Pulsatile Flow Rate Research Articles

Haemodynamic effects of non-Newtonian fluid blood on the abdominal aorta before and after double tear rupture

ObjectivesIntimal tears caused by aortic dissection can weaken the arterial wall and lead to aortic aneurysms. However, the effect of different tear states on the blood flow behaviour remains complex. This study uses a novel approach that combines numerical haemodynamic simulation with in vitro experiments to elucidate the effect of arterial dissection rupture on the complex blood flow state within the abdominal aneurysm and the endogenous causes of end-organ malperfusion. Materials and methodsBased on the CT imaging data and clinical physiological parameters, the overall arterial models including aortic dissection and aneurysm with single tear and double tear were established, and the turbulence behaviours and haemodynamic characteristics of arterial dissection and aneurysm under different blood pressures were simulated by using non-Newtonian flow fluids with the pulsatile blood flow rate of the clinical patients as a cycle, and the results of the numerical simulation were verified by in vitro simulation experiments. ResultsHemodynamic simulations revealed that the aneurysm and single-tear false lumen generated a maximum pressure of 320.591 mmHg, 267 % over the 120 mmHg criterion. The pressure differential generates reflux, leading to a WSS of 2247.9 Pa at the TL inlet and blood flow velocities of up to 6.41 m/s inducing extend of the inlet. DTD Medium FL instantaneous WP above 120 mmHg Standard 151 % Additionally, there was 82.5 % higher flow in the right iliac aorta than in the left iliac aorta, which triggered malperfusion. Thrombus was accumulated distal to the tear and turbulence. These results are consistent with the findings of the in vitro experiments. ConclusionsThis study reveals the haemodynamic mechanisms by which aortic dissection induces aortic aneurysms to produce different risk states. This will contribute to in vitro simulation studies as a new fulcrum in the process of moving from numerical simulation to clinical trials.

Applications of a novel reciprocating positive displacement pump in the simulation of pulsatile arterial blood flow.

Pulsatile arterial blood flow plays an important role in vascular system mechanobiology, especially in the study of mechanisms of pathology. Limitations in cost, time, sample size, and control across current in-vitro and in-vivo methods limit future exploration of novel treatments. Presented is the verification of a novel reciprocating positive displacement pump aimed at resolving these issues through the simulation of human ocular, human fingertip and skin surface, human cerebral, and rodent spleen organ systems. A range of pulsatile amplitudes, frequencies, and flow rates were simulated using pumps made of 3D printed parts incorporating a tubing system, check valve and proprietary software. Volumetric analysis of 430 total readings across a flow range of 0.025ml/min to 16ml/min determined that the pump had a mean absolute error and mean relative error of 0.041 ml/min and 1.385%, respectively. Linear regression analysis compared to expected flow rate across the full flow range yielded an R2 of 0.9996. Waveform analysis indicated that the pump could recreate accurate beat frequency for flow ranges above 0.06ml/min at 70BPM. The verification of accurate pump output opens avenues for the development of novel long-term in-vitro benchtop models capable of looking at fluid flow scenarios previously unfeasible, including low volume-high shear rate pulsatile flow.

CFD MODELS FOR ANEURYSM ANALYSES AND THEIR USE IN IDENTIFYING THROMBOSIS FORMATION AND RISK ASSESSMENT

In this paper, the blood transport has been investigated using the single- and the two-phase methods. In the two-phase Euler–Euler approach, the blood is represented by two interpenetrating continua where the dispersed red blood cells (RBCs) of non-Newtonian characteristics are suspended in the continuous Newtonian plasma. The results of the two-phase model, where the RBC’s phase is assumed to be Carreau–Yasuda fluid, are validated against the experimental data. Furthermore, comparative analyses were performed in two patient-specific aneurysms, which indicated that for a given pulsatile flow rate, the two-phase blood approach is vitally advantageous over the single-phase assumption, and revealed a deeper inflow penetration, more complex flow structures and denser flow diversion zones in the aneurysm sac. It was obvious that the high OSI values calculated by the two-phase model covered much wider regions than the values predicted by the single-phase model. It was equally crucial that these regions coincided with the TAWSS values lower than the threshold that the single-phase approach can predict. Apparently, the single-phase model failed to spot sites of high rupture risk. The results were further exploited to identify the RBCs aggregation regions as, for example, the concave structures and narrow paths in the saccular aneurysms, for their possible use as the precursors of the thrombus formation.

Radial and Axial Displacement of the Initially-Tensioned Orthotropic Arterial Wall Under the Influence of Harmonics and Wave Reflection

Abstract This study examines radial and axial displacement of the arterial wall under the influence of harmonics and wave reflection for the role of axial wall displacement in pulsatile wave propagation. The arterial wall is modeled as an initially-tensioned thin-walled orthotropic tube. In conjunction with three pulsatile parameters in blood flow, a free wave propagation analysis is conducted on the governing equations of the arterial wall and no-slip conditions at the blood-wall interface to obtain the frequency equation and pulsatile parameter expressions under different harmonics. The influence of wave reflection is then added to pulsatile parameter expressions. With the harmonic values of measured pulsatile pressure and blood flow rate at the ascending aorta in the literature, the waveforms of radial wall displacement, axial wall displacement, and wall shear stress are calculated under different orthotropicity and axial initial tension. The developed theory and calculated results indicate that (1) difference in waveform between blood flow rate, wall shear stress, and axial wall displacement is caused by harmonics, rather than wave reflection; (2) Axial wall displacement does not affect blood flow rate, radial wall displacement, and wall shear stress; (3) Besides wall shear stress, radial wall displacement gradient also contributes to axial wall displacement and its contribution is adjusted by axial initial tension; (4) different wave reflections only noticeably affect the maximum and minimum values of wall shear stress; and (5) The amplitude and waveform of axial wall displacement are predominantly dictated by axial elasticity and axial initial tension, respectively.

