Stenosis Model Research Articles

Iron corroded granules inhibiting vascular smooth muscle cell proliferation.

In-stent restenosis after interventional therapy remains a severe clinical complication. Current evidence indicates that neointimal hyperplasia induced by vascular smooth muscle cell (VSMC) proliferation is a major cause of restenosis. Thus, inhibiting VSMC proliferation is critical for preventing in-stent restenosis. The incidence of restenosis was reduced in nitrided iron-based stents (hereafter referred to as iron stents). We hypothesized that the corroded granules produced by the iron stent would prevent in-stent restenosis by inhibiting VSMC proliferation. To verify this hypothesis, we introduced a dynamic circulation device to analyze the components of corroded granules. To investigate the effects of corroded granules on VSMC proliferation, we implanted the corroded iron stent into the artery of the atherosclerotic artery stenosis model. Moreover, we explored the mechanism underlying the inhibition of VSMC proliferation by iron corroded granules. The results indicated that iron stent produced the corroded granules after implantation, and the main component of the corrosion granules was iron oxide. Remarkably, the corroded granules reduced the neointimal hyperplasia in an atherosclerotic artery stenosis model, and iron corroded granules decreased the neointimal hyperplasia by inhibiting VSMC proliferation. In addition, we revealed that corroded granules reduced VSMC proliferation by activating autophagy through the AMPK/mTOR signaling pathway. Importantly, safety of iron corroded granules was evaluated and proved to be satisfactory hemocompatibility in rabbit model. Overall, the role of corroded granules in restenosis prevention was described for the first time. This finding highlighted the implication of corroded granules produced by iron stent in inhibiting VSMC proliferation, pointing to a new direction to prevent in-stent restenosis.

Importance of plaque volume and composition for the prediction of myocardial ischaemia using sequential coronary computed tomography angiography/positron emission tomography imaging.

Coronary atherosclerosis with a large necrotic core has been postulated to reduce the vasodilatory capacity of vascular tissue. In the present analysis, we explored whether total plaque volume and necrotic core volume on coronary computed tomography angiography (CCTA) are independently associated with myocardial ischaemia on positron emission tomography (PET). From a registry of symptomatic patients with suspected coronary artery disease and clinically indicated CCTA with sequential [15O]H2O PET myocardial perfusion imaging, we quantitatively measured diameter stenosis, total and compositional plaque volumes on CCTA. Primary endpoint was myocardial ischaemia on PET, defined as an absolute stress myocardial blood flow ≤2.4 mL/g/min in ≥1 segment. Multivariable prediction models for myocardial ischaemia were consecutively created using logistic regression analysis (stenosis model: diameter stenosis ≥50%; plaque volume model: +total plaque volume; plaque composition model: +necrotic core volume). A total of 493 patients (mean age 63 ± 8 years, 54% men) underwent sequential CCTA/PET imaging. In 153 (31%) patients, myocardial ischaemia was detected on PET. Diameter stenosis ≥50% (P < 0.001) and necrotic core volume (P = 0.029) were independently associated with myocardial ischaemia, while total plaque volume showed borderline significance (P = 0.052). The plaque composition model (χ2 = 169) provided incremental value for the prediction of ischaemia when compared with the stenosis model (χ2 = 138, P < 0.001) and plaque volume model (χ2 = 164, P = 0.021). The volume of necrotic core on CCTA independently and incrementally predicts myocardial ischaemia on PET, beyond diameter stenosis alone.

