The effect of aneurismal-wall mechanical properties on patient-specific hemodynamic simulations:two clinical case reports

Hemodynamic factors such as the wall shear stress play an important role in the pathogenesis and treatment of cerebral aneurysms. In present study, we apply computational fluid-structure interaction analyses on cerebral aneurysms with two different constitutive relations for aneurismal wall in order to investigate the effect of the aneurismal wall mechanical properties on the simulation results. We carry out these analyses by using two patient-specific models of cerebral aneurysms of different sizes located in different branches of the circle of Willis. The models are constructed from 3D rotational angiography image data and blood flow dynamics is studied under physiologically representative waveform of inflow. From the patient models analyzed in this investigation, we find that the deformations of cerebral aneurysms are very small. But due to the nonlinear character of the Navier-Stokes equations, these small deformations could have significant influences on the flow characteristics. In addition, we find that the aneurismal-wall mechanical properties have great effects on the deformation distribution of the aneurysm, which also affects the wall shear stress distribution and flow patterns. Therefore, how to define a proper constitutive relation for aneurismal wall should be considered carefully in the hemodynamic simulation.

Effects of electroacupuncture on c-Fos expression in the spinal cord and brain of rats with chronic visceral hypersensitivity

BACKGROUND： Visceral hypersensitivity is the main cause of irritable bowel syndrome, c-Fos is a marker of visceral hypersensitivity in the central nervous system. Electroacupuncture can relieve chronic visceral hypersensitivity in rats, but the mechanism is still unknown. OBJECTIVE： To identify c-Fos expression in the spinal cord and cerebral cortex of rats with chronic visceral hypersensitivity, and to test the effects of electroacupuncture on pain sensitivity in rats with chronic visceral hypersensitivity. DESIGN, TIME AND SETTING： A randomized controlled animal experiment was performed at the Animal E：~perimental Center, Shanghai University of Traditional Chinese Medicine, from January to April, 2007. MATERIALS： A total of 24 neonatal, male, Sprague Dawley rats, aged five days old, were equally and randomly assigned into a normal group, a model group, and an electroacupuncture group. Rabbit anti-rat c-Fos antibody and Evision secondary antibody kits （Sigma, USA）, diaminobenzidine kit （Dako, Denmark）, and an LD202H electroacupuncture apparatus （Huawei, Beijing, China） were used in this study. METHODS： Neonatal rats from the model and electroacupuncture groups were used to establish rat models of chronic visceral hypersensitivity by the saccule stimulation method. After model establishment, 0.25 mm diameter electric needles were inserted into Tianshu （ST 25） and Shangjuxu （ST37） at a depth of approximately 0.5 cm, with an square wave （alternating current frequency at 100/20 Hz, amplitude ranged 0.2-0.6 ms, intensity at 1 mA） once for 20 minutes, once a day, for seven days. Rats in the normal and model groups were not treated. MAIN OUTCOME MEASURES： Following 7 days of treatment, c-Fos expression in the spinal cord and cerebral cortex was detected by immunohistochemistry. After the first electroacupuncture treatment, abdominal withdrawal reflex scores were investigated to evaluate the pain threshold for chronic visceral hypersensitivity in rats. RESULTS： Visceral hypersensitivity increased c-Fos staining （P 〈 0.05）, and electroacupuncture significantly decreased the number of these cells to near normal levels （P 〉 0.05）. Abdominal withdrawal reflex scores were significantly lower in the electroacupuncture and normal groups than in the model group （P 〈 0.05） and were similar between the electroacupuncture and normal groups （P 〉 0.05）. CONCLUSION： Electroacupuncture decreases c-Fos expression in the spinal cord and cerebral cortex and increases pain threshold in a chronic visceral hypersensitivity model in rats.

