叉头框-c2基因在主动脉弓发育过程中的作用

为了研究叉头框-c2（Forkhead Box c2, Fox c2）基因在心血管发生和发育中的作用, 通过制作小鼠的Fox c2 基因无效突变,解析该基因缺失鼠主动脉弓的异常发育状况.纯合子胎鼠从12.5天胚胎(embryo, E)开始有宫内死亡;即使完成宫内发育过程,新生鼠出生24 h后也全部死亡.这些鼠全部表现出与人的先天性心血管发育缺陷相似的B型或C型主动脉弓离断.杂合子鼠发育正常.E10.5胚胎的原位杂交分析显示,Fox c2 mRNA在第三、第四和第六弓型动脉强烈表达,而第四弓型动脉在E10.5胚胎后逐渐消失.这些结果表明,在主动脉弓形成过程中,Fox c2基因产物是左第四弓形动脉广泛改建所必需.     

小鼠主动脉弓缩窄模型的建立及评价

目的通过显微外科技术建立小鼠主动脉弓缩窄压力超负荷模型,探讨心脏形态及功能变化的规律。方法135只雄性昆明小鼠随机分为主动脉弓缩窄组75只和假手术组60只。在术前、术后1周、4周、6周、8周1、2周进行高频心脏超声、血流动力学、心脏病理学检测,并对器官称重,对死亡原因进行分析。结果（1）主动脉弓缩窄手术成功率为88%;（2）与假手术组比较,术后4周,缩窄组小鼠出现左室向心性肥厚,左心室收缩期、舒张期后壁厚度（Pwsth;Pwdth）、左心室重量指数（LVMI）显著增加（P〈0.05）,术后6、8、12周上述指标呈轻度上升趋势;术后4、68、、12周,缩窄组小鼠动脉收缩压（SBP）、动脉舒张压（DBP）、左心室收缩压（LVSP）、左心室舒张末压（LVEDP）显著增加（P〈0.05）;术后8周,缩窄组小鼠表现为离心性肥厚,左心室收缩末期、舒张末期内径（LVESd;LVEDd）显著增加（P〈0.05）;术后12周,缩窄组小鼠出现失代偿性心力衰竭,左心室射血分数（EF%）、左心室压力上升和下降最大速率（dp/dtmax;dp/dtmin）显著降低（P〈0.05）,与8周缩窄组比较,12周缩窄组SBP、DBP、LVSP、LVEDP显著降低（P〈0.05）。结论通过主动脉弓缩窄,可以建立稳定的小鼠压力超负荷诱导左室向心性肥厚致心衰的动物模型,类似人类心肌肥厚向心衰发展的病理过程,是用于临床研究的一种较理想动物模型。     

Fluid-Structure Interaction Analysis of Pulsatile Flow within a Layered and Stenotic Aorta

In this paper, the hemodynamic characteristics of blood flow and stress distribution in a layered and stenotic aorta are investigated. By introducing symmetrical and unsymmetrical stenosis, the influence of stenosis morphology and stenotic ratio on the coupled dynamic responses of aorta is clarified. In the analysis, the in-vivo pulsatile waveforms and fully fluid–structure interaction (FSI) between the layered elastic aorta and the blood are considered. The results show that the fluid domain is abnormal in the stenotic aorta, and the whirlpool forms at the obstructed and downstream unobstructed regions. The maximum wall shear stresses appear at the throat of the stenosis. Downstream region appears low and oscillated shear stresses. In addition, along with the increase of the stenotic ratio, the amplitude of the maximum shear stress will be intensively increased and localized, and the sensitivity is also increased. In the aorta with unsymmetrical stenosis, the Von Mises stresses reach the peak value at the side with the surface protuberance, but they are reduced at the side with no protuberance. The sign variation of the layer interface shear stresses near the throat indicates the variation of the shear direction which increases the opportunity of shear damage at the transition plane. Moreover, the shear stress levels at the fluid-solid and intima-media interfaces are higher than that at the media-adventitia interface. The unsymmetrical stenosis causes higher stresses at the side with the surface protuberance than symmetrical one, but lower at the side with no protuberance. These results provide an insight in the influence of the stenosis, as well as its morphology, on the pathogenesis and pathological evolution of some diseases, such as arteriosclerosis and aortic dissection.     