OC01.07: Development of a diagnostic model for fetal pulmonary valvular stenosis by myocardial strain combined with multiple ultrasonic parameters

OC01.07: Development of a diagnostic model for fetal pulmonary valvular stenosis by myocardial strain combined with multiple ultrasonic parameters

Impact of Serial Coronary Stenoses on Various Coronary Physiologic Indices

Determining the functional significance of each individual coronary lesion in patients with serial coronary stenoses is challenging. It has been proposed that nonhyperemic pressure ratios, such as the instantaneous wave free ratio (iFR) and the ratio of resting distal to proximal coronary pressure (Pd/Pa) are more accurate than fractional flow reserve (FFR) because autoregulation should maintain stable resting coronary flow and avoid hemodynamic interdependence (cross-talk) that occurs during hyperemia. This study aimed to measure the degree of hemodynamic interdependence of iFR, resting Pd/Pa, and FFR in a porcine model of serial coronary stenosis. In 6 anesthetized female swine, 381 serial coronary stenoses were created in the left anterior descending artery using 2 balloon catheters. The degree of hemodynamic interdependence was calculated by measuring the absolute changes in iFR, resting Pd/Pa, and FFR across the fixed stenosis as the severity of the other stenosis varied. The hemodynamic interdependence of iFR, resting Pd/Pa, and FFR was 0.039±0.048, 0.021±0.026, and 0.034±0.034, respectively (all P<0.001). When the functional significance of serial stenoses was less severe (0.70-0.90 for each index), the hemodynamic interdependence was 0.009±0.020, 0.007±0.013, and 0.017±0.022 for iFR, resting Pd/Pa, and FFR, respectively (all P<0.001). However, in more severe serial coronary stenoses (<0.60 for each index), hemodynamic interdependence was 0.060±0.050, 0.037±0.030, and 0.051±0.037 for iFR, resting Pd/Pa, and FFR, respectively (all P<0.001). When assessing serial coronary stenoses, nonhyperemic pressure ratios are affected by hemodynamic interdependence. When the functional significance of serial coronary stenoses is severe, the effect is similar to that which is seen with FFR.

Phasicity and resistance of the arterial spectral Doppler waveform in a canine femoral focal artery stenosis model.

This study aims to evaluate changes in the arterial spectral Doppler waveform in a canine artery stenosis model. Canine femoral artery stenosis models were established in 12 beagle dogs. Doppler waveforms were recorded in the femoral artery preoperatively and postoperatively in the femoral artery and at the ankle after formation of a 50%, 70%, and 90% stenosis or occlusion. Major descriptors for arterial Doppler waveform were used to analyse waveforms. The proportion of multiphasic waveforms proximal to a moderate stenosis decreased compared to normal baseline, although the difference was not statistically significant, whereas the decreases at the stenosis, distal to the stenosis, and at the ankle were significant (p < 0.05). The decreases in arteries with a more severe stenosis or occlusion were significant at all locations (p < 0.05). The proportion of high resistive waveforms decreased significantly at the ankle in the arteries with a moderate stenosis (50%) (p = 0.002), but the decreases proximal to, at, and distal to the stenosis were not significant. The decreases were significant at all locations in the arteries with a more severe stenosis (p < 0.05). The decrease was significant at the ankle in the arteries with an occlusion (p < 0.001) but not significant pre, at, and post an occlusion. Phasicity and resistance of Doppler waveforms alter in canine femoral arteries with a stenosis. Phasicity change seems more sensitive in response to an arterial stenosis than resistance change. Additional information on arterial resistance could be obtained using end-diastolic ratios, resistive indices, and potentially end-systolic notch velocity measurements.

Establishing a novel model of malignant airway stenosis in rabbit.

BackgroundMalignant central airway stenosis is a life-threatening condition. However, treatment of malignant airway stenosis remains challenging. There is currently a severe lack of an excellent animal model of malignant airway stenosis to facilitate treatment approaches. This is the first study to establish a rabbit model of malignant airway stenosis for bronchoscopic interventional studies.Materials and methodsNew Zealand White rabbits were used in this study, randomly divided into group A (18 rabbits) and group B (6 rabbits). A VX2 fragment suspension was injected into the submucosal layer of rabbits’ airway by bronchoscopy. Bronchoscopic examinations were performed once a week after VX2 tumor implantation to observe tumor growth and the degree of airway stenosis. Randomly, three rabbits were generally dissected after a weekly bronchoscopic examination in group A. The rabbits that reached grade III airway stenosis underwent stent implantation in group B.ResultsA total of 24 rabbits were successfully implanted with the VX2 fragment suspension in the airway without significant adverse events, and the success rate of the tumor growth was 100%. The degree of airway stenosis reaching grade III took 2 to 3 weeks after implantation of the VX2 tumor. The median survival time of rabbit models without stent implantation and rabbits with stent implantation was 32.5 and 32.0 days, respectively.ConclusionsThe implanting method is safe and effective for the establishment of a rabbit model of malignant airway stenosis. When the tumor grows to 2 to 3 weeks, the rabbit model is available for stent implantation. We recommend the models for more preclinical animal studies on bronchoscopic interventional treatments.