Numerical Analyses of Idealized Total Cavopulmonary Connection Physiologies with Single and Bilateral Superior Vena Cava Assisted by an Axial Blood Pump

Our study evaluated the hemodynamic performance of an axial flow blood pump surgically implanted in idealized total cavopulmonary connection(TCPC)models.This blood pump was designed to augment pressure from the inferior vena cava(IVC)to the pulmonary circulation.Two Fontan procedures with single and bilateral superior vena cava(SVC)were compared to fit the mechanical supported TCPC physiologies.Computational fluid dynamics(CFD)analyses of two Pump-TCPC models were performed in the analyses.Pressure-flow characteristics,energy efficiency,fluid streamlines,hemolysis and thrombosis analyses were implemented.Numerical simulations indicate that the pump produces pressure generations of 1 mm to 24 mm Hg for rotational speeds ranging from 2000 RPM to 5000 RPM and flow rates of 2 LPM to 4 LPM.Two surgical models incorporated with the pump were found to be insignificant in pressure augmentation and energy boost.The risk assessment of blood trauma and thrombosis generation was evaluated representatively through blood damage index(BDI),particle resident time(PRT)and relative resistant time(RRT).The hemolysis and thrombosis analyses declare the advantage of the pump supported bilateral SVC surgical scheme in balancing flow distribution and reducing the risk of endothelial cell destruction and trauma generation.

液态栓塞剂栓塞脑动静脉畸形的计算流体力学建模与仿真

大脑动静脉畸形(AVMs)的血管内栓塞通常需要注射液态栓塞剂(LEAs)以减少畸形处的血流.在临床实践中,需要事先仔细规划注射LEAs的供血动脉以及LEAs的剂量.计算流体动力学可以模拟LEAs在畸形团内的注射过程,并在术前评估不同操作的治疗效果.应用多孔介质模型避免了AVMs的几何建模困难,并重现了血管瘤内复杂的血管网络结构.采用多相流模拟了LEAs与血液之间的相互作用.LEAs的黏度由其溶质乙烯-乙醇共聚物(EVOH)的浓度确定.通过求解物质输运方程计算了溶剂二甲基亚矾(DMSO)的扩散过程.通过构建EVOH浓度与黏度之间的关系,模拟了LEAs的凝固过程.LEAs的注射和凝固的数值模拟方法在两个特定患者的AVMs上进行了测试。计算预测了LEAs在畸形团内的流动方向。通过三维染可以很好地可视化注射的LEAs的形态.进行了定量分析,包括供血动脉和引流静脉的流量变化.利用计算流体动力学(CFD)方法可以模拟LEAs栓塞AVMs的过程,以展示不同栓塞手术规划的治疗效果,并确定最佳治疗方案.

Mechanisms of Qi-blood circulation and Qi deficiency syndrome in view of blood and interstitial fluid circulation

OBJECTIVE: Based on comparison between fundamental theories of Traditional Chinese Medicine (TCM) and Western Medicine (WM) and modern scientific research on meridians, we find that "Qi" in TCM is closely related to tissue fluid. In this study, the essence of Qi is explored in the view of circulation of blood and interstitial fluid. METHODS: Because the concept of Qi is complicated, Qi deficiency syndrome (QDS) is chosen to probe the relationship between of Qi deficiency and Qi-blood circulation (QBC). We analyze Qi-blood theory in terms of WM, set up a hemodynamic model to describe QBC, and review clinical research on QDS in the view of blood-interstitial fluid circulation. RESULTS: QDS is caused by imbalances of substance exchanges between blood and interstitial fluid, leading to an increase in the interstitial liquid volume or a decrease in nutrients and retention ofmetabolic wastes in interstitial fluid. CONCLUSION: This study describes the essence of Qi, providing support for further research on theories of Qiand Qi-blood circulation inTCM.

Dynamics of Calcium Signal and Leukotriene C_(4) Release in Mast Cells Network Induced by Mechanical Stimuli and Modulated by Interstitial Fluid Flow

