristic in FP-PES. On the other hand, neointimal tissue characteristics with significant restenosis of BMS and PF-PCS were mainly organising or organised thrombus. Organising and or organised thrombus attachment due to poor BTK runoff was the main cause of in stent restenosis of the swine femoral artery. FP-PES demonstrated the least percent area stenosis, suggesting the importance of the antithrombotic effect of polymer.

Economic evaluation and analysis of the budget effect of the measuring of fractional flow reserve in Bulgaria

Introduction: Fractional fl ow reserve (FFR) implies the ratio of the maximal hyperemic myocardial blood fl ow in the case of a pathologically changed coronary artery to the maximal hyperemic myocardial blood fl ow in the case of a healthy coronary artery. Aims: The aim of the current study is to perform an economic evaluation and budget impact analysis of measuring FFR as a medical activity in Bulgaria. Material and Methods: For the purpose of the current analysis, two models using Microsoft Excel and TreeAge Pro were developed to evaluate the cost-effectiveness of the FFR-guided percutaneous coronary intervention (PCI) compared to the classic angiography-guided PCI in patients with ischemic heart disease (IHD) with one-vessel coronary artery disease (CAD) or multivessel CAD. The analysis will focus on the health perspective and the payer perspective - National Health Insurance Fund (NHIF). Results: The medico-diagnostic activity related to measuring FFR in patients with multi-vessel coronary artery disease is shown to be a cost-effective therapeutic approach in Bulgaria compared to the angiography-guided PCI (ICER = 50 456 BGN/QALY) with a cost-effectiveness threshold of 51 510 BGN/QALY. FFR- guided PCI strategy in one-vessel coronary artery disease patients is a cost-saving approach (-853 BGN) when compared to the angiography-guided PCI (4 150 BGN). Conclusion: Budget impact analysis revealed that the FFR-guided PCI strategy is a cost-saving alternative approach to the angiographyguided PCI. The savings of the NHIF during the fi rst year of reimbursement of FFR would be -1,1 million BGN and could reach -1,6 million BGN in the third year.

Enteral administration of the protease inhibitor gabexate mesilate preserves vascular function in experimental trauma/hemorrhagic shock

Preserving vascular function is crucial for preventing multiorgan failure and death in ischemic and low-pressure states such as trauma/hemorrhagic shock (T/HS). It has recently been reported that inhibiting circulating proteases released from the bowel to the circulation during T/HS may preserve vascular function and improve outcomes following T/HS. This study aimed to evaluate the role of the serine protease inhibitor gabexate mesilate (GM) in preserving vascular function during T/HS when given enterally. We studied the vascular reactivity of mesenteric arteries from male Wistar rats treated with enteral GM (10 mg/kg) (GM-treated, n = 6) or control (Shock-control, n = 6) following (T/HS) using pressure myography. Concentration–response curves of endothelial-dependent and endothelial-independent agonists (e.g., acetylcholine, sodium nitroprusside) ranging from 10−10 to 10−5 M were performed. In a second set of experiments, ex-vivo arteries from healthy rats were perfused with plasma from shocked animals from both groups and vascular performance was similarly measured. Arteries from the GM-treated group demonstrated a preserved concentration–response curve to the α1 adrenergic agonist phenylephrine compared to arteries from Shock-control animals (− logEC50: − 5.73 ± 0.25 vs. − 6.48 ± 0.2, Shock-control vs. GM-treated, p = 0.04). When perfused with plasma from GM-treated rats, healthy arteries exhibited an even greater constriction and sensitivity to phenylephrine (− logEC50: − 6.62 ± 0.21 vs. − 7.13 ± 0.21, Shock-control vs. GM-treated, p = 0.02). Enteral GM also preserved the endothelium-dependent vascular response to agonists following T/HS and limited syndecan-1 shedding as a marker of glycocalyx compromise (41.84 ± 9 vs. 17.63 ± 3.97 ng/mL, Shock-control vs. GM-treated, p = 0.02). Syndecan-1 cleavage was correlated with plasma trypsin-like activity (r2 = 0.9611). Enteral gabexate mesilate was able to maintain vascular function in experimental T/HS, which was reflected by improved hemodynamics (mean arterial pressure 50.39 ± 7.91 vs. 64.95 ± 3.43 mmHg, Shock-control vs. GM treated, p = 0.0001). Enteral serine protease inhibition may be a potential therapeutic intervention in the treatment of T/HS.