Effect of warfarin combined with B- mode ultrasound- guided photomechanical thrombolytic therapy on atherothrombotic stenosis

Background and Aims : Thrombus formation on a disrupted atherosclerotic plaque is a key event that leads to atherothrombosis. The aim of this study was to generate a hamster model of abdominal aorta atherothrombotic stenosis with morphological similarities to the human disease and the subsequent assessment of the reliability of B- mode ultrasound- guided laser photomechanical thrombolytic therapy accompanied by warfarin administration in this model.

Bindarit encapsulated nanoparticles prevent venous neointimal hyperplasia and restenosis in a murine angioplasty model

Monocyte and macrophage recruitment occur to the injured vessel wall after percutaneous transluminal angioplasty (PTA) of stenotic arteriovenous fistulas (AVF) through increased expression of MCP-1 leading to venous neointimal hyperplasia (VNH) and venous stenosis (VS). We hypothesized that adventitial delivery of Bindarit, an oral selective inhibitor of MCP-1, -2, and -3 encapsulated in poly lactic-co-glycolic acid (PLGA) nanoparticles embedded in a thermosensitive Pluronic F127 hydrogel (BN NP) could prevent VNH/VS formation in a murine model of PTA with AVF. Scanning electron microscope and dynamic light scattering were used to characterize the BN NP and control nanoparticles (NP C). Liquid chromatography with tandem mass spectrometry (LC-MS/MS) was used to study drug release kinetics. Immediately after PTA, in a murine model of AVF stenosis, BN NP or NP C was administrated to the adventitia of outflow veins. Animals were sacrificed 3 and 21 days later for gene expression, histomorphometric, and immunohistochemical analyses. Doppler ultrasound was performed weekly. There was no difference in the size and storage modulus of BN NP compared to controls. The pharmacokinetic analysis demonstrated increased drug release from BN NP when compared to controls. BN NP-treated vessels had reduced MCP-1, MCP-2, and MCP-3 gene, and protein levels, reduced macrophage/monocyte abundance, proinflammatory cytokines, and venous fibrosis resulting in positive vascular remodeling and improved patency with reduced VNH/VS. There was increased peak velocity 21 days after PTA in the BN NP group. Adventitial administration of BN NP to the outflow vein after PTA results in decreased VNH/VS.

Neutrophil extracellular traps participate in the development of cancer-associated thrombosis in patients with gastric cancer.

