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1.
Bioengineering (Basel) ; 11(3)2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38534512

ABSTRACT

Percutaneous mechanical circulatory support (MCS) devices are designed for short-term treatment in cases of acute decompensated heart failure as a bridge to transplant or recovery. Some of the known complications of MCS treatments are related to their hemodynamics in the aorta. The current study investigates the effect of MCS on the aortic flow. The study uses combined experimental and numerical methods to delineate complex flow structures. Particle image velocimetry (PIV) is used to capture the vortical and turbulent flow characteristics in a glass model of the human aorta. Computational fluid dynamics (CFD) analyses are used to complete the 3D flow in the aorta. Three specific MCS configurations are examined: a suction pump with a counterclockwise (CCW) rotating impeller, a suction pump with a clockwise (CW) rotating impeller, and a discharge pump with a straight jet. These models were examined under varying flow rates (1-2.5 L/min). The results show that the pump configuration strongly influences the flow in the thoracic aorta. The rotating impeller of the suction pump induces a dominant swirling flow in the aorta. The swirling flow distributes the incoming jet and reduces the turbulent intensity near the aortic valve and in the aorta. In addition, at high flow rates, the local vortices formed near the pump are washed downstream toward the aortic arch. Specifically, an MCS device with a CCW rotating impeller induces a non-physiological CCW helical flow in the descending aorta (which is opposite to the natural helical flow), while CW swirl combines better with the natural helical flow.

2.
Heliyon ; 10(4): e25744, 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38404887

ABSTRACT

Hydrogen-based Fuel Cells (FCs) hold significant potential as energy conversion technologies. In a previous study, we presented a pump-based hydrogen generator (PHG) that utilizes a catalytic reaction between sodium borohydride (NaBH4) powder and water. The pump circulates the water solution through the powder chamber in a closed-loop reaction. The PHG demonstrated clear advantages over alternative hydrogen sources in terms of both safety and energy density. However, as operating time increases, the solution in the closed-loop PHG becomes saturated, causing the reaction rate to decline. This limitation can be overcome in cases where an external water source is available, such as marine vehicles, drones equipped with water recovery systems from their fuel cells, or systems located near pipelines. In such scenarios, introducing freshwater feeding and product emission offers intriguing possibilities for significantly enhancing the fuel's energy density and extending its effective operation time. Our current research introduces an innovative concept: a dual-cycle generator (DCG) that effectively overcomes the issue of solution saturation over time. It achieves this by combining solution circulation with freshwater feeding and product emission. Our study employed a DCG prototype to examine various operating modes and to demonstrate the effectiveness of this approach. The DCG achieved a calculated energy density for the fuel of 3868 Wh/kg, with 93% H2 extraction yield from the powder. Our findings reveal substantial improvements in terms of extended operation duration (81%), increased hydrogen flow rate (36%), enhanced energy density (33%), and improved H2 yield extraction from the powder (39%). This methodology holds promise for mobile applications or off-grid systems situated in proximity to a water source.

3.
Membranes (Basel) ; 14(1)2023 Dec 22.
Article in English | MEDLINE | ID: mdl-38248694

ABSTRACT

In air-breathing proton exchange membrane fuel cells (Air PEM FCs), a high rate of water evaporation from the cathode might influence the resistance of the membrane electrode assembly (MEA), which is highly dependent on the water content of the Nafion membrane. We propose a dead-end hydrogen anode as a means of intermediate storage of water/humidity for self-humidification of the membrane. Such an inflatable bag integrated with a single lightweight MEA FC has the potential in blimp applications for anode self-humidification. A dynamic numerical water balance model, validated by experimental measurements, is derived to predict the effect of MEA configuration, and the membrane's hydration state and water transfer rate at the anode on MEA resistance and performance. The experimental setup included humidity measurements, and polarization and electrochemical impedance spectroscopy tests to quantify the effect of membrane hydration on its resistance in a lightweight MEA (12 g) integrated with an inflatable dead-end hydrogen storage bag. Varying current densities (5, 10, and 15 mA/cm2) and cathode humidity levels (20, 50, and 80%) were examined and compared with the numerical results. The validated model predicts that the hydration state of the membrane and water transfer rate at the anode can be increased by using a thin membrane and thicker gas diffusion layer.