Conventional Platinum Metal Implants Provoke Restenosis Responses in Atherogenic but Not Healthy Arteries

Platinum-containing stents are commonly used in humans with hypercholesterolemia, whereas preclinical stent evaluation has commonly been performed in healthy animal models, providing inadequate information about stent performance under hypercholesterolemic conditions. In this investigation, we used an ApoE−/− mouse model to test the impact of hypercholesterolemia on neointima formation on platinum-containing implants. We implanted 125 μm diameter platinum wires into the abdominal aortas of ApoE−/− and ApoE+/+ mice for 6 months, followed by histological and immunofluorescence examination of neointimal size and composition. It was found that ApoE−/− mice developed neointimas with four times larger area and ten times greater thickness than ApoE+/+ counterparts. Neointimas developed in the ApoE−/− mice also contained higher amounts of lipids quantified as having 370 times more coverage compared to ApoE+/+, a 3-fold increase in SMCs, and a 22-fold increase in macrophages. A confluent endothelium had regenerated in both mouse strains. The ApoE−/− mice experienced luminal reductions more closely resembling clinically relevant restenosis in humans. Overall, the response to platinum arterial implants was highly dependent upon the atherogenic environment.

On the descriptive and predictive capabilities of two model approaches considering the collagen fiber dispersion in healthy and aneurysmal arteries

Most constitutive models aim to describe the arterial macroscopic mechanical behavior via an elastin-rich ground substance reinforced by spatially dispersed collagen fibers. Two approaches are frequently considered for modeling collagen fiber dispersion, one is based on the generalized structure tensor (GST), and the other uses the angular integration (AI) method. Recently, both approaches have been reviewed for non-symmetric fiber distributions. It was concluded that both model ‘predictions’ fit very well with experimental data, solely based on the ability to ‘describe’ the same uniaxial or equibiaxial data set used for parameter estimation by not addressing any ‘predictive’ aspects. Therefore, this study systematically analyzes the ‘descriptive’ and ‘predictive’ capabilities of the GST and AI approaches by fitting their parameters to multiratio biaxial tensile test data of healthy and aneurysmal abdominal arteries. Subsequently, both model responses are investigated under realistic in vivo loading conditions, considering residual stresses, an axial in vivo stretch, and physiological blood pressure levels. In summary, no statistically significant difference in the ‘descriptive’ features of the two modeling approaches was identified. The pressure-radius relationship, the transmural stress distributions, and the axial force predicted by both models were analyzed for the healthy and diseased arterial ring, showing minor deviations based on fitting limitations.

RISK FACTORS FOR ARTERIAL STIFFNESS IN ADOLESCENCE

Objective: To investigate the arterial stiffness and risk factors in adolescence. Arterial stiffness often (AS) results from the degenerative process of the media layer of elastic arteries causing rigidity of the arteries. Arterial stiffness increases with age and it is associated with several risk factors as a disease predictor. But, arterial stiffness can be also increased in a healthy arteries as well. The increased sympathetic activity promotes vasoconstriction of resistant blood vessels i.e. arteries and arterioles that result in peripheral vasoconstriction. Adolescence age is the most important period of life for promoting future health. The certain dynamic risk factors in adolescence like, emotional dysregulation, psychological family stress, education pressure, lack of sleep, gambling, substance abuse, smartphone overuse and obesity can cause arterial stiffness. Design and method: The prospective open randomized study was designed. Adolescence age between 10 and 19 years have been investigated for increased arterial stiffness and risk factors. The inclusion criteria was healthy adolescence, while exclusion criteria was any disorder present. Arterial stiffness, non-invasive blood pressure and pulse wave datas have been measured using Agedio device. The risk factors were evaluated in every subject. The vascular age have been outlined as the final measure. Results: The preliminary results indicate the increase of Augmentation Index and Coefficient of Reflection. The average percentage of Augmentation Index was 40% and Coefficient of Reflection 65% (normal value 28% and 60% respectively). The main risk factors were educational pressure, lack of sleep and smartphone influence. The vascular age was on average, 3 years higher than biological age. Conclusions: Arterial stiffness in adolescence is increased mainly by peripheral vasoconstriction, manifested with Augmentation index and Coefficient of wave Reflection.