BACKGROUNDThe development of venous thromboembolism (VTE) is associated with high mortality among gastric cancer (GC) patients. Neutrophil extracellular traps (NETs) have been reported to correlate with the prothrombotic state in some diseases, but are rarely reported in GC patients.AIMTo investigate the effect of NETs on the development of cancer-associated thrombosis in GC patients.METHODSThe levels of NETs in blood and tissue samples of patients were analyzed by ELISA, flow cytometry, and immunofluorescence staining. NET generation and hypercoagulation of platelets and endothelial cells (ECs) in vitro were observed by immunofluorescence staining. NET procoagulant activity (PCA) was determined by fibrin formation and thrombin–antithrombin complex (TAT) assays. Thrombosis in vivo was measured in a murine model induced by flow stenosis in the inferior vena cava (IVC).RESULTSNETs were likely to form in blood and tissue samples of GC patients compared with healthy individuals. In vitro studies showed that GC cells and their conditioned medium, but not gastric mucosal epithelial cells, stimulated NET release from neutrophils. In addition, NETs induced a hypercoagulable state of platelets by upregulating the expression of phosphatidylserine and P-selectin on the cells. Furthermore, NETs stimulated the adhesion of normal platelets on glass surfaces. Similarly, NETs triggered the conversion of ECs to hypercoagulable phenotypes by downregulating the expression of their intercellular tight junctions but upregulating that of tissue factor. Treatment of normal platelets or ECs with NETs augmented the level of plasma fibrin formation and the TAT complex. In the models of IVC stenosis, tumor-bearing mice showed a stronger ability to form thrombi, and NETs abundantly accumulated in the thrombi of tumor-bearing mice compared with control mice. Notably, the combination of deoxyribonuclease I, activated protein C, and sivelestat markedly abolished the PCA of NETs.CONCLUSIONGC-induced NETs strongly increased the risk of VTE development both in vitro and in vivo. NETs are potential therapeutic targets in the prevention and treatment of VTE in GC patients.

Ruscogenin Alleviates Deep Venous Thrombosis and Pulmonary Embolism Induced by Inferior Vena Cava Stenosis Inhibiting MEK/ERK/Egr-1/TF Signaling Pathway in Mice.

Ruscogenin (RUS) has anti-inflammatory and antithrombotic effects, while its potential effects on deep venous thrombosis (DVT) and pulmonary embolism (PE) remain unclear. We aimed to elucidate the effects of RUS on DVT and PE induced by the inferior vena cava stenosis (IVCS) model and investigate the underlying mechanism. Male C57/BL6 mice were used to explore whether IVCS model could be complicated with deep venous thrombosis and pulmonary embolism. Then, effects of RUS on DVT and PE related inflammatory factors and coagulation were examined using H&E staining, ELISA, and real-time PCR. Western blot analysis was used to examine the effects of RUS on MEK/ERK/Egr-1/TF signaling pathway in PE. IVCS model induced DVT and complied with PE 48 h after surgery. Administration of RUS (0.01, 0.1, 1 mg/kg) inhibited DVT, decreased biomarker D-Dimer, cardiac troponin I, N-Terminal probrain natriuretic peptide in plasma to ameliorate PE induced by IVCS model. Meanwhile, RUS reduced tissue factor and fibrinogen content of lung tissue, inhibited P-selectin and C-reactive protein activity in plasma, and suppressed the expressions of interleukin-6 and interleukin-1β in mice. Furthermore, RUS suppressed the phosphorylation of ERK1/2 and MEK1/2, decreasing the expressions of Egr-1 and TF in the lung. IVCS model contributed to the development of DVT and PE in mice and was associated with increased inflammation. RUS showed therapeutic effects by inhibiting inflammation as well as suppressing the activation of MEK/ERK/Egr-1/TF signaling pathway.

A Novel Method to Determine the Cause of Left Internal Mammary Artery Instant Non-Patency Based on Transit Time Flow Measurement.

Objective: After coronary artery bypass grafting (CABG) surgery, the main causes of poor instant patency of left internal mammary arteries (LIMAs) are competitive flow and anastomotic stenosis, but how to determine the cause of LIMA non-patency without interfering with the native coronary artery is still a difficult problem to be solved urgently. Methods: In this study, a 0D-3D coupled multiscaled CABG model of anastomotic stenosis and competitive flow was constructed. After calculation, the flow waveform of the LIMA was extracted, and the waveform shape, common clinical parameters (average flow, PI, and DF), and graft flow FFT ratio results (F0/H1 and F0/H2) were analyzed. Results: For LIMA, these three common clinical parameters did not differ significantly between the anastomotic stenosis group and competitive flow group. However, the waveform shape and FFT ratio (especially F0/H2) of the competitive flow group were significantly different from those of the anastomotic stenosis group. When the cause was competitive flow, there was systolic backflow, and F0/H2 was too high (>14.89). When the cause was anastomotic stenosis, the waveform maintained a bimodal state and F0/H2 was in a normal state (about 1.17). Conclusion: When poor instant patency of the LIMA is found after CABG, the causes can be determined by graft flow waveform shape and F0/H2.