4.
Comput Methods Biomech Biomed Engin ; 25(4): 424-438, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34320881

ABSTRACT

We suggest improving minimally-invasive stenosis severity estimation, using a combination of existing geometry-based methods with Transluminal Attenuation Gradient measurements. Instead of local flow values, the method uses flow distribution ratios along the entire tree. The tree geometry is used to derive a lumped model and predict the 'theoretical' ratios in each bifurcation, while attenuation measurements are used for extracting 'actual' ratios. The discrepancies between the measured and the theoretical values are utilized to assess a functional degree of stenosis. Our experimental and numerical analyses show that the quantitative value of discrepancy is proportional to stenosis severity, regardless of boundary conditions.


Subject(s)
Coronary Stenosis , Blood Flow Velocity , Constriction, Pathologic , Coronary Angiography/methods , Coronary Stenosis/diagnostic imaging , Coronary Vessels , Humans , Predictive Value of Tests , Severity of Illness Index
5.
Micromachines (Basel) ; 12(11)2021 Nov 21.
Article in English | MEDLINE | ID: mdl-34832843

ABSTRACT

During aerial missions of fuel-cell (FC) powered drones, the option of FC edge cooling may improve FC performance and durability. Here we describe an edge cooling approach for fixed-wing FC-powered drones by removing FC heat using the ambient air during flight. A set of experiments in a wind tunnel and numerical simulations were performed to examine the efficiency of FC edge cooling at various flight altitudes and cruise speeds. The experiments were used to validate the numerical model and prove the feasibility of the proposed method. The first simulation duplicated the geometry of the experimental setup and boundary conditions. The calculated temperatures of the stack were in good agreement with those of the experiments (within ±2 °C error). After validation, numerical models of a drone's fuselage in ambient air with different radiator locations and at different flight speeds (10-30 m/s) and altitudes (up to 5 km) were examined. It was concluded that onboard FC edge cooling by ambient air may be applicable for velocities higher than 10 m/s. Despite the low pressure, density, and Cp of air at high altitudes, heat removal is significantly increased with altitude at all power and velocity conditions due to lower air temperature.

6.
J Biomech ; 121: 110351, 2021 05 24.
Article in English | MEDLINE | ID: mdl-33794471

ABSTRACT

The aortic arch aneurysm is a complex disease that requires branching of one or more aortic arch vessels and can be fatal if left untreated. In this in vitro study, we examine the effect of the treatment approach on the unsteady hemodynamics and blood perfusion to the upper vessel's in models of an aortic arch aneurysm, and of the three common repair approaches: open-chest surgical repair, chimney, and hybrid approach. A particle image velocimetry method was used to quantify the unsteady hemodynamics in the four models simulated in a mock circulatory loop, to evaluate unsteady hemodynamic parameters and measure perfusion to the brain and the upper body. According to the findings, in terms of perfusion to the brain and upper body, the surgery model has the highest flow rate comparing to the other models in most heart-rate conditions. It also shows oscillatory parameters in the upper vessels which in normal arteries are correlated with a better arterial function. Between the two endovascular procedures, the hybrid model exhibits slightly better hemodynamic characteristics than the chimney model, with lower shear stresses and more oscillatory flow and WSS in the upper vessels. The hybrid model had lower perfusion flow rates to upper vessels during rest conditions (90BPM). However, unlike the other models, perfusion in the hybrid model increased with heart rate, thus at 135 BPM, it results in flow rate to upper vessels similar to that of the chimney model. The results of this study may shed light on future endograft' design and placement techniques.


