In Vitro Characterization of Bicuspid Aortic Valve Hemodynamics Using Particle Image Velocimetry

The congenital bicuspid aortic valve (BAV) is associated with increased leaflet calcification, ascending aortic dilatation, aortic stenosis (AS) and regurgitation (AR). Although underlying genetic factors have been primarily implicated for these complications, the altered mechanical environment of BAVs could potentially accelerate these pathologies. The objective of the current study is to characterize BAV hemodynamics in an in vitro system. Two BAV models of varying stenosis and jet eccentricity and a trileaflet AV (TAV) were constructed from excised porcine AVs. Particle Image Velocimetry (PIV) experiments were conducted at physiological flow and pressure conditions to characterize fluid velocity fields in the aorta and sinus regions, and ensemble averaged Reynolds shear stress and 2D turbulent kinetic energy were calculated for all models. The dynamics of the BAV and TAV models matched the characteristics of these valves which are observed clinically. The eccentric and stenotic BAV showed the strongest systolic jet (V = 4.2 m/s), which impinged on the aortic wall on the non-fused leaflet side, causing a strong vortex in the non-fused leaflet sinus. The magnitudes of TKE and Reynolds stresses in both BAV models were almost twice as large as comparable values for TAV, and these maximum values were primarily concentrated around the central jet through the valve orifice. The in vitro model described here enables detailed characterization of BAV flow characteristics, which is currently challenging in clinical practice. This model can prove to be useful in studying the effects of altered BAV geometry on fluid dynamics in the valve and ascending aorta. These altered flows can be potentially linked to increased calcific responses from the valve endothelium in stenotic and eccentric BAVs, independent of concomitant genetic factors.     

Simulation of Self Expanding Transcatheter Aortic Valve in a Realistic Aortic Root: Implications of Deployment Geometry on Leaflet Deformation

Self expanding Transcatheter Aortic Valve Replacements (TAVR) can conform to the geometry of the aortic annulus and the calcified leaflet complex, which may result in leaflet distortion and altered leaflet kinematics, but such changes have not yet been characterized. In this study we developed a computational model to investigate the deployment of a self expanding TAVR in a realistic aortic root model derived from multi-slice computed tomography (MSCT) images. We simulated TAVR crimping/deployment in realistic and idealized aortic root models, followed by diastolic loading of the TAVR leaflets in its final deployed configuration. The TAVR deployed in a realistic aortic root had increased peak loading in the commissural region of the leaflets compared to TAVRs under idealized circular deployment conditions (2.97 vs. 1.52 MPa). Furthermore, orientation of the TAVR in the asymmetric aortic annulus such that the commissures of the TAVR are aligned with the native valve commissures minimized the effect of TAVR stent distortion on peak stresses in the TAVR leaflets (2.97 vs. 2.35 MPa). We propose that preoperative planning of the orientation of the TAVR in the aortic root annulus might minimize the impact of potential stent distortion on leaflet function and may in turn increase long term leaflet durability.     

On the Mechanics of Transcatheter Aortic Valve Replacement

Transcatheter aortic valves (TAVs) represent the latest advances in prosthetic heart valve technology. TAVs are truly transformational as they bring the benefit of heart valve replacement to patients that would otherwise not be operated on. Nevertheless, like any new device technology, the high expectations are dampened with growing concerns arising from frequent complications that develop in patients, indicating that the technology is far from being mature. Some of the most common complications that plague current TAV devices include malpositioning, crimp-induced leaflet damage, paravalvular leak, thrombosis, conduction abnormalities and prosthesis-patient mismatch. In this article, we provide an in-depth review of the current state-of-the-art pertaining the mechanics of TAVs while highlighting various studies guiding clinicians, regulatory agencies, and next-generation device designers.     