OSAHS患者上气道和软腭的流固耦合有限元模型的建立

目的:重建OSAHS患者上气道和软腭的流固耦合有限元模型,研究OSAHS患者上气道及软腭气流动力学特征,为进一步探讨OSAHS的的发病机制奠定基础。方法:对一名中度OSAHS患者的上气道及周围组织进行MRI扫描,将以DICOM格式存储的扫描数据导入Mimics15.0软件中进行预处理,得到上气道和软腭的模型;再利用逆向工程软件Geomagic Studio 2013建立了2 mm气道壁;然后在3-D重建软件NX中,生成气道壁和气道以及软腭之间的组合模型;最后将该组合模型导入ANSYS Workbench13.0软件中,通过网格划分、定义材料属性、设定模型的边界条件操作建立了上气道和软腭的流固耦合有限元模型。结果:利用Mimics、Ansys等软件建立了完整的上气道和软腭的流固耦合有限元模型。共得到气道:2806835单元和529281个节点;气道壁:2304348单元和3487609个节点;软腭:131855单元和204784个节点。结论:本研究建立的上气道及软腭的流固耦合有限元模型符合人体的生物力学特点,为下一步的数值模拟实验提供了一个更真实、可靠的模型。     

Fluid-structure interaction modeling of aneurysmal arteries under steady-state and pulsatile blood flow: a stability analysis

Tortuous aneurysmal arteries are often associated with a higher risk of rupture but the mechanism remains unclear. The goal of this study was to analyze the buckling and post-buckling behaviors of aneurysmal arteries under pulsatile flow. To accomplish this goal, we analyzed the buckling behavior of model carotid and abdominal aorta with aneurysms by utilizing fluid-structure interaction (FSI) method with realistic waveforms boundary conditions. FSI simulations were done under steady-state and pulsatile flow for normal (1.5) and reduced (1.3) axial stretch ratios to investigate the influence of aneurysm, pulsatile lumen pressure and axial tension on stability. Our results indicated that aneurysmal artery buckled at the critical buckling pressure and its deflection nonlinearly increased with increasing lumen pressure. Buckling elevates the peak stress (up to 118%). The maximum aneurysm wall stress at pulsatile FSI flow was (29%) higher than under static pressure at the peak lumen pressure of 130 mmHg. Buckling results show an increase in lumen shear stress at the inner side of the maximum deflection. Vortex flow was dramatically enlarged with increasing lumen pressure and artery diameter. Aneurysmal arteries are more susceptible than normal arteries to mechanical instability which causes high stresses in the aneurysm wall that could lead to aneurysm rupture.     

Three-Dimensional Computational Modeling of an Extra-Descending Aortic Assist Device Using Fluid-Structure Interaction

