磁驱动血泵溶血分析

测试磁驱动轴流心室辅助装置主体血泵溶血性能。利用计算流体力学(CFD)软件ANSYS,基于红细胞受到切应力和相应曝光时间的计算溶血方法预测血泵溶血性能,计算红细胞粒子随着时间推移在血泵内运动轨迹上受到破坏程度。通过体外模拟循环实验实际测试血泵体外溶血性能,计算得到血泵实际标准溶血指数。CFD计算结果转化的标准溶血指数与实际体外实验结果比较相差较大,与CFD计算简化和实际计算循环周期有很大关系。磁驱动轴流心室辅助装置主体血泵有较好的实际溶血性能,血泵实验期间无不良状况发生,可以进行进一步实验。     

红细胞-固面撞击损伤的实验研究

研究不同撞击速度下,红细胞损伤情况。采用自由落体撞击法进行血液撞击实验,通过血液流变仪对撞击样本进行分析。结果表明,人体血液作为一种特殊的流体,在较高的撞击速度下红细胞有可能发生破裂导致溶血,当撞击速度达到6m/s以上时,红细胞受损破裂趋势增大。血泵的额定转速内,红细胞撞击破碎而造成的损伤并不明显。     

基于CFD的离心式人工心脏泵的溶血预测方法

溶血的定量评价对于人工心脏泵的设计和研究十分重要.本研究应用CFD（computational fluid dynamics）技术,针对两种叶轮设计的离心血泵进行了数值模拟,计算得到了其内部的流线分布.根据溶血、切应力和暴露时间三者之间的幂函数模型,对血泵的溶血进行了预测.最后,用溶血实验结果进行了验证.结果表明,在相同的边界条件下,流线型叶轮泵内的溶血值要小于直叶片叶轮泵,与溶血实验结果一致.可见,应用CFD实现溶血的定量计算是可行的,溶血、切应力和暴露时间之间的幂函数模型能较好地反映血泵的溶血性能.     

离心血泵内部流场数字模拟及溶血分析

血泵是心脏辅助循环装置的核心部件之一,其运行过程中所产生的血栓和溶血超出安全范围将会引发多种并发症,严重者甚至危及病人生命,因此血栓和溶血问题是衡量血泵性能的重要指标也是血泵的重要研究课题。研究表明,溶血主要是由血泵内叶轮的机械运动及血液的复杂流动的高剪切力引起。因此溶血多出现在血液与固壁接触面上及复杂流动的流体问。本次研究的目的是要探索用数值模拟的方法分析离心血泵内部的流场及溶血情况,在研究中通过与上海某医院合作实验采集一种叶片式离心血泵运行过程中的实验数据,再对该叶片式离心血泵内部流场进行数值模拟,通过对比血泵实际运行情况与数值计算结果对其内部血栓和溶血问题进行系统的分析研究,最终数值模拟分析的情况与该血泵在实际运行中的血栓和溶血情况基本相符。通过本次研究探索用数值模拟的方法对血泵的血栓和溶血现象进行分析,特别是对溶血现象进行一定程度的定量分析,此分析结果及分析方法可为血泵优化及临床应用做方法指导之用。     

磁悬浮离心式心室辅助装置的体外溶血测试**

背景：心室辅助装置已广泛应用于心力衰竭患者的治疗。虽然有不同的血泵在国外应用于临床,却很少在国内应用,主要原因是其价格太高。因此在国内研制相对价格较低的能应用于临床的自主血泵迫在眉睫。 目的：测试置入式磁悬浮离心心室辅助装置主体血泵的溶血性能。 方法：通过计算流体力学方法,对磁悬浮离心式心室辅助装置主体血泵内部流场做初步分析。血泵在后负荷100 mm Hg     (1 mm Hg=0.133 kPa)、流量5 L/min 情况下,通过体外模拟血循环系统驱动羊血测试血泵体外溶血性能,计算血泵实际标准溶血指数NIH。 结果与结论：在设计工况下计算流体力学结果显示血泵内部流线平稳,整个流道内部壁面剪切力均在68.5 Pa以下,内部静压力分布均匀,过渡平稳,没有不良区域出现。体外溶血实验测得标准溶血指数NIH值为(0.075±0.017) mg/L。提示血泵驱动叶片及内部流道设计合理,同第3代血泵相比有较好溶血性能。血泵实验期间无不良状况发生,可以进行下一步长期的动物体内实验,进而评估血泵体内血流动力学性能和血泵置入对实验动物脏器的影响。     

