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1.

Aortic stenosis is a common cardiac condition that impacts the aorta’s hemodynamics downstream of the affected valve. We sought to better understand how non-uniform stiffening of a stenotic aortic valve would affect the wall shear stress (WSS) experienced by the walls of the aorta and the residence time near the valve. Several experimental configurations were created by individually stiffening leaflets of a polymer aortic valve. These configurations were mounted inside an in vitro experimental setup. Digital particle image velocimetry (DPIV) was used to measure velocity profiles inside a model aorta. The DPIV results were used to estimate the WSS and residence time. Our analysis suggests that leaflet asymmetry greatly affects the amount of WSS by vectoring the systolic jet and stiffened leaflets have an increased residence time. This study indicates that valve leaflets with different stiffness conditions can have a more significant impact on wall shear stress than stenosis caused by the uniform increase in all three leaflets (and the subsequent increased systolic velocity) alone. This finding is promising for creating customizable (patient-specific) prosthetic heart valves tailored to individual patients.

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2.
An understanding of how mechanical forces impact cells within valve leaflets would greatly benefit the development of a tissue-engineered heart valve. In this study, the effect of constant ambient pressure on the biological properties of heart valve leaflets was evaluated using a custom-designed pressure system. Native porcine aortic valve leaflets were exposed to static pressures of 100, 140, or 170 mmHg for 48 h. Collagen synthesis, DNA synthesis, sulfated glycoaminoglycan (sGAG) synthesis, alpha-SMC actin expression, and extracellular matrix (ECM) structure were examined. Results showed that elevated pressure caused an increase in collagen synthesis. This increase was not statistically significant at 100 mmHg, but at 140 mmHg and 170 mmHg collagen synthesis increased by 37.5 and 90%, respectively. No significant difference in DNA or sGAG synthesis was observed at elevated pressures, with the exception that DNA synthesis at 100 mmHg decreased. A notable decline in alpha-SMC actin was observed over the course of the experiments although no significant difference was observed between the pressure and control groups. It was concluded that elevated pressure caused a proportional increase in collagen synthesis of porcine aortic valve leaflets, but was unable to preserve alpha-SMC actin immunoreactive cells.  相似文献   

3.
The effects of the outflow of aortic blood through the celiac and renal arteries on the flow field in the external iliac arteries were studied under steady and physiologically realistic pulsatile flow conditions. Laser Doppler velocimetry (LDV) measurements were made close to the medial, lateral, ventral, and dorsal walls of the external iliac branches of a clear, flow-through replica of a porcine aorta and its daughter vessels. The outflow from each branch of the replica was controlled so that the infrarenal aortic flow rate and the flow partition at the aortic trifurcation were the same for all experiments. LDV measurements were made with flow exiting through both the renal and celiac artery ostia, only the celiac ostium, and neither ostium. The steady flow results indicate that while the outflow through the renal arteries did not have a significant effect on near wall shear rate in the external iliac arteries, the flow through the celiac artery did. However, in pulsatile flow, three indices of near wall velocity in the iliac arteries were unaffected by celiac artery outflow, while a fourth showed a small effect that can be attributed to differences in minimum velocity. These results indicate that reliable simulations of blood flow in the external iliac arteries can be carried out without including the renal and celiac vessels, provided that the correct infrarenal flow wave is used. They also demonstrate that the flow field downstream of a region, such as a branch, that strongly alters the flow, can be nearly independent of the velocity field entering the region. © 2000 Biomedical Engineering Society. PAC00: 8719Uv, 8719Xx  相似文献   

4.
An understanding of how mechanical forces impact cells within valve leaflets would greatly benefit the development of a tissue-engineered heart valve. Previous studies by this group have shown that exposure to constant static pressure leads to enhanced collagen synthesis in porcine aortic valve leaflets. In this study, the effect of cyclic pressure was evaluated using a custom-designed pressure system. Different pressure magnitudes (100, 140, and 170 mmHg) as well as pulse frequencies (0.5, 1.167, and 2 Hz) were studied. Collagen synthesis, cell proliferation, sGAG synthesis, alpha-SMC actin expression, and extracellular matrix (ECM) structure were chosen as markers for valvular biological responses. Results showed that aortic valve leaflets responded to cyclic pressure in a magnitude and frequency-dependent manner. Increases in pressure magnitude (with the frequency fixed at 1.167 Hz) resulted in significant increases in both collagen and sGAG synthesis, while DNA synthesis remained unchanged. Responses to pulse frequency (with the magnitude fixed at 100 mmHg) were more complex. Collagen and sGAG synthesis were increased by 25 and 14% respectively at 0.5 Hz; but were not affected at 1.167 and 2 Hz. In contrast, DNA synthesis increased by 72% at 2 Hz, but not at 0.5 and 1.167 Hz. Under extreme pressure conditions (170 mmHg, 2 Hz), collagen and sGAG synthesis were increased but to a lesser degree than at 170 mmHg, and 1.167 Hz. Cell proliferation was not affected. A notable decline in a-SMC actin was observed over the course of the experiments, although no significant difference was observed between the cyclic pressure and control groups. It was concluded that cyclic pressure affected biosynthetic activity of aortic valve leaflets in a magnitude and frequency dependent manner. Collagen and sGAG synthesis were positively correlated and more responsive to pressure magnitude than pulse frequency. DNA synthesis was more responsive to pulse frequency than pressure magnitude. However, when combined, pressure magnitude and pulse frequency appeared to have an attenuating effect on each other. The number of alpha-SMC actin positive cells did not vary with cyclic pressure, regardless of pulse frequency and pressure magnitude.  相似文献   