Subject(s)
Aortic Aneurysm , Blood Vessel Prosthesis Implantation , Endovascular Procedures , Aorta, Thoracic/surgery , Blood Vessel Prosthesis , Heart Rate , Hemodynamics , Humans , Perfusion , Prosthesis Design , Stents , Treatment Outcome
7.
Clin Biomech (Bristol, Avon) ; 78: 105075, 2020 08.
Article in English | MEDLINE | ID: mdl-32535477

ABSTRACT

BACKGROUND: Reduced coronary flow reserve in aortic stenosis and after transcatheter aortic valve implantation is usually attributed to physiological factors taking place during systole, such as an increase in coronary resistance, and backward waves intensity. In this paper, we suggest an additional factor related to the diastolic hemodynamics in the aortic root. METHODS: We measured left ventricle, aortic and coronary pressure and coronary perfusion in in-vitro models of healthy, aortic stenosis and an artificial valve at different heart rates and cardiac output conditions, to isolate the effect of hemodynamic factors in the aortic root during diastole. FINDINGS: Our results show that during diastole, coronary perfusion depends on the pressure gradient between the aorta and the coronary inlet. This aorta-coronary pressure gradient is influenced by the hemodynamic flow field in the aortic root. The ratio between the aorta-coronary pressure gradient magnitude in stress to that under rest conditions of a healthy model is ten times higher than the same ratio in the aortic stenosis model and twice higher as compared to the artificial valve model result. The coronary flow reserve of the healthy model is correspondingly higher compared to the artificial valve and the aortic stenosis models. These results are in agreement with the clinical evidence. INTERPRETATION: This study supports the hypothesis of a hemodynamic mechanism in the aortic root that increases coronary flow during rest but reduces the coronary flow reserve in aortic stenosis and artificial valve cases. The results may provide valuable insights regarding valve design.


Subject(s)
Aortic Valve/physiology , Aortic Valve/physiopathology , Coronary Circulation , Heart Rate , Hemodynamics , Aortic Valve/surgery , Aortic Valve Stenosis/physiopathology , Aortic Valve Stenosis/surgery , Humans , Transcatheter Aortic Valve Replacement
8.
Comput Math Methods Med ; 2018: 4517652, 2018.
Article in English | MEDLINE | ID: mdl-30510592

ABSTRACT

The carotid bifurcation tends to develop atherosclerotic stenoses which might interfere with cerebral blood supply. In cases of arterial blockage, the common clinical solution is to remove the plaque via carotid endarterectomy (CEA) surgery. Artery closure after surgery using primary closures along the cutting edge might lead to artery narrowing and restrict blood flow. An alternative approach is patch angioplasty which takes longer time and leads to more during-surgery complications. The present study uses numerical methods with fluid-structure interaction (FSI) to explore and compare the two solutions in terms of hemodynamics and stress and strain fields developed in the artery wall.


Subject(s)
Carotid Artery Diseases/physiopathology , Carotid Artery Diseases/surgery , Carotid Sinus/physiopathology , Carotid Sinus/surgery , Endarterectomy, Carotid/methods , Models, Cardiovascular , Angioplasty/methods , Biomechanical Phenomena , Carotid Artery Diseases/pathology , Carotid Sinus/pathology , Computer Simulation , Hemodynamics , Humans , Mathematical Concepts , Suture Techniques , Vascular Closure Devices , Wound Closure Techniques
9.
Biomech Model Mechanobiol ; 17(2): 319-338, 2018 Apr.
Article in English | MEDLINE | ID: mdl-28929246

ABSTRACT

During diastole, coronary perfusion depends on the pressure drop between the myocardial tissue and the coronary origin located at the aortic root. This pressure difference is influenced by the flow field near the closing valve leaflets. Clinical evidence is conclusive that patients with severe aortic stenosis (AS) suffer from diastolic dysfunction during hyperemia, but show increased coronary blood flow (CBF) during rest. Transcatheter aortic valve implantation (TAVI) was shown to decrease rest CBF along with its main purpose of improving the aortic flow and reducing the risk of heart failure. Physiological or pathological factors do not provide a clear explanation for the increase in rest CBF due to AS and its decrease immediately after TAVI. In this manuscript, we present a numerical study that examines the impact of AS and TAVI on CBF during rest conditions. The study compares the hemodynamics of five different 2D numerical models: a baseline "healthy valve" case, two AS cases and two TAVI cases. The analysis used time-dependent computational fluid-structure interaction simulations of blood flow in the aortic root including the dynamics of the flexible valve leaflets and the varying resistance of the coronary arteries. Despite its simplifications, our 2D model succeeded to capture the major effects that dominate the hemodynamics in the aortic root and to explain the hemodynamic effect that leads to the changes in CBF found in in vitro and clinical studies.