介入式微型轴流血泵溶血机理及影响因素分析

溶血性能是判别血泵是否可靠的重要评价因素之一,也是血泵研发过程中的一大难题。本文基于介入式微型轴流血泵的结构特点对其溶血发生机理和关键影响因素进行探究和综述。首先,介绍介入式微型轴流血泵的结构特点:体积小、转速高、叶轮轮缘与泵壳间隙小。然后从剪力溶血和空化溶血两个方面对溶血发生机理进行阐述。最后重点分析导致介入式微型轴流血泵机械溶血的主要力学因素,即剪力和负压。泵内剪力过大或作用时间过长会导致红细胞受损而发生溶血,而负压可能引起血泵空化从而对血液造成损伤。总之,血泵结构设计不当会导致血液在机械运动和湍流运动过程中受到高剪切应力和局部负压的作用产生溶血,所以在设计阶段应全面考虑各因素对血泵溶血的影响。     

螺旋血泵的CFD分析

溶血和血栓是目前国内心室辅助装置不能应用于临床的主要原因。血泵的不良血液动力学特性是导致溶血和血栓的主要因数。计算流体力学（CFD）方法目前被广泛应用于血泵设计,它可以准确有效地反映血泵内部流场状态、血泵压力流量曲线以及血泵内部流场剪切力分布状态等。本研究采用CFD方法对自制螺旋血泵的泵腔、出入流口进行流场分析,内部流场采用三维彩图显示。结果显示CFD分析结果很好的与体外实验结果吻合。血泵血液动力学特性,以及内部血流状态采用CFD方法分析,可以有效地分析血泵血液相溶性方面的问题。     

计算流体动力学在叶轮式心脏泵中的应用研究

造成溶血、血栓等血液破坏现象的内在原因之一是血液的动力学行为。研究表明，不规则的流动模式尤其是切变流中产生的机械切应力直接导致血液的破坏。计算机技术的迅速发展使得微观动力学的数值模拟成为可能。本文针对基于流线型设计的叶轮心脏泵和直叶片叶轮心脏泵，应用计算流体动力学对其内部的流动行为进行了数值模拟。分析两种心脏泵的内流场和切应力分布，认为在相同的边界条件下，流线型设计的叶轮心脏泵要比直叶片心脏泵更符合血液动力学的要求，对血液的破坏较小。     

混流式血泵的数值模拟及性能分析

轴流式血泵转速过高、离心式血泵容易产生流动死区是造成血液损伤的重要原因,而混流式血泵能有效缓解轴流式血泵的转速过高以及离心式血泵的流动死区问题。基于此,本研究旨在探究闭式叶轮混流式血泵的性能效果。通过数值模拟的方法对闭式叶轮混流式血泵进行数值模拟,分析该类型血泵的流场特性及压力分布情况,探讨其水力性能以及可能对红细胞造成的损伤程度,并与半开式叶轮结构混流式血泵的数值模拟结果进行性能对比。结果表明:本研究中的闭式叶轮混流式血泵具有良好的性能,能够安全高效运行。该泵在5 L/min下能够达到100 mm Hg的扬程,血泵内流动均匀,没有明显的涡流、回流以及流动停滞现象,压力分布均匀合理,可有效地避免血栓;溶血指数平均值(HI)为4.99×10^-4,具有良好的血液相容性;与半开式叶轮混流式血泵相比,闭式叶轮混流式血泵扬程和效率更高、溶血指数平均值更小,且具有更好的水力性能及避免血液损伤的能力。通过本文研究结果,或能为闭式叶轮混流式血泵的性能评价提供依据。     

红细胞撞击损伤机理研究及仿真分析

采用薄壁球壳理论及液滴激波理论,研究了旋转叶轮血泵中红细胞-叶片撞击损伤机理,给出了红细胞撞击压力表达式及红细胞膜极限应力数值,并采用ALE有限元法对撞击过程进行仿真,分析不同撞击速度下红细胞形状及应力变化,得到了临界撞击速度数值,并进行了实验验证。     

A relationship between reynolds stresses and viscous dissipation: Implications to red cell damage

Viscous shearing is examined as a mechanism by which turbulent flows can cause cellular damage. The use of Reynolds stress as an indicator of hemolysis is considered, and an alternative measure based on viscous dissipation is proposed. It is shown that under simple flow conditions the Reynolds stresses can be related to viscous dissipation. Data from the literature show that the instantaneous viscous shear stress at which hemolysis occurs is similar to the shear stress thresholds obtained from laminar flow studies. Also, the Kolmogorov length scales for most of the turbulent hemolysis studies are similar to the size of a red blood cell. These observations indicate that, for the jet and couette experiments examined, viscous shearing is an important mechanism in the destruction of erythrocytes by turbulence. However, pressure fluctuations may also contribute to damage for these cells and for cells of similar or larger size.     