人工心瓣在脉动循环模拟系统上的能量损耗的研究

本文对常用的不同尺寸的５种人工心瓣在脉循环系统的主动脉瓣位，在不同的心率，心输邮量和主动脉平均压下进行能量损耗（Ｅｎｅｒｇｙｌｏｓｓｅｓ）的评价。人工心瓣的能量损耗据所计录的左心室压，主动脉压，前反向的跨瓣流量而计算。结果表明，跨瓣压关（ΔＰ）主输量（ＣＯ）的增加而增加，随心率（ＨＲ）和心瓣尺寸（ＶＳ）的增加而减小；跨瓣反流量（Ｒｅｇ）随ＶＳ的增加而增加，且除笼球瓣外，Ｒｅｇ随ＣＯ的增加而减少；主     

体外模拟心血管系统血液动力学性能分析

为研究人工心脏和心血管系统之间的血液动力学作用机制．根据弹性腔模型建立了一套能反映血液动力学特性的体外血液循环模拟实验装置，测试血液动力学参量与心室后负荷（即外周力R和动脉顺应性C）以及每搏心输出量Vs，心动周期T和心室收缩时间间隔Ts，前负荷等六个参量之间的相互关系．通过改变六个参量中的某一个参量而固定其余参量，测试这个参量对动脉血压及流量的影响情况。实验结果与生理情况和数学模型分析相符合。压力和流量波呈脉动性，与真实生理波形相似。整个模拟装置能够反映血液动力学特性。     

微血管网血流动力学的体外模拟系统

目的 :研究不同微血管网内血流动力学的特点。方法 :自行设计制做的体外循环模拟系统 ,由搏动泵、阻尼器、液容器 (Windkessel腔 )及各种不同口径的弹性管组成。根据不同器官微血管特点 ,用不同口径的弹性管制作了发夹状、树枝状及网囊状的微血管模型。用3个参数 (心率、收缩压Ps/舒张压Pd、动脉血管顺应性C)表示模拟循环系统的动力学状态 ,在此基础上对三种微血管模型在不同的循环压状态下 ,进行了血流动力学模拟研究。结果 :经检验该循环系统在循环回路上模拟的压力及脉动波形基本符合心血管循环的生理特点。当循环压改变时 ,发夹状微血管的第一排管袢内流量和压力的变化较第三排略大 ;当循环压降低时 ,树枝状微血管的终末分支毛细管内压力减少幅度大于初级分支 ,当循环压增高时 ,终末分支毛细管内压力增加幅度小于初级分支 ;网囊状微血管在微循环压降低时其顶端毛细管的压力减少幅度最大。其结果与生理研究相吻合。结论 :本模型在模拟微血管血流动力学方面 ,有较好的仿真性和实用性 ,与活体研究相结合 ,可完善微循环的基础研究。     

Clinical Outcomes of Transcatheter Aortic Valve Implantation for Native Aortic Valves in Patients with Low Coronary Heights

PurposeAcute coronary occlusion is a rare but fatal complication that may occur during trans-catheter aortic valve implantation (TAVI) and appears more frequently in patients with low coronary heights. We evaluated the feasibility of self-expanding valves in patients with low coronary heights undergoing TAVI.Materials and MethodsTAVI for native aortic valve stenosis was conducted in 276 consecutive patients between 2015 and 2019 at our institute. Using multi-detector computed tomography (MDCT), information on the aortic valve, coronary arteries, and vascular anatomy in 269 patients was analyzed. Patients with low coronary heights were defined as those with coronary heights of 10 mm or less during MDCT analysis.ResultsAmong the 269 patients, 29 (10.8%) patients had coronary arteries with low heights. The mean coronary height was 8.9±1.2 mm in the left coronary artery. These patients with low coronary heights were treated with self-expandable (n=28) or balloon-expandable (n=1) valves. Prophylactic coronary protection with a guidewire, balloon, or stent prepositioned down at-risk coronary arteries was not pursued in all patients. No acute coronary occlusion occurred in any of these patients during TAVI. Five patients (17.9%) died during follow-up (average of 553.8 days), including four from non-cardiogenic causes and one from a cardiogenic (aggravation of heart failure) cause.ConclusionA considerable number of patients with low coronary heights were observed among TAVI candidates in this study. Use of a self-expandable valve may be feasible for successful TAVI without acute coronary occlusion in patients with low coronary heights.     