Subject(s)
Aortic Valve/physiology , Coronary Circulation/physiology , Hemodynamics/physiology , Numerical Analysis, Computer-Assisted , Humans , Models, Cardiovascular , Pressure , Systole/physiology , Time Factors , Transcatheter Aortic Valve Replacement
10.
J Biomech ; 50: 158-165, 2017 01 04.
Article in English | MEDLINE | ID: mdl-27876371

ABSTRACT

Aortic arch aneurysm is a complex pathology which requires coverage of one or more aortic arch vessels. In this study we explore the hemodynamic behavior of the aortic arch in aneurysmatic and treated cases with three currently available treatment approaches: Surgery Graft, hybrid Stent-Graft and chimney Stent Graft. The analysis included four models of the time-dependent fluid domains of aneurysmatic arch and of the surgery, hybrid and chimney endovascular techniques. Dimensions of the models are based on typical anatomy, and boundary conditions are based on typical physiological flow. The simulations used computational fluid dynamics (CFD) methods to delineate the time-dependent flow dynamics in the four geometric models. Results of velocity vectors, flow patterns, blood pressure and wall shear stress distributions are presented. The results delineate disturbed and recirculating flow in the aortic arch aneurysm accompanied with low wall shear stress and velocities, compared to a uniformly directed flow and nominal wall shear stress (WSS) in the model of Surgery graft. Out of the two endograft procedures, the hybrid procedure clearly exhibits better hemodynamic performances over the chimney model, with lower WSS, lower pressure drop and less disturbed and vortical flow regions. Although the chimney procedure requires less manufacturing time and cost, it is associated with higher risk rates, and therefore, it is recommended only for emergency cases. This study may shed light on the hemodynamic factors for these complications and provide insight into ways to improve the procedure.


Subject(s)
Aneurysm/physiopathology , Aorta, Thoracic/physiology , Blood Vessel Prosthesis Implantation , Models, Cardiovascular , Stents , Aneurysm/therapy , Aorta, Thoracic/transplantation , Endovascular Procedures , Hemodynamics/physiology , Humans , Stress, Mechanical , Treatment Outcome
11.
PLoS One ; 11(11): e0166426, 2016.
Article in English | MEDLINE | ID: mdl-27893801

ABSTRACT

Arterial wall shear stress (WSS) parameters are widely used for prediction of the initiation and development of atherosclerosis and arterial pathologies. Traditional clinical evaluation of arterial condition relies on correlations of WSS parameters with average flow rate (Q) and heart rate (HR) measurements. We show that for pulsating flow waveforms in a straight tube with flow reversals that lead to significant reciprocating WSS, the measurements of HR and Q are not sufficient for prediction of WSS parameters. Therefore, we suggest adding a third quantity-known as the pulsatility index (PI)-which is defined as the peak-to-peak flow rate amplitude normalized by Q. We examine several pulsating flow waveforms with and without flow reversals using a simulation of a Womersley model in a straight rigid tube and validate the simulations through experimental study using particle image velocimetry (PIV). The results indicate that clinically relevant WSS parameters such as the percentage of negative WSS (P[%]), oscillating shear index (OSI) and the ratio of minimum to maximum shear stress rates (min/max), are better predicted when the PI is used in conjunction with HR and Q. Therefore, we propose to use PI as an additional and essential diagnostic quantity for improved predictability of the reciprocating WSS.