5.
This study investigates turbulent flow, based on high Reynolds number, downstream of a prosthetic heart valve using both laser Doppler velocimetry (LDV) and particle image velocimetry (PIV). Until now, LDV has been the more commonly used tool in investigating the flow characteristics associated with mechanical heart valves. The LDV technique allows point by point velocity measurements and provides enough statistical information to quantify turbulent structure. The main drawback of this technique is the time consuming nature of the data acquisition process in order to assess an entire flow field area. Another technique now used in fluid dynamics studies is the PIV measurement technique. This technique allows spatial and temporal measurement of the entire flow field. Using this technique, the instantaneous and average velocity flow fields can be investigated for different positions. This paper presents a comparison of PIV two-dimensional measurements to LDV measurements, performed under steady flow conditions, for a measurement plane parallel to the leaflets of a St. Jude Medical (SJM) bileaflet valve. Comparisons of mean velocity obtained by the two techniques are in good agreement except for where there is instability in the flow. For second moment quantities the comparisons were less agreeable. This suggests that the PIV technique has sufficient temporal and spatial resolution to estimate mean velocity depending on the degree of instability in the flow and also provides sufficient images needed to duplicate mean flow but not for higher moment turbulence quantities such as maximum turbulent shear stress. © 2000 Biomedical Engineering Society. PAC00: 8719Uv, 4262Be, 8780-y  相似文献   

6.
Laser Doppler velocimetry, with a high temporal resolution (1 ms time windows), was used to measure the flow field in two regions (major and minor orifices) near the aortic and mitral valves (Bjork Shiley monostrut Nos. 25 and 27, respectively) of the Penn State artificial heart. The motion of each valve was also investigated using a 1000 frame/s video camera in order to estimate the valve's closing velocity. Fluid velocities in excess of and opposite to valve closing velocity were detected near the valve, providing evidence of squeeze flow. Maximum Reynolds shear stresses of approximately 20,000 dyn/cm2 and time-averaged Reynolds shear stresses of approximately 2000 dyn/cm2 were observed during the regurgitant flow phase. These elevated Reynolds shear stresses suggest that regurgitant jets play a role in the hemolysis and thrombosis associated with tilting disk heart valves in an artificial heart environment. © 1998 Biomedical Engineering Society. PAC98: 8745Hw, 4727Wg, 4279Qx  相似文献   

7.
Tissue engineered heart valves (TEHV) have been observed to respond to mechanical conditioning in vitro by expression of activated myofibroblast phenotypes followed by improvements in tissue maturation. In separate studies, cyclic flexure, stretch, and flow (FSF) have been demonstrated to exhibit both independent and coupled stimulatory effects. Synthesis of these observations into a rational framework for TEHV mechanical conditioning has been limited, however, due to the functional complexity of tri-leaflet valves and the inherent differences of separate bioreactor systems. Toward quantifying the effects of individual mechanical stimuli similar to those that occur during normal valve function, a novel bioreactor was developed in which FSF mechanical stimuli can be applied to engineered heart valve tissues independently or in combination. The FSF bioreactor consists of two identically equipped chambers, each having the capacity to hold up to 12 rectangular tissue specimens (25 × 7.5 × 1 mm) via a novel “spiral-bound” technique. Specimens can be subjected to changes-in-curvature up to 50 mm−1 and uniaxial tensile strains up to 75%. Steady laminar flow can be applied by a magnetically coupled paddlewheel system. Computational fluid dynamic (CFD) simulations were conducted and experimentally validated by particle image velocimetry (PIV). Tissue specimen wall shear stress profiles were predicted as a function of paddlewheel speed, culture medium viscosity, and the quasi-static state of specimen deformation (i.e., either undeformed or completely flexed). Velocity profiles predicted by 2D CFD simulations of the paddlewheel mechanism compared well with PIV measurements, and were used to determine boundary conditions in localized 3D simulations. For undeformed specimens, predicted inter-specimen variations in wall shear stress were on average ±7%, with an average wall shear stress of 1.145 dyne/cm2 predicted at a paddlewheel speed of 2000 rpm and standard culture conditions. In contrast, while the average wall shear stress predicted for specimens in the quasi-static flexed state was ∼59% higher (1.821 dyne/cm2), flexed specimens exhibited a broad intra-specimen wall shear stress distribution between the convex and concave sides that correlated with specimen curvature, with peak wall shear stresses of ∼10 dyne/cm2. This result suggests that by utilizing simple flexed geometric configurations, the present system can also be used to study the effects of spatially varying shear stresses. We conclude that the present design provides a robust tool for the study of mechanical stimuli on in vitro engineered heart valve tissue formation. George C. Engelmayr, Jr. and Lorenzo Soletti are contributed equally.  相似文献   