Effect of heart rate on the hemodynamics in healthy and stenosed carotid arteries

Stenosis in the internal carotid arteries is a serious cardiovascular condition. It is well-reported that low and oscillatory wall shear stress enhances the risk of stenosis progression. However, the effects of increased heart rates in highly stenosed arteries are not well explored. A detailed understanding of the flow features and stress distribution in stenosed carotid arteries at different heart rates may help clinicians to prescribe better exercise schedules for patients. In this study, we probe the effects of elevated heart rates on the hemodynamics in healthy and stenosed carotid arterial geometries using an immersed boundary method-based computational framework. Our results reveal that a strong recirculation, secondary velocity, and oscillatory shear index (OSI) zone develop inside a severely stenosed carotid artery at normal heart rate. Higher heart rates may potentially improve arterial health by reducing OSI only for the healthy and mild stenosis carotid arteries. However, the increased heart rates worsen the arterial health of severely stenosed arteries by onsetting flow instabilities, enhancing the spread and severity of the recirculation zone and the magnitude of the secondary velocity, the pressure drops across the stenosis, and the spread of high OSI (≥0.2) zone downstream. Furthermore, in the case of severe stenosis, the wall shear stress at the stenosis throat rises significantly, which can contribute to plaque rupture and thrombus development. Here, we report in detail the behavior of stress levels and pressure fluctuations in the carotid artery model at different stenosis levels for normal and elevated heart rates.

Abstract 101: Crosstalk Of Pluripotency And Innate Immunity In Smooth Muscle Cell Phenotypic Transitions

Objectives: Smooth muscle cell ( SMC ) phenotypic transitions play a critical role in the pathogenesis of cardiovascular diseases. However, the molecular mechanisms responsible for these transitions are not well understood. We previously found that the embryonic stem cell/pluripotency factor OCT4 is reactivated in SMC in human and mouse atherosclerotic plaques and plays an atheroprotective role by regulating SMC investment into the protective fibrous cap. Loss of OCT4 in SMC is associated with SMC de-differentiation toward a macrophage-like phenotypic state resulting in increased lipid accumulation and phagocytosis. However, the endogenous molecular mechanism responsible for atheroprotective SMC-OCT4-dependent effects remains unknown. Methods and Results: Herein, we performed combinatory bioinformatics analyses on the in vivo and in vitro wild-type and SMC- Oct4 knockout mouse samples and found that loss of Oct4 in SMC resulted in up-regulation of the innate immune receptor TLR4 in numerous experimental conditions. Notably, the TLR4 promoter does not have any putative OCT4 binding sites. First - Using publicly available OCT4 ChIPseq datasets and long non-coding ( lnc )RNA databases, we identified several lncRNAs, including IGF2AS, MALAT1, PLATR10, BACE1, and SRA based on the OCT4 occupancy at promoter and enhancer regions of lncRNA, which in turn, directly target TLR4. To confirm the OCT4-dependent activation of the identified lncRNAs in SMC, qRT-PCR was performed in mouse aortic SMC transfected with Oct4 -blocking siRNA. We found that the Oct4 knockdown in SMC led to significant decreases in all five selected lncRNAs and increases in TLR4 and its downstream gene, TRIF. Second - Intriguingly, we also demonstrated that TLR4 signaling, in turn, promotes hydroxymethylation of the OCT4 promoter and reactivates OCT4 in SMC. Third - Using a Tlr4 -reporter and SMC-lineage tracing mouse model, we also demonstrated that medial differentiated SMC from healthy arteries, but not phenotypically modulated lesion SMC, express TLR4. Conclusions: Together, these results indicate a role of TLR4-signaling in SMC both upstream and downstream of OCT4, suggesting that pluripotency/innate immunity crosstalk plays a critical role in SMC phenotypic transitions.