Subject(s)
Arteries/physiology , Pulsatile Flow/physiology , Atherosclerosis/diagnosis , Heart Rate , Hemodynamics , Humans , Shear Strength
12.
Biomed Pharmacother ; 74: 83-8, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26349967

ABSTRACT

BACKGROUND: Patients with coronary heart disease demonstrate changes in skin microcirculation and a decrease in cutaneous blood mass. OBJECTIVE: The goal of this study was to assess the feasibility of diagnosing myocardial ischemia based on peripheral microcirculatory variables. METHODS: The skin microcirculatory measurements were monitored using an LPT system comprising a Laser Doppler Flowmeter (LDF), a photoplethysmograph (PPG) and a transcutaneous oxygen tension device (tc-PO2). Concurrently, heart rate and blood pressure were monitored. Measurements were performed before and after exercise stress test. Subjects were divided into ischemic (20) and nonischemic (27) patients based on myocardial perfusion imaging (MPI). RESULTS: The results indicate differences in LPT variables between ischemic and nonischemic patients following exercise, while no differences in the central variable values were observed between the two groups. CONCLUSIONS: Peripheral microcirculatory variables may be useful for non-invasive assessment of myocardial ischemia. The system has clinical potential for sensitive and noninvasive monitoring of vital variables during medical procedures in clinics, as well as in home care for patients who suffer from ischemic cardiac diseases.


Subject(s)
Hemodynamics/physiology , Microcirculation/physiology , Myocardial Ischemia/diagnosis , Skin/blood supply , Adult , Aged , Blood Pressure/physiology , Exercise Test , Feasibility Studies , Female , Heart Rate/physiology , Humans , Laser-Doppler Flowmetry , Male , Middle Aged , Myocardial Ischemia/pathology , Myocardial Perfusion Imaging/methods , Oxygen/metabolism , Photoplethysmography
13.
Comput Biol Med ; 52: 102-10, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25033021

ABSTRACT

INTRODUCTION: Restenosis is strongly attributed to stresses caused by stent-artery interactions generated in the artery after balloon angioplasty. Numerical methods are often used to examine the stent-artery mechanical interactions. To overcome the extensive computational requirements demanded by these simulations, simplifications are needed. OBJECTIVE: We introduce simplified models to calculate the mechanical interactions between net-structured stents and arteries, and discuss their validity and implications. METHODS: 2D simplified numerical models are suggested, which allow cost effective assessment of arterial stresses and the potential damage factor (DF). In these models, several contact problems were solved for arteries with hyper elastic mechanical properties. Stresses were calculated for a large range of cases and for different numerical model types. The effects of model simplifications, oversizing mismatch and stenosis rate and length and symmetry on the resulting stresses were analyzed. RESULTS & CONCLUSIONS: Results obtained from planar 2D models were found in good agreement with results obtained from complex 3D models for cases with axisymmetric constant or varying stenosis. This high correlation between the results of 3D cases with varying stenosis and the more simple 2D cases can be used as a simplified and convenient tool for calculating the arterial wall stresses in complex cases. Maximal stresses obtained by the 2D model with an asymmetric stenosis are lower than the maximal stresses obtained in the axisymmetric case with the same stenosis percentage. Therefore, axisymmetric models may provide the worst-case estimation values for a stent of interest.


Subject(s)
Arteries/pathology , Models, Statistical , Stents , Vascular Diseases/therapy , Humans
14.
J Thorac Cardiovasc Surg ; 148(2): 668-75, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24521961