Molecular Detection of Venous Thrombosis in Mouse Models Using SPECT/CT.

The efficacy of thrombolysis is inversely correlated with thrombus age. During early thrombogenesis, activated factor XIII (FXIIIa) cross-links 2-AP to fibrin to protect it from early lysis. This was exploited to develop an 2-AP-based imaging agent to detect early clot formation likely susceptible to thrombolysis treatment. In this study, this imaging probe was improved and validated using In SPECT/CT in a mouse thrombosis model. In vitro fluorescent- and In-labelled imaging probe-to-fibrin cross-linking assays were performed. Thrombus formation was induced in C57Bl/6 mice by endothelial damage (FeCl) or by ligation (stenosis) of the infrarenal vena cava (IVC). Two or six hours post-surgery, mice were injected with In-DTPA-A16 and ExiTron Nano 12000, and binding of the imaging tracer to thrombi was assessed by SPECT/CT. Subsequently, ex vivo IVCs were subjected to autoradiography and histochemical analysis for platelets and fibrin. Efficient in vitro cross-linking of A16 imaging probe to fibrin was obtained. In vivo IVC thrombosis models yielded stable platelet-rich thrombi with FeCl and fibrin and red cell-rich thrombi with stenosis. In the stenosis model, clot formation in the vena cava corresponded with a SPECT hotspot using an A16 imaging probe as a molecular tracer. The fibrin-targeting A16 probe showed specific binding to mouse thrombi in in vitro assays and the in vivo DVT model. The use of specific and covalent fibrin-binding probes might enable the clinical non-invasive imaging of early and active thrombosis.

Establishment of two canine models of benign airway stenosis and the effect of mitomycin C on airway stenosis

ObjectivesCuffed endotracheal intubation and stent implantation were employed to simulate two types of benign airway stenosis and further to analysis the different features between them from trachecscopic characteristics, gross anatomy to histopathological changes. In addition, our study explored the therapeutic effect of mitomycin C at different concentrations on granulation tissue caused by stent implantation in order to provide a new therapeutic strategy for clinical treatment of benign airway stenosis. MethodsTwelve beagle dogs were randomly divided into four groups, with three dogs in each group. Group A: Three beagle dogs were intubated through oral trachea after general anesthesia and cuff pressure maintained at 200 mmHg for 24 h. Group B, Group C and Group D: endotracheal coated self-expanding metal stents were placed after general anesthesia under the guidance of bronchoscope. On the Day7 after stent implantation, Group B, as control group, was injected phosphate buffer solution of 1 ml into granulation tissue at the end of stent; Group C was injected mitomycin C of 1 ml at 0.4 mg/ml and Group D was injected mitomycin C of 1 ml at 0.8 mg/ml into granulation tissue at the end of metal airway stent respectively, the same method as Group B. Bronchoscopy was used to observe tracheal lumen on the seventh day, fourteenth day and twenty-first day after modeling and pathological changes were examined on twenty-first day. ResultsTwo models of benign airway stenosis can be established by cuffed endotracheal intubation and stent implantation. There was tracheal rupture in the trachea cartiage ring in the cuffed endotracheal intubation group, but was't in stent implantation group. Histopathological characteristics were different between cuffed endotracheal intubation and stent implantation groups. In stent placement groups, we found that the stenosis degree of mitomycin C at 0.4 mg/ml was approximately 19%–32%, mitomycin C at 0.8 mg/ml was approximately 16%–21% and the control group was approximately 36%–47%. ConclusionThe two models of canine benign tracheal stenosis induced by cuffed endotracheal intubation and stent implantation are relatively simple, reliable and reproducible and have different characteristics. Mitomycin C could inhibit proliferation of granulation tissue and attenuate the degree of airway stenosis caused by stent implantation.