Significance of Extensional Stresses to Red Blood Cell Lysis in a Shearing Flow

Traditionally, an empirical power-law model relating hemolysis to shear stress and exposure time has been used to estimate hemolysis related to flow—however, this basis alone has been insufficient in attempts to predict hemolysis through computational fluid dynamics. Because of this deficiency, we sought to re-examine flow features related to hemolysis in a shearing flow by computationally modeling a set of classic experiments performed in a capillary tube. Simulating 21 different flows of varying entrance contraction ratio, flowrate and viscosity, we identified hemolysis threshold streamlines and analyzed the stresses present. Constant damage thresholds for radial and axial extensional stresses of approximately 3000 Pa for exposure times on the order of microseconds were observed, while no such threshold was found for the maximum shear stress or gradient of the shear stress. The extensional flow seen at the entrance of the capillary appears to be most consistently related to hemolysis. An account of how extensional stresses can lead to lysis of a red cell undergoing tank-tread motion in a shearing flow is provided. This work shows that extensional components of the stress tensor are integral in causing hemolysis for some flows, and should be considered when attempting to predict hemolysis computationally.     

Evaluation of Eulerian and Lagrangian models for hemolysis estimation

Hemolysis caused by flow-induced mechanical damage to red blood cells is still a problem in medical devices such as ventricular assist devices (VADs), artificial lungs, and mechanical heart valves. A number of different models have been proposed by different research groups for calculating the hemolysis, and of these, the power law-based models (HI(%)=Ct(α)τ(β)) have proved the most popular because of their ease of use and applicability to a wide range of devices. However, within this power law category of models there are a number of different implementations. The aim of this work was to evaluate different power law-based models by calculating hemolysis in a specifically designed shearing device and a clinical VAD, and comparing the estimated results with experimental measurements of the hemolysis in these two devices. Both the Eulerian scalar transport and all the Lagrangian models had fairly large percentage of errors compared with the experiments (minimum Eulerian 91% and minimum Lagrangian 57%) showing they could not accurately predict the magnitude of the hemolysis. However, the Eulerian approach had large correlation coefficients (>0.99) showing that this method can predict relative hemolysis, which would be useful in comparative analysis, for example, for ranking different devices or for design optimization studies.     

The effect of aortic valve incompetence on the hemodynamics of a continuous flow ventricular assist device in a mock circulation

There is evidence that the incidence of aortic valve incompetence (AI) and other valvular pathologies may increase as more patients are submitted to longer periods of ventricular assist device (VAD) support. There is a need to better understand the mechanisms associated with the onset of these conditions and other possible complications related to the altered hemodynamics of VAD patients. In this study, the effect of AI on the hemodynamic response of continuous flow VAD (C-VAD) patients was measured in a mock loop over a range of pump speeds and level of native cardiac function. Our results showed that, in the presence of sufficient ventricular function, decreasing the C-VAD speed can allow a transition from series to parallel flow. Our study demonstrated that AI reduces the aortic pressure and flow when system impedance is unchanged. AI produces wasteful recirculation that substantially increases the pump work and decreases systemic perfusion, in particular during series flow conditions coupled with higher C-VAD speeds. The hematologic consequence of this regurgitant flow is a much higher exposure to shear for the blood, increasing the likelihood of hemolysis and thrombosis. While a certain degree of AI can be tolerated by a heart with good cardiac function, the consequences of AI for patients with VADs and poor cardiac function are much greater. Valve dysfunction in VAD patients may be related to structural changes in the tissue induced by altered biomechanics and excessive stress.     

Production of erythrocyte microparticles in a sub-hemolytic environment

Microparticles are produced by various cells due to a number of different stimuli in the circulatory system. Shear stress has been shown to injure red blood cells resulting in hemolysis or non-reversible sub-hemolytic damage. We hypothesized that, in the sub-hemolytic shear range, there exist sufficient mechanical stimuli for red blood cells to respond with production of microparticles. Red blood cells isolated from blood of healthy volunteers were exposed to high shear stress in a microfluidic channel to mimic mechanical trauma similar to that occurring in ventricular assist devices. Utilizing flow cytometry techniques, both an increase of shear rate and exposure time showed higher concentrations of red blood cell microparticles. Controlled shear rate exposure shows that red blood cell microparticle concentration may be indicative of sub-hemolytic damage to red blood cells. In addition, properties of these red blood cell microparticles produced by shear suggest that mechanical trauma may underlie some complications for cardiovascular patients.