Wall Shear Stress Distribution of non-Newtonian Blood Flow in Stenosed Bifurcated Artery

Localized plaque causes narrowing of the arterial wall, resulting in an alteration in the flow structure, reducing the flow of fluids reaching the heart and resulting in heart attacks. The formation of stenosis could disturb the normal hemodynamics in blood rheology. A bifurcated artery with different types of stenosis is considered in order to illustrate the four possible formations of plaque between healthy and diseased arteries. Due to the fact that a diseased artery is reported to be less compliant, the artery wall is modelled as a two-dimensional rigid wall. In this model, blood flow is assumed to be steady, laminar, incompressible, and characterized as a generalized power-law model that is non-Newtonian in nature. The numerical simulation is performed using COMSOL Multiphysics, which is based on finite element method. Based on simulation results, different types of stenosis in the bifurcated artery have a significant impact on velocity profiles and wall shear stresses.

Translation of atherosclerotic disease features onto healthy carotid ultrasound images using domain-to-domain translation

ObjectiveIn this work, we evaluated a model for the translation of atherosclerotic disease features onto healthy carotid ultrasound images. MethodsAn un-paired domain-to-domain translation model – the cycle Generative Adversarial Network (cycleGAN) – was trained to translate between carotid ultrasound images of healthy arteries and images of pronounced disease. Translation performance was evaluated using the measurement of wall thickness in original and generated images. In addition, we explored disease translation in different tissue segments (subcutaneous tissue, muscle, lumen, far wall, and deep tissues), using structural similarity index measure (SSIM) maps. ResultsFeatures of pronounced disease were successfully translated to the healthy images (1.2 (0.33) mm vs 0.43 (0.07) mm, p < 0.001), while overall anatomy was retained as SSIM value was equal to 0.78 (0.02). Exploration of translated features showed that both arterial wall and subcutaneous tissues were modified in the translation, but that the subcutaneous tissue was subject to distortion of the anatomy in some cases. The image quality influenced the disease translation performance. ConclusionThe results show that the model can learn a mapping between healthy and diseased images while retaining the overall anatomical contents. This is the first study on atherosclerosis disease translation in medical images. SignificanceThe concept of translating disease onto existing healthy images may serve purposes such as education, cardiovascular risk communication in health conversations, or personalized modelling in precision medicine.

Integrated single-cell RNA-seq analysis reveals the vital cell types and dynamic development signature of atherosclerosis.

Introduction: In the development of atherosclerosis, the remodeling of blood vessels is a key process involving plaque formation and rupture. So far, most reports mainly believe that macrophages, smooth muscle cells, and endothelial cells located at the intima and media of artery play the key role in this process. Few studies had focused on whether fibroblasts located at adventitia are involved in regulating disease process. Methods and results: In this study, we conducted in-depth analysis of single-cell RNA-seq data of the total of 18 samples from healthy and atherosclerotic arteries. This study combines several analysis methods including transcription regulator network, cell-cell communication network, pseudotime trajectory, gene set enrichment analysis, and differential expression analysis. We found that SERPINF1 is highly expressed in fibroblasts and is involved in the regulation of various signaling pathways. Conclusion: Our research reveals a potential mechanism of atherosclerosis, SERPINF1 regulates the formation and rupture of plaques through the Jak-STAT signaling pathway, which may provide new insights into the pathological study of disease. Moreover, we suggest that SRGN and IGKC as potential biomarkers for unstable arterial plaques.