ABSTRACT

OBJECTIVE: Intraoperative cerebral events are mainly caused by emboli generated by operative manipulation of the aorta. This study aimed to delineate the distribution profiles of emboli with 2 widely used cannulae and a third novel research cannula that simultaneously produces forward flow and backward suction to extract emboli from the distal aorta during cardiac surgery. METHODS: The current in vitro study used a silicone model of the aortic arch and branches. The main outcome measure was the distribution profile of embolic particles of different sizes to the aortic branches; 2 commercial cannulae and a third novel cannula with and without suction were used. The research cannula was examined at different suction levels and the amount of particles retrieved was measured. RESULTS: For the research curved-tip cannula, most of the small emboli were released into the brachiocephalic trunk in the model (P < .05). For the straight-tip cannula, most of the small emboli were released into the descending aorta (P < .05). Regarding the commercial curved-tipped cannula, most of the small emboli were released into the brachiocephalic trunk (47.14% ± 4.78%; P < .05) and the medium and large emboli were predominantly released into the descending aorta. Using suction, the research cannula retrieved most of the emboli released into the aorta for all particle sizes (50%-83%; P < .05). CONCLUSIONS: A straight-tip cannula may be safer in terms of cerebral embolic consequences during cardiac surgery. Furthermore, the use of the research aortic cannula may be beneficial in the cardiac surgery setting by reducing the postoperative risk for stroke.


Subject(s)
Aorta/surgery , Cardiac Catheters , Cardiac Surgical Procedures/instrumentation , Embolic Protection Devices , Intracranial Embolism/prevention & control , Stroke/prevention & control , Cardiac Surgical Procedures/adverse effects , Humans , Intracranial Embolism/etiology , Materials Testing , Models, Anatomic , Models, Cardiovascular , Particle Size , Prosthesis Design , Risk Factors , Stroke/etiology , Suction
15.
Artif Organs ; 37(10): 857-65, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24138494

ABSTRACT

Cerebral emboli originating in the ascending aorta are a major cause of noncardiac complications following cardiac surgery. The hemodynamics of the aortic cannula has been proven to play a significant role in emboli generation and distribution. The aim of the current study was to perform a thorough numerical investigation in order to examine the effect of the design and orientation of the cannula used during cardiopulmonary bypass on the risk to develop cerebral embolism. Hemodynamic analyses compared numerical models of 27 cases consisting of six different cannula orientations, four aortic anatomies, and three cannula designs. The cannula designs included a straight-tip (ST) cannula, a moderately curved tip cannula (TIP1 ), and a sharp-angle curved cannula (TIP2 ). Outcome measures included hemodynamic parameters such as emanating jet velocity, jet velocity drop, maximal shear stress, aortic wall reaction, emboli pathlines and distribution between upper and lower vessels, and stagnation regions. Based on these parameters, the risks for hemolysis, atheroembolism, and cerebral embolism were evaluated and compared. On one hand, the jet emerging from the ST cannula generated large wall-shear stress at the aortic wall; this may have triggered the erosion and distribution of embolic atheromatous debris from the aortic arch. On the other hand, it diverted more emboli from the clamp region to the descending aorta and thus reduced the risk for cerebral embolism. The TIP1 cannula demonstrated less shear stress on the aortic wall and diverted more emboli from the clamp region toward the upper vessels. The TIP2 cannula exhibited a stronger emanating jet, higher shear stress inside the cannula, and highly disturbed flow, which was more stagnant near the clamp region. Current findings support the significant impact of the cannula design and orientation on emboli generation and distribution. Specifically, the straight tip cannula demonstrated a reduced risk of cerebral embolism, which may be pivotal in the clinical setting.


Subject(s)
Aorta, Thoracic/surgery , Cardiopulmonary Bypass/instrumentation , Catheters/adverse effects , Intracranial Embolism/etiology , Vascular Access Devices/adverse effects , Aorta/anatomy & histology , Aorta/surgery , Aorta, Thoracic/anatomy & histology , Equipment Design , Hemodynamics , Humans , Models, Cardiovascular , Risk Factors
16.
J Biomech ; 46(2): 354-61, 2013 Jan 18.
Article in English | MEDLINE | ID: mdl-23195623