Ultrastructural and Spectrophotometric Study on the Effects of Putative Triggers on Aortic Valve Interstitial Cells in In Vitro Models Simulating Metastatic Calcification

Metastatic calcification of cardiac valves is a common complication in patients affected by chronic renal failure. In this study, primary bovine aortic valve interstitial cells (AVICs) were subjected to pro‐calcific treatments consisting in cell stimulation with (i) elevated inorganic phosphate (Pi = 3 mM), to simulate hyperphosphatemic conditions; (ii) bacterial endotoxin lipopolysaccharide (LPS), simulating direct effects by microbial agents; and (iii) conditioned media (CM) derived from cultures of either LPS‐stimulated heterogenic macrophages (commercial murine RAW264.7 cells) or LPS‐stimulated fresh allogenic monocytes/macrophages (bCM), simulating consequent inflammatory responses, alone or combined. Compared to control cultures, spectrophotometric assays revealed shared treatment‐dependent higher values of both calcium amounts and alkaline phosphatase activity for cultures involving the presence of elevated Pi. Ultrastructurally, shared peculiar pro‐calcific degeneration patterns were exhibited by AVICs from these latter cultures irrespectively of the additional treatments. Disappearance of all cytomembranes and concurrent formation of material showing positivity to Cuprolinic Blue and co‐localizing with silver precipitation were followed by the outcropping of such a material, which transformed in layers outlining the dead cells. Subsequent budding of these layers resulted in the formation of bubbling bodies and concentrically laminated calcospherulae mirroring those in actual soft tissue calcification. In conclusion, the in vitro models employed appear to be reliable tools for simulating metastatic calcification and indicate that hyperphosphatemic‐like conditions could trigger valve calcification per se, with LPS and allogenic macrophage‐derived secretory products acting as possible calcific enhancers via inflammatory responses. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.     

Influence of Vasoactive Drugs on Wall Shear Stress Distribution in the Abdominal Aortic Bifurcation: An In Vitro Study

The present study compares the wall shear stress (rate) distribution in a compliant aortic bifurcation model under three different hemodynamic states: normal state, angiotensin II infusion state (vasoconstrictor), and isoproterenol infusion state (vasodilator). Using a Newtonian blood analog fluid, flow wave forms corresponding to each flow state were generated in an in vitro flow loop and a photographic flow visualization technique was employed to measure wall shear rate. The results indicate a zone of low mean wall shear stress and highly oscillatory shear stress on the outer (lateral) wall of the bifurcation. In this zone, the mean wall shear stress became negative for all three hemodynamic states indicating flow separation. However, the spatial extent of the flow separation zone was not affected significantly by the flow state. The study also revealed a large spatial variation of the phase angle between the hoop strain (circumferential strain due to radial artery expansion) and the wall shear stress, the two main mechanical stimuli acting on endothelial cells which affect their biology. In the zone of low mean wall shear stress on the outer wall, the two stimuli were more out of phase relative to the mother branch, whereas they were less out of phase (by about 50°) on the inner wall (flow divider side). This phase angle was affected significantly by the flow state. For angiotensin II, the phase angle reached a maximum of 125° in the low mean shear zone while the maximum was 94° and 66° for the normal and isoproterenol states, respectively. Our observation that large phase angles between the hoop strain and wall shear stress wave forms are localized in the low shear stress region where atherosclerotic disease occurs suggests the possible physiological relevance of this phase angle to the development of atherosclerosis. © 1998 Biomedical Engineering Society. PAC98: 8745Hw     

Quantification of Biomechanical Interaction of Transcatheter Aortic Valve Stent Deployed in Porcine and Ovine Hearts

Success of the deployment and function in transcatheter aortic valve replacement is heavily reliant on the tissue–stent interaction. The present study quantified important tissue–stent contact variables of self-expanding transcatheter aortic valve stents when deployed into ovine and porcine aortic roots, such as the stent radial expansion force, stent pullout force, the annulus deformation response and the coefficient of friction on the tissue–stent contact interface. Braided Nitinol stents were developed, tested to determine stent crimped diameter vs. stent radial force from a stent crimp experiment, and deployed in vitro to quantify stent pullout, aortic annulus deformation, and the coefficient of friction between the stent and the aortic tissue from an aortic root–stent interaction experiment. The results indicated that when crimped at body temperature from 26 mm to 19, 21 and 23 mm stent radial forces were approximately 30–40% higher than those crimped at room temperature. Coefficients of friction leveled to approximately 0.10 ± 0.01 as stent wire diameter increased and annulus size decreased from 23 to 19 mm. Regardless of aortic annulus size and species tested, it appeared that a minimum of about 2.5 mm in annular dilatation, caused by about 60 N of radial force from stent expansion, was needed to anchor the stent against a pullout into the left ventricle. The study of the contact biomechanics in animal aortic tissues may help us better understand characteristics of tissue–stent interactions and quantify the baseline responses of non-calcified aortic tissues.     