     

Scaling of Hemolysis in Needles and Catheters

Hemolysis in clinical blood samples leads to inaccurate assay results and often to the need for repeated blood draws. In vitro experiments were conducted to determine the influence on hemolysis in phlebotomy needles and catheters of pressure difference, cannula diameter, and cannula material. Fresh blood from five human volunteers was forced from a syringe inside a pressurized chamber through 14, 18, and 22 gauge 304 stainless steel needles and polyurethane and Teflon^® catheters, all 40 mm long. Hemolysis was measured in the samples by a spectrophotometer. It was found that hemolysis increased with increases in pressure difference and cannula diameter and no consistent trend could be identified with regard to cannula material. The pressure differences required for significant hemolysis were above those typical of clinical venipuncture blood draws. While there was substantial variability among individuals, the hemolysis values scaled with exponent S=(t/t₀)[( / ₀)–1]², where t is the characteristic duration of shear, t₀ is a time constant, is the wall shear stress, and ₀ is the wall shear stress threshold below which no hemolysis occurs. A hemolysis threshold including both time and shear stress was also defined for S=constant. The threshold implies that a threshold shear stress exists below which erythrocytes are not damaged for any length of exposure time, but that red cells may be damaged by an arbitrarily short period of exposure to sufficiently large shear stress. © 1998 Biomedical Engineering Society. PAC98: 8745Hw, 8722-q     

Leakage flow rate and wall shear stress distributions in a biocentrifugal ventricular assist device

In previous studies, the radial and tangential leakage flow velocities in the gap between the rotating impeller and the pump casing of a biocentrifugal ventricular assist device (VAD) model were obtained by hot wire. Based on the velocities obtained, the leakage flow rate through the clearance gap between the impeller and the stationary casing, as well as the wall shear stress distributions on the inner surface of the stationary casing, can be determined. By integrating the radial velocities numerically, the leakage flow rate through the clearance gap was found to be 6.43 x 10(-4) m3/s under operating conditions, which is 25.7% of the inlet flow. This is equivalent to approximately 1.7 L/min in the prototype. The leakage flow rate was found to be 5.22 x 10(-4) m3/s and 3.66 x 10(-4) m3/s under fully opened and fully closed conditions, respectively. The double volute design significantly affected wall shear stress distributions, with the high wall shear stress region concentrated at the beginning of the splitter plate under all three flow conditions. In contrast, the high wall shear stress region could only be observed at the cutwater in the fully closed condition. The highest wall shear stress was found to be 44.1 Pa, which is much lower than the threshold values that cause hemolysis. On the other hand, the lowest wall shear stress was found to be 21.31 Pa. This wall shear stress level is much higher than the shear stress required to disrupt aggregates of blood cells and platelets. These findings explain why hemolysis and thrombosis are at the low level in the clearance gap of this VAD.     

Alterations in bovine endothelial histidine decarboxylase activity following exposure to shearing stresses

Endothelial cell injury produced by elevated intravascular stresses represents a causative factor in atherogenesis. Of the various hemodynamic stresses, those imposed by shear have been particularly implicated. Since it is well established that tissue histamine synthesis increases following various forms of injury, and since endothelial histamine synthesis is considerably greater than that of other wall components, the histidine decarboxylase (HD) activity of primary cultures of bovine endothelium following 1.5 hr exposure to various shearing stress intensities has been examined. Results indicate that with respect to paired, nonstressed control cultures, endothelial cell HD activity increases 2.8-, 2.3-, and 3.7-fold when subjected to mean shearing stresses of 2.8, 4.6, and 6.2 dynes/cm², respectively. These data indicate endothelial histamine synthesis is extremely sensitive to shearing stress exposure, and suggest this enzyme system may represent an enzymatic coupler between hemodynamic stresses and subsequent permeability alterations.     

Shear stress effects on bacterial adhesion, leukocyte adhesion, and leukocyte oxidative capacity on a polyetherurethane.

Infection of implanted cardiovascular biomaterials still occurs despite inherent host defense mechanisms. Using a rotating disk system, we investigated Staphylococcus epidermidis and polymorphonuclear leukocyte (PMN) adhesion to a polyetherurethane urea (PEUU-A') under shear stress (0-17.5 dynes/cm2) for time periods up to 6 h. In addition, the superoxide (SO) release capacity of PMNs after transient exposure to PEUU-A' under shear stress was determined. Bacterial adhesion in phosphate-buffered saline (PBS) showed a linear shear dependence, decreasing with increasing shear stress. Overall adhesion in PBS decreased with time. However, bacterial adhesion in 25% human serum was similar for all time points up to 360 min. Adhesion was observed at all shear levels, displaying no shear dependence. In contrast, PMN adhesion demonstrated a strong shear dependence similarly for times up to 240 min, decreasing sharply with increasing shear stress. Although PMNs preexposed to shear stress showed a slightly diminished SO release response compared to fresh cells for all stimuli, it was not statistically significant regardless of the stimulus. We conclude that circulating leukocytes are unable to adhere in regions of high shear which may contain adherent bacteria. In addition, exposure to PEUU-A' and shear stress (in the range 0-18 dynes/cm2) is insufficient to cause a depression in the oxidative response of PMNs.