BackgroundThe incidence of heart failure is anticipated to rise by 2030, resulting in more than 8 million adults with this condition in US. Despite the advancement in pharmacological and surgical treatments, some patients progress to severe forms of cardiac dysfunction requiring cardiac transplantation as a last-resort treatment. Cardiac assist devices play an essential role in the recovery of normal cardiac performance through reversible remodeling or in assisting the weak organ to prolong survival rate. However, these devices need to be monitored carefully, as prolonged use may lead to physiological maladaptation and further cardiac complications. The optimization of such devices has done through the development and use of numerical simulations that allow the analysis of in-vivo hemodynamic patterns of blood flow. This study aims to investigate the performance of a model of extra-aortic assist device surrounding the descending aorta through three-dimensional patient-specific modeling.MethodsA three-dimensional model of the aorta was constructed from patient-specific cardiac CT images of a 60-year-old male diagnosed with left ventricular failure at the Tehran Heart Center (THC). Numerical simulation was conducted for two complete cardiac cycles using fluid-structure interaction (FSI) analysis under the assumption that the balloon and the aortic vessel behave as linear elastic materials, and that blood is a Newtonian and incompressible fluid.ResultsThe numerical simulation demonstrated a high correlation between the FSI analysis and clinical data of the patient-specific anatomical and physiological conditions. Blood velocity, pressure, deformation, and strain contours were simulated and analyzed through three-dimensional modeling. Compared to the unassisted aorta, the device provided an increase in blood flow displacement of an additional 15 ml of blood in the descending aorta, brachiocephalic, carotid, and subclavian arteries. The maximum von Mises stress distribution across the aortic vessel was higher than the stress imposed on the system in the unassisted heart, with values of 3.3 MPa and 0.28 MPa, respectively. Numerical investigation of structural responses revealed that no remarkable force was exerted on the aortic valve by the device at the descending aorta.ConclusionWe present the numerical investigation of a counterpulsation device around the descending aorta that has not previously been tested on human or animal models. While this extra-aortic balloon pump (EABP) did not show a significant improvement in coronary perfusion, there is room for improvement in further studies to optimize the geometry of the balloon. Additional investigations are required to determine the efficacy of this device and its safety before in-vivo experimental studies are pursued. This simulation has clinical relevance when choosing an appropriate cardiac assist device to address patient-specific physiological and pathological conditions.     

3D Fluid-Structure Interaction Canine Heart Model with Patch to Quantify Mechanical Conditions for Optimal Myocardium Stem Cell Growth and Tissue Regeneration

Right ventricular (RV) dysfunction is a common cause of heart failure in patients with congenital heart defects and often leads to impaired functional capacity and premature death. Myocardial tissue regeneration techniques are being developed for the potential that viable myocardium may be regenerated to replace scar tissues in the heart or used as patch material in heart surgery. 3D computational RV/LV/Patch models with fluid-structure interactions (FSI) were constructed based on data from a healthy dog heart to obtain local fluid dynamics and structural stress/strain information and identify optimal conditions under which tissue regeneration techniques could achieve best outcome. RV/LV/Patch geometry and blood pressure data were obtained from a dog following established procedures. Four FSI models were used to quantify the influence of different patch materials (Dacron scaffold, treated pericardium) on local environment around the patch area, especially focusing on the thickness and stiffness of the patch. Our results indicated that changes in patch stiffness had little impact on the ejection fraction of the right ventricle because the total patch area was small. However, patch stiffness had huge impact on local RV maximum principal stress (Stress-P1) and strain (Strain-P1) around the patch area. Compared to the no-patch model, patch models had increased Stress-P1 and decreased Strain-P1 values in the patch area. Softer patches were associated with greater stress/strain variations. Thinner patch led to complex local flow environment which may have impact on myocytes seeding and RV remodeling. Our multi-physics RV/LV/Patch FSI model can serve as a useful tool to investigate cellular biology and tissue regeneration under localized flow and structural stress environment.     

Aortic valve leaflet wall shear stress characterization revisited: impact of coronary flow

Computational characterizations of aortic valve hemodynamics have typically discarded the effects of coronary flow. The objective of this study was to complement our previous fluid–structure interaction aortic valve model with a physiologic coronary circulation model to quantify the impact of coronary flow on aortic sinus hemodynamics and leaflet wall shear stress (WSS). Coronary flow suppressed vortex development in the two coronary sinuses and altered WSS magnitude and directionality on the three leaflets, with the most substantial differences occurring in the belly and tip regions.     

Direct numerical simulation of a 2D-stented aortic heart valve at physiological flow rates