ABSTRACT

The generation of emboli during cardiopulmonary bypass (CPB) is profoundly affected by the hemodynamic properties of the aortic cannula used in the current study. The aim of the current work was to numerically investigate the hemodynamic efficiency and feasibility of a novel, backward suction cannula (BSC), designed to drastically reduce the potential risk for cerebral emboli (CEP). In line with the standard cannulae, the BSC provides oxygenated blood from the CPB machine through its primary lumen. However, the unique feature of the BSC lies in its secondary lumen, which is used to suck blood and embolic matter back from the surgical field to the CPB machine for filtration. Analysis included a numerical investigation of the hemodynamic characteristics of 44 different models, encompassing various anatomic orientations, cannula types, cannula orientations and flow conditions. Hemodynamic efficacy and CEP were assessed via trajectories of particle released from the surgical region, while the cannula feasibility was evaluated through potential for atheroembolism (AP) and index for hemolysis (IH). Differences between the investigated cannulae in terms of these measures were tested using analyses of variance tests (ANOVAs). Results indicate that the BSC exhibited a significant improvement of the cannula performance in terms of CEP with no significant change in the risk for other hemodynamic complications, such as hemolysis or atheroembolism (AP and IH). These findings suggest the advantageous use of the BSC in the clinical setting for its potential to diminish the risk for cerebral emboli, which presents the most pertinent cause of noncardiac complications following open heart surgery.


Subject(s)
Coronary Artery Bypass/adverse effects , Hemodynamics , Intracranial Embolism/prevention & control , Models, Cardiovascular , Postoperative Complications/prevention & control , Vascular Access Devices , Aorta , Coronary Artery Bypass/instrumentation , Coronary Artery Bypass/methods , Humans , Intracranial Embolism/physiopathology , Postoperative Complications/physiopathology
17.
Cancer Lett ; 272(2): 345-54, 2008 Dec 18.
Article in English | MEDLINE | ID: mdl-18723276

ABSTRACT

Anchorage-independence is a hallmark of invasive cancer. The setback of the classical poly-HEMA static matrix detachment (SMD) anoikis model is the absence of dynamic fluid circulation, resulting in cell aggregates. We addressed this problem by developing a novel 3D cell culture dynamic matrix detachment (DMD) model with a turbulent-free laminar flow, yielding a very low shear stress. In this study, we focused on melanoma cells where apoptosis was evaluated both via annexin V flow cytometry and caspase cleavage. The DMD model was superior to SMD in the induction of melanoma cell death and in revealing a shift from apoptosis to necrotic cell death, as evident by failure to activate caspase 9 and a decrease in annexin V stain. Combination of DMD with cisplatin could further accentuate necrotic cell death in cisplatin-resistant melanoma cells. Thus, the DMD model may be a useful matrix deprivation model to identify necrotic vs. apoptotic cell death pathways.


Subject(s)
Apoptosis , Melanoma, Experimental/pathology , Models, Biological , Necrosis , Animals , Blotting, Western , Cell Line, Tumor , Flow Cytometry , Mice
18.
Nephrol Dial Transplant ; 23(6): 2071-80, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18344240

ABSTRACT

BACKGROUND: In epithelial and endothelial cells, detachment from the matrix results in anoikis, a form of apoptosis, whereas stromal and cancer cells are often anchorage independent. The classical anoikis model is based on static 3D epithelial cell culture conditions (STCK). METHODS: We characterized a new model of renal, stromal and mesenchymal stem cell (MSC) matrix deprivation, based on slow rotation cell culture conditions (ROCK). This model induces anoikis using a low shear stress, laminar flow. The mechanism of cell death was determined via FACS (fluorescence-activated cell sorting) analysis for annexin V and propidium iodide uptake and via DNA laddering. RESULTS: While only renal epithelial cells progressively died in STCK, the ROCK model could induce apoptosis in stromal and transformed cells; cell survival decreased in ROCK versus STCK to 40%, 52%, 62% and 7% in human fibroblast, rat MSC, renal cell carcinoma (RCC) and human melanoma cell lines, respectively. Furthermore, while ROCK induced primarily apoptosis in renal epithelial cells, necrosis was more prevalent in transformed and cancer cells [necrosis/apoptosis ratio of 72.7% in CaKi-1 RCC cells versus 4.3% in MDCK (Madin-Darby canine kidney) cells]. The ROCK-mediated shift to necrosis in RCC cells was further accentuated 3.4-fold by H(2)O(2)-mediated oxidative stress while in adherent HK-2 renal epithelial cells, oxidative stress enhanced apoptosis. ROCK conditions could also unveil a similar pattern in the LZ100 rat MSC line where in ROCK 44% less apoptosis was observed versus STCK and 45% less apoptosis versus monolayer conditions. Apoptosis in response to oxidative stress was also attenuated in the rat MSC line in ROCK, thereby highlighting rat MSC transformation. CONCLUSIONS: The ROCK matrix-deficiency cell culture model may provide a valuable insight into the mechanism of renal and MSC cell death in response to matrix deprivation.