8.
Three-dimensional laser Doppler velocimetry measurements were acquired in a mock-circulatory loop proximal to a Björk-Shiley monostrut valve in the mitral position, and synchronous ensemble-averaging was applied to form an “average” beat. Two axial locations in the regurgitant flow region of the valve (in the minor orifice) were mapped, and maximum Reynolds shear stresses were calculated. A large spike in regurgitant flow was noted at the beginning of systole, which may be thesqueeze flow phenomenon computed by other researchers. A region of sustained regurgitant flow 50 msec later was the focus of this study. Maximum velocities of ~3.7 mps were noted, and maximum Reynolds shear stresses of ~10,000 dyne/cm2 were calculated. Comparisons were made of two-dimensional (ignoring tangential component)versus three-dimensional shear stresses, and, in this case, in regions of high stress, the differences were insignificant. This suggests that the tangential component of velocity can probably be ignored in similar measurements where the tangential velocity is likely to be small.  相似文献   

9.
A fundamental assumption in mitral valve (MV) therapies is that a repaired or replaced valve should mimic the functionality of the native valve as closely as possible. Thus, improvements in valvular treatments are dependent on the establishment of a complete understanding of the function and mechanical properties of the native normal MV. In a recent study [Grashow et al. ABME 34(2), 2006] we demonstrated that the planar biaxial stress–strain relationship of the MV anterior leaflet (MVAL) exhibited minimal hysteresis and a stress–strain response independent of strain rate, suggesting that MVAL could be modeled as a “quasi-elastic” material. The objective of our current study was to expand these results to provide a more complete picture of the time-dependent mechanical properties of the MVAL. To accomplish this, biaxial stress-relaxation and creep studies were performed on porcine MVAL specimens. Our primary finding was that while the MVAL leaflet exhibited significant stress relaxation, it exhibited negligible creep over the 3-h test. These results furthered our assertion that the MVAL functionally behaves not as a linear or non-linear viscoelastic material, but as an anisotropic quasi-elastic material. These results appear to be unique in the soft tissue literature; suggesting that valvular tissues are unequalled in their ability to withstand significant loading without time-dependent material effects. Moreover, insight into these specialized characteristics can help guide and inform efforts directed toward surgical repair and engineered valvular tissue replacements.  相似文献   

10.
This paper reports the design, manufacturing, and characterization of a new bioreactor dedicated to the development of tissue-engineered heart valve substitutes. First, a comprehensive review of the state of the art in bioreactors is presented and a rigorous classification is put forward. The existing bioreactors found in literature are organized in three groups and discussed with respect to their quality of reproduction compared to the physiological environment. The bioreactor architecture is then decomposed into basic components which may be grouped together in different arrangements, and the well-known Windkessel approach is used to study the global behavior of the system. Then, the new design, which is based on a synthesis of the features of the most evolved systems as well as on new improvements, is explained in detail. Optimal fluid dynamics are obtained with the presented bioreactor through carefully designed components and an advanced computer-controlled actuator. This allows a very accurate reproduction of physiological parameters, namely the pulsating flow rate and pressure. Finally, experimental results of flow rate and pressure waveforms are presented, where an excellent correlation with physiological measurements can be observed.  相似文献   

