Idit Avrahami

Influence of microcalcifications on vulnerable plaque mechanics using FSI modeling

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.

Computational studies of resonance wave pumping in compliant tubes

The valveless impedance pump is a simple design that allows the producion or amplification of a flow without the requirement for valves or impellers. It is based on fluid-filled flexible tubing, connected to tubing of different impedances. Pumping is achieved by a periodic excitation at an off-centre position relative to the tube ends. This paper presents a comprehensive study of the fluid and structural dynamics in an impedance pump model using numerical simulations. An axisymmetric finite-element model of both the fluid and solid domains is used with direct coupling at the interface. By examining a wide range of parameters, the pumps resonance nature is described and the concept of resonance wave pumping is discussed. The main driving mechanism of the flow in the tube is the reflection of waves at the tube boundary and the wave dynamics in the passive tube. This concept is supported by three different analyses: (i) time-dependent pressure and flow wave dynamics along the tube, (ii) calculations of pressure–flow loop areas along the passive tube for a description of energy conversion, and (iii) an integral description of total work done by the pump on the fluid. It is shown that at some frequencies, the energy given to the system by the excitation is converted by the elastic tube to kinetic energy at the tube outlet, resulting in an efficient pumping mechanism and thus significantly higher flow rate. It is also shown that pumping can be achieved with any impedance mismatch at one boundary and that the outlet configuration does not necessarily need to be a tube.

Unsteady Effects on the Flow Across Tilting Disk Valves

The present study simulates numerically the flow across two-dimensional tilting disk models of mechanical heart valves. The time-dependent Navier-Stokes equations are solved to assess the importance of unsteady effects in the fully open position of the valve. Flow cases with steady or physiological inflow conditions and with fixed or moving valves are solved. The simulations lead into mixed conclusions. It is obvious that steady inflow cases that account for vortex shedding only cannot model realistic physiological cases. In cases with imposed physiological inflow, the details of the flow field for fixed and moving valves might differ in the fully open position as well, although the gross features are quite similar. The fixed valve case consistently results in safe estimations of several critical quantities such as the axial force, the maximal shear stress on the valve, or the transvalvular pressure drop. Thus, fixed valve simulations can provide useful information for the design of prosthetic heart valves, as long as the properties in the fully open position only are sought.

Resonant pumping in a multilayer impedance pump

This paper introduces the concept of multilayer impedance pump, a novel pumping mechanism inspired by the embryonic heart structure. The pump is a composite two-layer fluid-filled elastic tube featuring a thick gelatinous internal. Pumping is based on the impedance pumping mechanism. In an impedance pump, elastic waves are generated upon external periodic compressions of the elastic tube. These waves propagate along the tubes walls, reflect at the tubes extremities, and drive the flow in a preferential direction. The originality in the multilayer impedance pump design relies on the use of the thick internal gelatinous layer to amplify the elastic waves responsible for the pumping. As a consequence, only small excitations are needed to produce significant flow. This fully coupled fluid-structure interaction problem is solved for the flow and the structure using the finite element method over a relevant range of frequencies of excitation. Results show that the multilayer impedance pump is a complex system that exhibits a resonant response. Flow output and inner wall motion are maximal when the pump is actuated at the resonant frequency. The wave interaction mechanism present in an impedance pump is described here in details for the case of a multilayer impedance pump. Using energy balance for the passive portion of the elastic tube, we show that the elastic tube itself works as a pump and that at resonance maximum energy transmission between the elastic tube and the fluid occurs. Finally, the pump is especially suitable for many biomedical applications.

Can vortices in the flow across mechanical heart valves contribute to cavitation

Cavitation in mechanical heart valves is traditionally attributed to the hammer effect and to squeeze and clearance flow occurring at the moment of valve closure. In the present study, an additional factor is considered—the contribution of vortex flow. Using a computational fluid dynamics analysis of a 2D model of a tilting disk mitral valve, we demonstrate that vortices may form in the vicinity of the inflow side of the valve. These vortices roll up from shear layers emanating from the valve tips during regurgitation. A significant decrease in the pressure at the centre of the vortices is found. The contribution of the vortex to the total pressure drop at the instant of closure is of the order of 70 mmHg. Adding this figure to the other pressure drop sources that reach 670 mmHg, it might be that this is the deciding factor that causes the drop in blood pressure below vapour pressure. The total pressure drop near the upper tip (750 mmHg) is larger than near the lower tip (670 mmHg), indicating a preferential location for cavitation inception, in agreement with existing experimental findings.

A 3D rotary renal and mesenchymal stem cell culture model unveils cell death mechanisms induced by matrix deficiency and low shear stress

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.

The Hemodynamics of the Berlin Pulsatile VAD and the Role of its MHV Configuration

The 3D flow in a model of the Berlin ventricular assist device (VAD) chamber with monoleaflet valves placed in S-shape conduits was simulated numerically. The blood flow dynamics were described in terms of flow patterns, velocity, pressure, and shear stress. The hemodynamic properties and the VADs potential risk for thrombosis were evaluated in terms of mixing and washout properties, and global estimations of platelet level of activation (LOA). In order to evaluate the role of valves on the flow in the chamber, the flow in a model with bileaflet valves in straight conduits was simulated and compared with the original case. The results showed that in both models a large rotating flow was developed in the chamber during filling. This vortex filled the entire chamber and moved constantly up to the peak ejection phase, resulting in relatively low shear stress (up to 0.4 Pa) and no lasting stagnation regions. Significant shear stresses were found near the valves with higher values near the outlet valve in both models. The configuration of valves and conduits had a large effect on VAD washout and mixing properties, with advantage to the bileaflet model. However, since the bileaflet valves exhibited higher shear stresses, higher LOA were found for the bileaflet model.

Numerical investigation of a novel aortic cannula aimed at reducing cerebral embolism during cardiovascular bypass surgery.

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.

Investigation of Risks for Cerebral Embolism Associated With the Hemodynamics of Cardiopulmonary Bypass Cannula: A Numerical Model

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.

Peripheral microcirculatory hemodynamic changes in patients with myocardial ischemia

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.