Liraglutide alleviates vascular injury in diabetic rabbits with lower limb vascular stenosis through regulation of RCAN1.

The aim of the present study is to explore the possible mechanism that may have ameliorative effect of liraglutide (Lira) on diabetic lower extremity vascular stenosis. A diabetic rabbit model of lower extremity stenosis was established and treated with Lira. The intimal hyperplasia of the lower extremity and the oxidative stress level of vascular tissue were observed and examined. Vascular smooth muscle cells (VSMCs) induced by high glucose (HG) were treated with Lira, and RCAN1 overexpressing plasmid was constructed to transfect VCMCs. Lira treatment showed its association in significantly improving the hyperplasia of the intima, the level of oxidative stress, and the level of homeostasis model assessment of insulin resistance (HOMA-IR) in rabbits induced by diabetes and lower limb stenosis. In addition, Lira treatment reduced the elevated expression of RCAN1 in vascular tissues induced by diabetes. Not only could Lira treatment inhibit the increase of ROS level, proliferation and migration of VSMCs induced by HG, but reduce the expression of PCNA, MMP-9 and collagen I induced by HG. Overexpression of RCAN1 in VSMCs counteracted the effect of Lira, suggesting that Lira affected the proliferation and migration of VSMCs by regulating RCAN1. Our findings have important implications for Lira to exert beneficial outcomes in reducing excessive neointimal formation after lower extremity vascular injury in diabetic rabbits via the regulation of RCAN1.

Clinical, Histological, and Profibrotic Extracellular Matrix Protein Changes in a Model of Tracheal Stenosis Induced by Cervical Tracheal Autotransplantation

Background Tracheal stenosis (TS) is a complication of prolonged intubation, tracheotomy, and tracheal surgery that compromises the vascular supply. Animal models are essential for studying its pathophysiology and the effect of interventions. Objective To establish a TS model in rats secondary to tracheal autotransplantation with a graft submerged in bleomycin (Atx-Bleo). Additionally, to evaluate the clinical and histological changes, as well as the expression of newly formed collagen (NFC), isoforms of transforming growth factor beta (TGFβ), fibronectin (FN), elastin (ELN), integrin β1 (ITGβ1), and matrix metalloproteinase 1 (MMP1) in TS. Methods Twenty Wistar rats were divided into three groups: group I (n = 20) control; group II (n = 10) end-to-end anastomosis of the trachea (tracheoplasty); and group III (n = 10) Atx-Bleo. The animals were evaluated clinically, tomographically, macroscopically, morphometrically, and microscopically. NFC deposition, and the expression of profibrotic and antifibrotic proteins were evaluated in tracheal scars. Results All animals survived the surgical procedure and the study period. Compared with the other study groups, the Atx-Bleo group developed TS and fibrosis, exhibited higher expression of NFC, TGFβ1, TGFβ2, FN, ELN, and ITGβ1, and mild expression of TGFβ3 and MMP1 (p < 0.005; analysis of variance, Dunnett and Tukey tests). Conclusion Atx-Bleo in TS model rats produces tomographic and histological changes, and induces the upregulation of profibrotic proteins (TGFβ1, TGFβ2, collagen, FN, ELN, ITGβ1) and downregulation of antifibrotic proteins (TGFβ3, MMP1). Therefore, this model may be used to test new pharmacological treatments for reversing or preventing TS, and conduct basic studies regarding its pathophysiology.

Small Molecule Inhibitors of TBK1 Reduce Intimal Hyperplasia in a Model of Rat Carotid Artery Post-Balloon Angioplasty Stenosis

IFN-gamma is a recognized culprit of atherogenesis. Blockade of IFN-gamma signaling in vascular cells should positively impact intimal hyperplasia. Expression of STAT1, the key transcriptional regulator of IFN-gamma signaling, is regulated by autocrine IFN-beta. In turn, IFN-beta is downstream to the noncanonical I Kappa B kinase, TBK1. Our first aim was to validate, in vitro, the TBK1 inhibitor drug, amlexanox, and evaluate whether it reduces STAT1 expression, and thus, IFN-gamma signaling in vascular cells.