Mast cells(MCs)play an important role in the immune system.Through connective tissues,mechanical stimuli activate intracellular calcium signaling pathways,induce a variety of mediators including leukotriene C4(LTC4)release,and affect MCs’microenvironment.This paper focuses on MCs’intracellular calcium dynamics and LTC4 release responding to mechanical stimuli,explores signaling pathways in MCs and the effect of interstitial fluid flow on the transport of biological messengers and feedback in the MCs network.We use a mathematical model to show that(i)mechanical stimuli including shear stress induced by interstitial fluid flow can activate mechano-sensitive(MS)ion channels on MCs’membrane and allow Ca^(2+)entry,which increases intracellular Ca^(2+)concentration and leads to LTC4 release;(ii)LTC4 in the extracellular space(ECS)acts on surface cysteinyl leukotriene receptors(LTC4R)on adjacent cells,leading to Ca^(2+)influx through Ca^(2+)release-activated Ca^(2+)(CRAC)channels.An elevated intracellular Ca^(2+)concentration further stimulates LTC4 release and creates a positive feedback in the MCs network.The findings of this study may facilitate our understanding of the mechanotransduction process in MCs induced by mechanical stimuli,contribute to understanding of interstitial flow-related mechanobiology in MCs network,and provide a methodology for quantitatively analyzing physical treatment methods including acupuncture and massage in traditional Chinese medicine(TCM).

Finite element models and molecular dynamic simulations for studying the response of mast cell under mechanical activation

In micropipette aspiration experiment,increasing mechanical stress applied to cell membrane induced degranulation of mast cell as well as a current that could be inhibited by an inhibitor, which is specific for the transient receptor potential vanilloid(TRPVs) channels. To determine the sensitivity of TRPVs to membrane strain and tension, and to gain new insights into the activation mechanism of TRPVs, finite element models of mast cell and molecular dynamic simulations of human aquaporin-1are presented. During the finite element simulations, the cell membrane sustained to micropipette aspiration was simulated, and the strain distribution along membrane thickness direction was obtained. Besides, combining the finite element models of osteoblast aspirated into micropipette and other compared models, we examined the relationship between cell mechanical attributes and mechanical stimulations and presented a new perspective to determine the cell equivalent elastic modulus. Considering the indetermination of TRPV crystal structure, human aquaporin-1, one kind of the channel membrane proteins,substituting for TRPV, has been studied with molecular dynamic(MD) simulations, under different external lateral tensions which have been obtained in mast cell finite element simulations, to investigate the mechanical stimulation effects on the membrane channels. The simulations show that human aquaporin-1 undergoes significant conformational change and expands in accordance with lateral tension, which not only confirms the tendency of the previous electrophysiological experiments but also leads us to a better understanding of TRPVs. The multi-scale study combining finite element simulation and MD simulation is a significant breakthrough in the field of mechanical mechanism in cell system.

A dynamic model of calcium signaling in mast cells and LTC_4 release induced by mechanical stimuli

Mast cells(MCs) play an important role in the immune system. It is known that mechanical stimuli can induce intracellular Ca2+signal and release a variety of mediators, including leukotriene C4(LTC4), leading to other cellular and physiological changes. In this paper, we present a mathematical model to explore signalling pathways in MCs, by including cellular mechanisms for intracellular Ca2t increase and LTC4release in response to mechanical stimuli, thapsigargin(TG, SERCA pump inhibitor), and LTC4 stimuli. We show that(i) mechanical stimuli activate mechano-sensitive ion channels and induce inward ion fluxes and Ca2?entry which increases intracellular Ca2+concentration and releases LTC4;(ii) TG inhibits SERCA pumps, empties the internal Ca2+ stores,which activates Ca2+release-activated Ca2+channels and results in sustained intracellular Ca2+increase; and(iii)LTC4activates receptors on MCs surface and increases intracellular Ca2+concentration. Our results are consistent with experimental observations, and furthermore, they also reveal that mechanical stimuli can increase intracellular Ca2+even when LTC4release is blocked, which suggests a feed forward loop involved in LTC4production. This study may facilitate our understanding of the mechanotransduction process in MCs and provide a useful modeling tool for quantitatively analyzing immune mechanisms involving MCs.

Experimental exploration and research prospect of physical bases and functional characteristics of meridians

The physical basis of meridians and acupoints (acupuncture points) is in a complex system mainly of connective tissue and interwoven with the blood capillaries, nerves, lymph vessels,etc. Elements of Ca, P, K, Fe, Zn, Mn, etc are found concentrated in the deep connective tissue structures in locations corresponding to acupoints. On this physical basis, the specific waveband of high efficiency for transmission of infrared rays exists in the collagenous fibre in a liquid crystal state. The development direction and new idea of researching on acupuncture and meridians are discussed.