Subject(s)
Apoptosis/physiology , Mesangial Cells/cytology , Mesenchymal Stem Cells/cytology , Oxidative Stress/physiology , Animals , Anoikis/physiology , Carcinoma, Renal Cell/pathology , Cell Death/physiology , Cell Line, Tumor , Cell Survival , Cells, Cultured , Dogs , Epithelial Cells/cytology , Epithelial Cells/physiology , Extracellular Matrix , Fluorescent Antibody Technique , Humans , Melanoma/pathology , Mesangial Cells/physiology , Mesenchymal Stem Cells/physiology , Mice , Models, Theoretical , Probability , Rats , Reactive Oxygen Species/analysis , Sensitivity and Specificity , Stress, Mechanical
19.
J Biomech ; 41(5): 1111-8, 2008.
Article in English | MEDLINE | ID: mdl-18258240

ABSTRACT

Sudden heart attacks remain one of the primary causes of premature death in the developed world. Asymptomatic vulnerable plaques that rupture are believed to prompt such fatal heart attacks and strokes. The role of microcalcifications in the vulnerable plaque rupture mechanics is still debated. Recent studies suggest the microcalcifications increase the plaque vulnerability. In this manuscript we present a numerical study of the role of microcalcifications in plaque vulnerability in an eccentric stenosis model using a transient fluid-structure interaction (FSI) analysis. Two cases are being compared (i) in the absence of a microcalcification (ii) with a microcalcification spot fully embedded in the fibrous cap. Critical plaque stress/strain conditions were affected considerably by the presence of a calcified spot, and were dependent on the timing (phase) during the flow cycle. The vulnerable plaque with the embedded calcification spot presented higher wall stress concentration region in the fibrous cap a bit upstream to the calcified spot, with stress propagating to the deformable parts of the structure around the calcified spot. Following previous studies, this finding supports the hypothesis that microcalcifications increase the plaque vulnerability. Further studies in which the effect of additional microcalcifications and parametric studies of critical plaque cap thickness based on plaque properties and thickness, will help to establish the mechanism by which microcalcifications weaken the plaque and may lead to its rupture.


Subject(s)
Calcinosis/pathology , Coronary Stenosis/pathology , Models, Biological , Atherosclerosis/pathology , Coronary Vessels/pathology , Rheology/methods , Stress, Mechanical
20.
Artif Organs ; 30(7): 529-38, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16836734

ABSTRACT

This article addresses the growing need for comprehensive tools to investigate the hemodynamics of ventricular assist devices (VADs) in general and sac-type VADs in particular. Numerical simulations can be very helpful in these efforts. However, full simulation of flow inside sac-type VADs poses several key problems, among them simulation of the mechanical heart valves and calculation of the motion of flexible walls. We present a simplified three-dimensional (3D) numerical model of a sac-VAD chamber. The walls in the simplified model are defined to move according to experimental measurements, and the valves are modeled in fully open or fully closed positions. The model is validated by comparison to a fully coupled fluid-structure interaction numerical simulation and to experimental measurements using continuous digital particle image velocimetry. Our results demonstrate that the flexible wall motion is sensitive to changes in pressure distribution inside the chamber. However, small variations in wall motion do not significantly affect the global features of flow inside the chamber. Therefore, the simplified model can be used to predict the 3D time-dependent flow field in the VAD.


Subject(s)
Heart-Assist Devices , Models, Cardiovascular
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