Numerical Simulations of Inlet and Outlet Air Flow Dynamics in Healthy and Stenotic Adult Airway

Most numerical studies of airflow resistance in the lungs have presented flow dynamics in different stenosis tracheobronchial airway generations. However, not much is known about the airflow characteristics in conditions where stenoses are present at both the airflow inlet and out letregions, especially in truncated tracheobronchial airway models. In this study, we constructed a healthy adult airway model and two stenosed airway models made up of generation six to nine (G6-G9). Computational Fluid Dynamics (CFD) simulations were performed in all airway models to investigate the airflow characteristics. We made comparison between the inlet and outlet air flow dynamics in the healthy and stenosis models during inspiration and expiration to understand if airflow resistance was higher in the upper or lower stenosis airway.Airflow velocity and wall shear stress were greater in the upper airway (G6) for both inspiration and expiration, while wall pressure was highest in the lower airway (G9). The airflow velocities in obstructed upper tracheobronchial airways during inspiration and expiration were about 3.84 m/ sand 1.49 m/s greater than in the lower airways during same respiratory cycle, respectively. The quantitative information in this study shows that stenosis at the lower airway generation has more effect on respiratory airflow than in the upper airway generations.

Fluid‐Structure Interaction Study of Coronary Artery Disease Biomechanics

Coronary artery disease (CAD) kills 1 in 7 in the United States. Atherosclerosis and thrombosis are both disease states that are impacted by biomechanical conditions in the blood vessels. Platelets and vascular endothelial cells are known to respond to their mechanical environments, which can be altered around a coronary stenosis. Certain pertinent mechanical parameters, such as vascular wall shear stress and strain, can be difficult or impossible to measure directly in vivo.Computational fluid dynamics (CFD) models and Fluid‐Structure Interaction (FSI) models are often used to assess coronary artery biomechanics. In this study, we developed three FSI models based on the computed tomography data from a patient: a normal model, a severe stenosis model with a 71% diameter occlusion (which would be a candidate for intervention), and a mild stenosis model (50% diameter occlusion, which would not be considered clinically severe). Our hypothesis was that the high‐resolution FSI model could reveal small changes in coronary biomechanics at the cellular level (microscopic scale), which may be used as a biomarker/indicator for endothelial cell and platelet activation at the early stage of disease development. FSI simulations were conducted in COMSOL Multiphysics. Time‐dependent velocity and pressure boundary conditions were applied at the inlet and outlet of the fluid domain, respectively. A five‐parameter Mooney‐Rivlin hyperelastic material model was used to model the material properties of the artery. A time‐dependent pressure boundary condition was applied to the outside of the vessel, mimicking squeezing of the cardiac muscle in areas of myocardial bridging. In the region of interest, a spatial resolution of less than 40 µm was achieved. This is comparable to the size of vascular endothelial cells (which can range in size from 20‐100 µm), allowing us to capture hemodynamic and solid mechanical behavior at the cellular level. In the normal geometry, wall shear stress (WSS) values peaked at 1.51 Pa. In the 71% stenosis throat, transient WSS could reach 200 Pa, while in the 50% stenosis throat, the maximum WSS was less than 5 Pa. In the recirculation zone of the 71% stenosis, WSS peaked at 4.66 Pa, while in the recirculation zone of the 50% stenosis WSS reduced to 0.83 Pa, which is pathologically low. Time‐averaged wall shear stress (TAWSS) was 0.62+0.002 Pa (average + standard error) in the normal model, 1.60+0.004 Pa in the 50% stenosis model, and 7.47+0.017 Pa in the 71% stenosis model. Time‐averaged wall shear stress gradient (TAWSSG) was 0.018+6.25*10‐5 N/m in the normal model, 0.150+3.4*10‐4 N/m in the 50% stenosis model, and 0.970+0.002 N/m in the 71% stenosis model. Radial strain in the normal, 71% stenosis throat, 50% stenosis throat, 71% recirculation zone, and 50% recirculation zone peaked at 7.5%, 4.0%, 6.3%, 0.5%, and 5.1% respectively, and the circumferential strain peaked at 8.9%, 4.4%, 6.6%, 0.6%, and 4.2% respectively. In summary, we were able to develop mesoscopic FSI models that can provide microscopic hemodynamic information at the cellular level. Such information can be used in the in vitro models to study biomechanical pathways associated with coronary artery atherosclerosis and thrombosis; it may also be used as biomarkers at the early stage of atherosclerosis development.