In vivo evaluation of intravascular lithotripsy in a healthy porcine coronary model

In this study, we aimed to investigate the vascular response to an intravascular lithotripsy (IVL) shockwave balloon in a healthy porcine coronary artery model. IVL is a novel clinical technique for modifying heavily calcified atherosclerotic plaques. A total of 24 porcine coronary arteries were treated with IVL or plain old balloon angioplasty (POBA). Histology, histomorphometry, quantitative coronary angiography analysis (QCA), and optical coherence tomography (OCT) were performed postprocedure and at 1-month follow-up (1M-FU). There was no significant difference in the late lumen loss and diameter stenosis (determined by QCA) and the minimal lumen area (evaluated by OCT) of the IVL and POBA groups at 1M-FU. Pathological analysis revealed that the lumen and neointima areas were similar between the two groups. However, the medial and adventitial layers were more prominent in the IVL than in the POBA group. The injury score and inflammation of the media and adventitia increased dramatically in the IVL group postprocedure and at 1M-FU. At 1M-FU, media fibrin deposition and adventitial fibrosis were also significantly increased in the IVL group. However, there was no significant difference in neointima fibrin deposition, endothelialization, and thrombosis between both groups. Layered separation of the media and adventitia was observed in the IVL group. The findings indicate that the IVL balloon did not cause serious intimal hyperplasia and endothelial damage compared with the effects of POBA in the healthy coronary artery. However, shock waves may cause unique damage to the vascular media and adventitia in the coronary artery, which was not observed in the peripheral artery.

First steps towards modeling the interaction of cardiovascular agents and smooth muscle activation in arterial walls

AbstractNumerical simulation of the response of healthy and pathological arteries to cardiovascular agents can provide valuable information to the physician in the treatment of diseases such as hypertension, atherosclerosis, and the Marfan syndrome. Here, we provide a first step towards a computational framework to model the effects of antihypertensive agents on the mechanical response of arterial walls. A material model is developed by extending an existing formulation for wall tissue to incorporate the effects of calcium‐ion channel blockers. The resulting coupled deformation‐diffusion problem is then solved using the finite element method. Simulation results with drug activity show that, indeed, an increased lumen diameter due to reduced contraction is obtained. Additionally, a decrease in the rate of arterial contraction is observed, which is also consistent with expected behavior. Finally, we compare results for an implicit or explicit treatment of the the deformation‐diffusion coupling, and we observe that both coupling schemes yield comparable results for a wide range of time step sizes.

Analyzing coronary bifurcation structures: Towards personalized balloon angioplasty and stent deployment

Treating coronary artery disease in bifurcation lesions presents many practical challenges. Developing bifurcation specific devices and procedures may improve results. In order to further understand angiographic bifurcation features, a set of healthy coronary artery bifurcations were measured and evaluated in order to develop models to predict carina diameter and tapering length for a new balloon forming system

Inflation-induced bulge initiation and evolution in graded cylindrical tubes of arbitrary thickness

We study the initiation, evolution, and propagation of localized bulging in a pressurized heperelastic tube where the elastic modulus is non-uniform in the radial direction. The primary deformation prior to instability is characterized within the framework of nonlinear elasticity for a general material constitution and a generic modulus gradient. To unravel the influence of modulus gradient on localized bulging, we employ the incompressible Gent model and select three representative modulus gradients, including a linear, an exponential, and a sinusoidal function. In particular, the sinusoidal one is supposed to model an actual artery structure. In addition, two prototypical loading conditions are considered, namely, either the resultant axial force or the axial length can be fixed. Based on an explicit bifurcation condition in terms of the internal pressure and the resultant axial force for localized bulging, an exhaustive theoretical analysis on bulge initiation is carried out and the effect of geometric and material parameters and the modulus gradient on the critical stretch triggering localized bulging is revealed. It turns out that the modulus mismatch, as well as the position of maximum modulus, can dramatically affect the onset of localized bulging. Then we analytically elucidate the influence of modulus gradient on bulge propagation according to Maxwell’s equal area rule and conduct a finite element analysis of bulge evolution. To perform post-bifurcation analysis, a robust finite element model for graded Gent material is established in Abaqus by UHYPER subroutine coding. Interestingly, it is found that a sinusoidally distributed modulus has negligible influence on the critical stretch of bulge initiation, the deformation process of bugle growth, and the maximum size of a bulge. The current analysis not only can be used to qualitatively explain why a healthy human artery evolves into a sandwich structure where the intermediate layer is stiffest but also can provide useful insight into localized instabilities such as necking and beading in graded structures.