起旋式人工主动脉瓣构型设计及血流动力学评价

目的 设计一种附起旋功能的双叶机械瓣,通过改善其血流状态预防术后并发症。 方法 基于导流片式局部起旋器结构,将瓣叶作为导流叶片,并定义瓣叶包角以探究具有较优血流动力学特性的瓣膜构型。 应用有限元分析软件,对心缩期峰值流量状态下的主动脉流场进行仿真,螺旋性、壁面切应力分布等血流动力学特征。 结果 相较于对照瓣膜,起旋瓣具有更大的有效开口面积与更小的跨瓣压差,一定瓣叶包角范围内的起旋瓣能促进右手螺旋流的生成,并使血流趋向流道中心;起旋瓣壁面切应力分布也更加均匀,具有较少的低应力区与高应力区,壁面切应力峰值也相对较小。 针对研究中的主动脉模型,具有最优血流动力学特性的瓣叶包角为 15° ~ 20°。 结论 该新型人工主动脉瓣能调节主动脉内的血流特征,降低主动脉瓣置换术引起主动脉扩张与主动脉瘤的风险,对未来机械瓣构型设计具有指导意义。     

Colorimetric In Vitro Evaluation of T-Cell Cytotoxicity

We propose a new colorimetric method for evaluation of specific T lymphocyte cytotoxicity based on the capacity of viable cells to incorporate alamar blue dye, an indicator of cell metabolic activity. This method is effective for highly specific strains of cytotoxic T lymphocytes and for primary T killers formed in vivo and constituting a small part of analyzed cell population. This test is a simple nonradioactive method for evaluating specific cellular cytotoxicity exhibiting sufficient sensitivity for evaluation of this parameter in the presence of effector cells.     

In Vitro Investigation of the Effect of Left Ventricular Assist Device Speed and Pulsatility Mode on Intraventricular Hemodynamics

Annals of Biomedical Engineering - Stroke has become the main cause of mortality and morbidity in patients treated with Left Ventricular Assist Devices (LVADs). The hemodynamics of the left...     

Impact of Human Adipose Tissue-Derived Stem Cells on Malignant Melanoma Cells in An In Vitro Co-culture Model

This study focuses on the interactions of human adipose tissue-derived stem cells (ADSCs) and malignant melanoma cells (MMCs) with regard to future cell-based skin therapies. The aim was to identify potential oncological risks as ADSCs could unintentionally be sited within the proximity of the tumor microenvironment of MMCs. An indirect co-culture model was used to analyze interactions between ADSCs and four different established melanoma cell lines (G-361, SK-Mel-5, MeWo and A2058) as well as two low-passage primary melanoma cell cultures (M1 and M2). Doubling time, migration and invasion, angiogenesis, quantitative real-time PCR of 229 tumor-associated genes and multiplex protein assays of 20 chemokines and growth factors and eight matrix metalloproteinases (MMPs) were evaluated. Co-culture with ADSCs significantly increased migration capacity of G-361, SK-Mel-5, A2058, MeWo and M1 and invasion capacity of G-361, SK-Mel-5 and A2058 melanoma cells. Furthermore, conditioned media from all ADSC-MMC-co-cultures induced tube formation in an angiogenesis assay in vitro. Gene expression analysis of ADSCs and MMCs, especially of low-passage melanoma cell cultures, revealed an increased expression of various genes with tumor-promoting activities, such as CXCL12, PTGS2, IL-6, and HGF upon ADSC-MMC-co-culture. In this context, a significant increase (up to 5,145-fold) in the expression of numerous tumor-associated proteins could be observed, e.g. several pro-angiogenic factors, such as VEGF, IL-8, and CCL2, as well as different matrix metalloproteinases, especially MMP-2. In conclusion, the current report clearly demonstrates that a bi-directional crosstalk between ADSCs and melanoma cells can enhance different malignant properties of melanoma cells in vitro.