Computational fluid dynamic analysis of the nasal respiratory function before and after postero-superior repositioning of the maxilla.

Morphological changes in the upper airway and the resulting alteration in the nasal respiratory function after jawbone repositioning during orthognathic surgery have garnered attention recently. In particular, nasopharyngeal stenosis, because of the complex influence of both jaws, the effects of which have not yet been clarified owing to postero-superior repositioning of the maxilla, may significantly impact sleep and respiratory function, necessitating further functional evaluation. This study aimed to perform a functional evaluation of the effects of surgery involving maxillary repositioning, which may result in a larger airway resistance if the stenosis worsens the respiratory function, using CFD for treatment planning. A model was developed from CT images obtained preoperatively (PRE) and postoperatively (POST) in females (n = 3) who underwent maxillary postero-superior repositioning using Mimics and ICEM CFD. Simultaneously, a model of stenosis (STENOSIS) was developed by adjusting the severity of stenosis around the PNS to simulate greater repositioning than that in the POST. Inhalation at rest and atmospheric pressure were simulated in each model using Fluent, whereas pressure drop (ΔP) was evaluated using CFD Post. In this study, ΔP was proportional to airway resistance because the flow rate was constant. Therefore, the magnitude of ΔP was evaluated as the level of airway resistance. The ΔP in the airway was lower in the POST compared to the PRE, indicating that the analysis of the effects of repositioning on nasal ventilation showed that current surgery is appropriate with respect to functionality, as it does not compromise respiratory function. The rate of change in the cross-sectional area of the mass extending pharynx (α) was calculated as the ratio of each neighboring section. The closer the α-value is to 1, the smaller the ΔP, so ideally the airway should be constant. This study identified airway shapes that are favorable from the perspective of fluid dynamics.

Computational modeling and simulation of stenosis of the cerebral aqueduct due to brain tumor

ABSTRACT Stenosis of the cerebral aqueduct (CA) is featured in many studies relating to elevated intracranial cerebral pressures. It also presents a challenging situation to clinicians. Compressive forces play a lead role in pathological situations such as the presence of tumors and hence can cause obstruction to the flow of cerebrospinal fluid (CSF). Because of this barrier, excessive retention of CSF in the ventricles can occur. This, in turn, can contribute to increased pressure gradients inside the cranium. Most of the numerical models in the literature are restricted to modeling the CSF flow by considering the ventricle walls as rigid material, although in reality they are deformable. This paper, therefore, addresses the same from a holistic perspective by taking into consideration the dynamics of the flexible characteristics of the ventricular wall. It adds novelty to this field by reconstructing anatomically realistic ventricular wall behavior. To do this, the authors aim to develop a computational model of stenosis of the CA due to a brain tumor by invoking a fluid–structure interaction (FSI) method. The proposed three-dimensional FSI model is simulated under two cases: first, simulation of the pre-stenosis case with no interaction of tumor forces and, secondly, a stenosis condition with dynamic interaction of tumor forces. Comparison of the forces with and without a tumor reveals a marked obstruction of CSF outflow after the third ventricle and CA. In addition, a drastic rise in CSF velocity from 21.2 mm/s in the pre-stenosis case to 54.1 mm/s in the stenosis case is observed, along with a net increase in deformation of 0.144 mm on the walls of the ventricle. This paper makes a significant contribution to brain simulation studies for pressure calculations, in which the presence of tumors is a major concern.