A coupled thermal-electrical-structural model for balloon-based thermoplasty treatment of atherosclerosis

Objectives The outcome of balloon-based atherosclerosis thermoplasty is closely related to the temperature/stress distribution during the treatment. For precise prediction of a required thermal lesion in the heterogeneous and thin atherosclerotic vessel, a numerical model incorporating heat-induced tissue expansion or shrinkage and the strain caused by balloon dilation is necessary. Methods A fully coupled thermal-electrical-structural new model was established. The model features a heterogeneous structure including eccentric plaque, healthy artery and surrounding tissue. Tissue expansion/shrinkage and hyperelasticity material model were taken into consideration. Different heating strategies and plaque mechanical properties were investigated. The temperature distribution was compared with the traditional thermal-electrical coupled model. The possibility of thermoplasty treatment using balloons with different sizes was also explored. Results The temperature, the electrical intensity and the stress during the thermoplasty were obtained. Lower stress was found in the heating region where tissue shrinkage occurred. The ablation depth was predicted to be ∼0.42 mm larger without coupling the biomechanical influence. The mechanical properties and input condition significantly affect the temperature and stress distribution considering the small dimensions of the tissue. Besides, with a 12.5% reduction of balloon diameter, the largest Von Mises stress decreases by 25.4%. Conclusions It is confirmed that a coupled thermal-electrical-structural model is needed for precise temperature prediction in the balloon-based thermoplasty of the heterogeneous and thin tissue. The model presented may help with future development of optimized treatment planning considering both ablation depth and minimum stress.

Increased Thromboxane A2 Levels in Pulmonary Artery Smooth Muscle Cells Isolated from Patients with Chronic Obstructive Pulmonary Disease.

Introduction: Pulmonary hypertension due to chronic obstructive pulmonary disease (COPD) is classified as Group 3 pulmonary hypertension, with no current proven targeted therapies. It has been shown that cigarette smoke, the main risk factor for COPD, can increase thromboxane A2 production in healthy human pulmonary artery smooth muscle cells and pulmonary artery endothelial cells, and that blocking the effect of increased thromboxane A2 using daltroban, a thromboxane A2 receptor antagonist, can inhibit cigarette smoke-induced pulmonary artery cell proliferation. However, it is largely unknown whether thromboxane A2 is increased in smokers with COPD. Therefore, the aim of this study was to assess the level of thromboxane A2 production in patients with COPD who smoke. Methods: Pulmonary artery smooth muscle cells from three smokers with COPD and three healthy donors were cultured in cell culture medium. The culture medium was collected and the thromboxane B2 (a stable metabolite of thromboxane A2) released in the culture medium was quantified using an ELISA kit. The data were normalised with the total protein concentration and then expressed in pg/mg protein. Demographic data were collected and baseline pulmonary function tests of patients with COPD were conducted. Results: The mean age of patients with COPD was 69 ± 7 years. All patients were smokers and had a mean smoking history of 39.66 ± 9.50 packs per year. The mean forced expiratory volume in one second, that is, FEV1%, and the ratio of forced vital capacity (FVC) to FEV1% of COPD patients were 63.33 ± 19.60% and 52.66 ± 14.64%, respectively. The results revealed that thromboxane A2 production was significantly increased in pulmonary artery smooth muscle cells from smokers with COPD (434.56 ± 82.88 pg/mg protein) compared with the thromboxane A2 levels in pulmonary artery smooth muscle cells from healthy donors (160 ± 59.3 pg/mg protein). Conclusions: This is the first report of increased thromboxane A2 production in pulmonary artery smooth muscle cells from smokers with COPD. This observation strongly suggests that thromboxane A2 can be used as a novel therapeutic target for the treatment of patients with COPD-associated pulmonary hypertension.