We study the nonlinear interaction of an aortic heart valve, composed of hyperelastic corrugated leaflets of finite density attached to a stented vessel under physiological flow conditions. In our numerical simulations, we use a 2D idealised representation of this arrangement. Blood flow is caused by a time-varying pressure gradient that mimics that of the aortic valve and corresponds to a peak Reynolds number equal to 4050. Here, we fully account for the shear-thinning behaviour of the blood and large deformations and contact between the leaflets by solving the momentum and mass balances for blood and leaflets. The mixed finite element/Galerkin method along with linear discontinuous Lagrange multipliers for coupling the fluid and elastic domains is adopted. Moreover, a series of challenging numerical issues such as the finite length of the computational domain and the conditions that should be imposed on its inflow/outflow boundaries, the accurate time integration of the parabolic and hyperbolic momentum equations, the contact between the leaflets and the non-conforming mesh refinement in part of the domain are successfully resolved. Calculations for the velocity and the shear stress fields of the blood reveal that boundary layers appear on both sides of a leaflet. The one along the ventricular side transfers blood with high momentum from the core region of the vessel to the annulus or the sinusoidal expansion, causing the continuous development of flow instabilities. At peak systole, vortices are convected in the flow direction along the annulus of the vessel, whereas during the closure stage of the valve, an extremely large vortex develops in each half of the flow domain.     

Estimation of the physiological mechanical conditioning in vascular tissue engineering by a predictive fluid-structure interaction approach

The in vitro replication of physiological mechanical conditioning through bioreactors plays a crucial role in the development of functional Small-Caliber Tissue-Engineered Blood Vessels. An in silico scaffold-specific model under pulsatile perfusion provided by a bioreactor was implemented using a fluid-structure interaction (FSI) approach for viscoelastic tubular scaffolds (e.g. decellularized swine arteries, DSA). Results of working pressures, circumferential deformations, and wall shear stress on DSA fell within the desired physiological range and indicated the ability of this model to correctly predict the mechanical conditioning acting on the cells-scaffold system. Consequently, the FSI model allowed us to a priori define the stimulation pattern, driving in vitro physiological maturation of scaffolds, especially with viscoelastic properties.     

Pollen Tubes: a Model System for Plant Cell Growth*

Recent observations of pollen tubes show that these tubes may grow in a pulsatory fashion (Pierson et al., 1995; Plyushch et al., 1995; Li et al., 1996; Geitmann et al., 1996a, 1996b), in which phases of fast and slow growth alternate regularly. The occurrence of pulsatory growth has been used by Geitmann and coworkers (1996b) to study factors that might control growth. Their results emphasize the role of the cell wall and secretory events in regulating pollen tube growth. Here we will briefly review recent results related to the role of exocytosis, cytoskeleton, calcium and the cell wall in pollen tube growth.     

Porphyromonas gingivalis as a Model Organism for Assessing Interaction of Anaerobic Bacteria with Host Cells

Anaerobic bacteria far outnumber aerobes in many human niches such as the gut, mouth, and vagina. Furthermore, anaerobic infections are common and frequently of indigenous origin. The ability of some anaerobic pathogens to invade human cells gives them adaptive measures to escape innate immunity as well as to modulate host cell behavior. However, ensuring that the anaerobic bacteria are live during experimental investigation of the events may pose challenges. Porphyromonas gingivalis, a Gram-negative anaerobe, is capable of invading a variety of eukaryotic non-phagocytic cells. This article outlines how to successfully culture and assess the ability of P. gingivalis to invade human umbilical vein endothelial cells (HUVECs). Two protocols were developed: one to measure bacteria that can successfully invade and survive within the host, and the other to visualize bacteria interacting with host cells. These techniques necessitate the use of an anaerobic chamber to supply P. gingivalis with an anaerobic environment for optimal growth.The first protocol is based on the antibiotic protection assay, which is largely used to study the invasion of host cells by bacteria. However, the antibiotic protection assay is limited; only intracellular bacteria that are culturable following antibiotic treatment and host cell lysis are measured. To assess all bacteria interacting with host cells, both live and dead, we developed a protocol that uses fluorescent microscopy to examine host-pathogen interaction. Bacteria are fluorescently labeled with 2'',7''-Bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein acetoxymethyl ester (BCECF-AM) and used to infect eukaryotic cells under anaerobic conditions. Following fixing with paraformaldehyde and permeabilization with 0.2% Triton X-100, host cells are labeled with TRITC phalloidin and DAPI to label the cell cytoskeleton and nucleus, respectively. Multiple images taken at different focal points (Z-stack) are obtained for temporal-spatial visualization of bacteria. Methods used in this study can be applied to any cultivable anaerobe and any eukaryotic cell type.