11.
Compared to native blood vessels, all clinically available blood vessel substitutes perform suboptimally. Numerous approaches to tissue engineer (TE) blood vessels have been pursued using different scaffold materials, cell types, and culture conditions. Several limitations however remain to be overcome prior to the potential application in the arterial system. This study aimed at tissue engineering viable ovine blood vessels suitable for implantation into the systemic circulation of sheep. In recent studies vascular smooth muscle cells (vSMC) were derived by an explant technique. However, in this study we show that homogenous populations of differentiated vSMC were only obtained by enzymatic dispersion as characterized by immunostaining for specific vSMC marker proteins. In contrast the explant method yielded predominantly less differentiated myofibroblast-like cells. Enzymatically derived vSMC were seeded onto P-4-HB scaffolds and incubated either in a pulsatile flow bioreactor or under static conditions. Dynamically cultured TE blood vessel substitutes showed confluent layered tissue formation and were completely water resistant. They displayed significantly increased ECM synthesis, DNA, and protein content as well as vSMC marker expression. Mechanical properties of bioreactor cultured TE blood vessels approached those of native aorta. In conclusion ovine, aortic blood vessel substitutes were successfully created using enzymatically derived vSMC, bioabsorbable scaffolds, and applied shear stress.  相似文献   

12.
No consensus exists regarding the precise contribution of myocardium and the atrioventricular (AV) cushion mesenchyme to the development of leaflets, tendinous cords (TCs) and papillary muscles. Furthermore, the origin and fate of the myocardium embedded in the immature mesenchyme of the AV cushions at the beginning of AV valvulogenesis is controversial. Some authors have suggested that these cells result from a mesenchyme‐to‐myocardium transformation. In contrast, other researchers have concluded that they are derived from the myocardial ventricular wall and the interventricular septum (IVS). On the other hand, it has been assumed that the AV mural and septal leaflets have the same pattern of development. However the supporting structures of the two types of leaflets are anatomically different, which could reflect some differences in the pattern of development. We have therefore investigated the morphogenetic processes involved in sculpting and maturation of the right septal leaflet (RSL) and TCs in embryonic and post‐hatching chicken hearts. The origin and fate of the myocardium embedded in the immature cushion mesenchyme at the beginning of RSL morphogenesis was also studied. For this purpose, scanning electron microscopic analysis, histological studies and immunohistochemical detection of Nkx2.5 and MEF2C were performed. Our findings indicate that the RSL and TCs present a distinct morphogenetic pattern from that of the mural leaflets. Our results also provide evidence that myocardial recruitment from the IVS, but not mesenchyme‐to‐myocardium transformation, participates in the development of the muscular region of the TCs adjacent to the IVS. Anat Rec, 2010. © 2009 Wiley‐Liss, Inc.  相似文献   

13.
14.
目的 探究左心室辅助装置(left ventricular assist device, LVAD)与主动脉吻合角度对主动脉瓣膜的血流动力学影响。方法 分别构建LVAD与主动脉吻合角度为45°、60°、90°的3个主动脉模型和主动脉瓣膜模型,搭建体外搏动台用于体外实验。运用粒子图像测速(particle image velocimetry, PIV)系统,选取心动周期中的3个时刻(T1收缩峰值期,T2瓣膜快速闭合时期和T3舒张峰值期)探究主动脉瓣膜处血流动力学状态。结果 采用速度矢量、涡量、黏性剪切力指标评价LVAD吻合角度对主动脉瓣膜血流动力学的影响。瓣膜快速闭合时期,吻合角度增大时,瓣膜近壁面血流速度、平均涡量和最大黏性剪切力均增大。结论 吻合角度较低时,血流对主动脉瓣膜的冲击速度较小,瓣膜受到较小的剪切力,使瓣膜处于较好的血流动力学环境。研究结果为临床手术中吻合角度的选择提供参考。  相似文献   

15.
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.  相似文献   

16.
Tissue-engineered trileaflet aortic valves are a promising alternative to current valve replacements. However, the mechanical properties of these valves are insufficient for implantation at the aortic position. To simulate the effect of collagen remodeling on the mechanical properties of the aortic valve, a finite element model is presented. In this study collagen remodeling is assumed to be the net result of collagen synthesis and degradation. A limited number of fibers with low initial fiber volume fraction is defined, and depending on the loading condition, the fibers are either synthesized or degraded. The synthesis and degradation of collagen fibers are both assumed to be functions of individual fiber stretch and fiber volume fraction. Simulations are performed for closed aortic valve configurations and the open aortic valve configuration. The predicted fiber directions for the closed configurations are close to the fiber directions as measured in the native aortic valve. The model predicts the evolution in collagen fiber content and the effect of remodeling on the mechanical properties. © 2003 Biomedical Engineering Society. PAC2003: 8715La, 8719Rr, 8710+e, 8780Rb, 8768+z  相似文献   

17.
目的 研究双叶机械瓣膜(bileaflet mechanical heart valve,BMHV)不同植入角度对升主动脉旋动流的影响。方法 基于1位健康自愿者主动脉CT图像,采用计算机数值模拟方法,在定常流条件下,比较研究4种不同瓣膜植入角度(0°、45°、90°和135°)对主动脉旋动流的影响。结果 BMHV植入会严重干扰主动脉内的旋动流,影响升主动脉处的旋动流结构和旋动流强度分布,在瓣膜下游出现扰流区。135°植入角度对旋动流的破坏最大,产生逆向旋动区域最多;0°和45°角植入对旋动流破坏相对较小。植入角为0°时主动脉低壁面剪切应力(<0.5 Pa)所覆盖面积最小。结论 植入角度为0°~45°时,BMHV对升主动脉内旋动流破坏相对较小。因此,对不同患者而言,应根据其主动脉(包括主动脉窦)的空间几何构型进行个性化选择,植入角度可在0°~45°之间确定。  相似文献   

18.
Chondrocyte-seeded scaffolds were cultured in an ultrasound (US)-assisted bioreactor, which supplied the cells with acoustic energy around resonance frequencies (∼5.0 MHz). Polyurethane-polycarbonate (BM), chitosan (CS) and chitosan–n-butanol (CSB) based scaffolds with varying porosities were chosen and the following US regimen was employed: 15 kPa and 60 kPa, 5 min per application and 6 applications per day for 21 days. Non-stimulated scaffolds served as control. For BM scaffolds, US stimulation significantly impacted cell proliferation and depth-independent cell population density compared to controls. The highest COL2A1/COL1A1 ratios and ACAN mRNA were noted on US-treated BM scaffolds compared to controls. A similar trend was noted on US-treated cell-seeded CS and CSB scaffolds, though COL2A1/COL1A1 ratios were significantly lower compared to BM scaffolds. Expression of Sox-9 was also elevated under US and paralleled the COL2A1/COL1A1 ratio. As an original contribution, a simplified mathematical model based on Biot theory was developed to understand the propagation of the incident US wave through the scaffolds and the model analysis was connected to cellular responses. Scaffold architecture influenced the distribution of US field, with the US field being the least attenuated in BM scaffolds, thus coupling more mechanical energy into cells, and leading to increased cellular activity.  相似文献   

19.
目的 结合流体力学模型研究灌注式生物反应器中大段组织工程化骨的构建与多孔支架内流体剪切力的关系。方法 利用灌注式生物反应器对复合骨髓基质干细胞的多孔磷酸三钙支架进行灌注培养。培养基的黏度分别为1.12mPa?s, 2.23mPa?s及3.35mPa?s。通过细胞增殖、成骨分化及组织形态学评价组织工程化骨的构建,建立流体力学模型,求解支架内的流体剪切力。结果 培养基黏度2.23mPa?s组,细胞增殖高于其他组。培养基黏度2.23mPa?s及3.35mPa?s组第28d的碱性磷酸酶活性及第7d后的骨钙素分泌高于1.12mPa?s组。培养基黏度越高,骨桥蛋白的分泌高峰出现越早。28d后,黏度3.35mPa?s组的钙化基质最多。流体力学模型分析,培养基黏度1.12mPa?s, 2.23mPa?s及3.35mPa?s组中,支架内的平均流体剪切力分别为5mPa, 11mPa和15mPa。结论 在利用复合人骨髓基质干细胞的多孔磷酸三钙构建大段组织工程化骨的过程中,15mPa的流体剪切力最有利于组织工程化骨的构建。  相似文献   

20.
Background: Animal and clinical studies have shown that bileaflet mechanical heart valve designs are plagued by thromboembolic complications, with higher rates in the mitral than in the aortic position. This study evaluated the hinge flow dynamic of the 23 mm St. Jude Medical (SJM) Regent and the 23 mm CarboMedics (CM) valves under aortic conditions and compared these results with previous findings under mitral conditions. Method: Velocity and Reynolds shear stress fields were captured using two-component laser Doppler velocimetry. Results: Under aortic conditions, both the SJM and CM hinge flow fields exhibited a strong forward flow pattern during systole (maximum velocities of 2.31 and 1.75 m/s, respectively) and two main leakage jets during diastole (maximum velocities of 3.08 and 2.27 m/s, respectively). Conclusions: Aortic and mitral flow patterns within the two hinges were similar, but with a more dynamic flow during the forward flow phase under aortic conditions. Velocity magnitudes and shear stresses measured under mitral conditions were generally higher than those obtained in the aortic position, which may explain the higher rates of thromboembolism in the mitral implants when compared with the aortic implants.  相似文献   

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