Effects of Pulsatile Flow Rate and Shunt Ratio in Bifurcated Distal Arteries on Hemodynamic Characteristics Involved in Two Patient-Specific Internal Carotid Artery Sidewall Aneurysms: A Numerical Study.

The pulsatile flow rate (PFR) in the cerebral artery system and shunt ratios in bifurcated arteries are two patient-specific parameters that may affect the hemodynamic characteristics in the pathobiology of cerebral aneurysms, which needs to be identified comprehensively. Accordingly, a systematic study was employed to study the effects of pulsatile flow rate (i.e., PFR−I, PFR−II, and PFR−III) and shunt ratio (i.e., 75:25 and 64:36) in bifurcated distal arteries, and transient cardiac pulsatile waveform on hemodynamic patterns in two internal carotid artery sidewall aneurysm models using computational fluid dynamics (CFD) modeling. Numerical results indicate that larger PFRs can cause higher wall shear stress () in some local regions of the aneurysmal dome that may increase the probability of small/secondary aneurysm generation than under smaller PFRs. The low and relatively high oscillatory shear index () could appear under a smaller PFR, increasing the potential risk of aneurysmal sac growth and rupture. However, the variances in PFRs and bifurcated shunt ratios have rare impacts on the time-average pressure () distributions on the aneurysmal sac, although a higher PFR can contribute more to the pressure increase in the ICASA−1 dome due to the relatively stronger impingement by the redirected bloodstream than in ICASA−2. CFD simulations also show that the variances of shunt ratios in bifurcated distal arteries have rare impacts on the hemodynamic characteristics in the sacs, mainly because the bifurcated location is not close enough to the sac in present models. Furthermore, it has been found that the vortex location plays a major role in the temporal and spatial distribution of the WSS on the luminal wall, varying significantly with the cardiac period.

A cadaveric perfused model with antegrade arteriovenous pulsatile circulation: a new tool for teaching endovascular skills.

Background:The benefits of using cadaveric humans in surgical training are well documented, and knowledge of the latest endovascular techniques is essential in the daily practice of vascular surgeons. Our study explores the feasibility of an affordable human cadaveric model with pulsatile and heated antegrade perfusion for reliable and reproducible endovascular or surgical simulation.Methods:We undertook cannulation of 7 human cadavers embalmed in a saturated salt solution to create a left-to-right central perfusion with a heated solution, from the ascending thoracic aorta to the right atrium. To that end, we used surgically created carotidojugular and femorofemoral arteriovenous fistulas. Biomedical engineers designed a prototype pump for pulsatile circulation. We monitored invasive blood pressure and temperature. We used this model for training for endovascular thoracic aortic procedures and open vascular surgeries.Results:The prototype pump achieved a pulsatile flow rate of 4.7 L/min. Effective cadaveric perfusion was achieved for several hours, not only with an arterioarterial pathway but also with arteriovenous circulation. The arterial pressures and in situ temperatures accurately restored vascular functions for life-like conditions. This new model made it possible to successfully perform thoracic endovascular aortic repair, subclavian artery stenting and simulation of abdominal open vascular trauma management. The saturated salt solution method and a specifically designed pump improved cost competitiveness.Conclusion:Endovascular simulation on human cadavers, optimized with the pulsatile and heated perfusion system, can be a dynamic adjunct for surgical training and familiarization with new devices. This reproducible teaching tool could be relevant in all surgery programs.

Hemodynamic flow characteristics at stenosed artery: Numerical analysis of three-dimensional patient-specific aortic–cerebral vasculature exposed to progressive carotid stenosis

Progression of carotid stenosis (CS) significantly reduces blood flow in the affected arteries and alters both proximal and distal hemodynamics. While conventional studies consider only the stenosis region for analysis, an extended larger arterial domain of aortic–cerebral vasculature is used to avoid artificial modeling of the inlet condition to the carotid region and facilitate automatic flow redistribution during CS progression. The fluid domain was constructed and simulated using an open-source package SimVascular, and three patient models with five stenosis cases each were created using medical images. Newtonian, incompressible, and rigid-wall conditions were assumed because of the high computational burden, and boundary conditions of the lumped Windkessel and pulsatile flow rate were implemented for the outlets and inlet, respectively. We present a novel index called circulation core fraction (CCF) to quantify and visualize the stenosis-driven hemodynamics; the CCF is developed from the benchmark backward-facing step problem and compares the representative recirculation to the total volume. Thus, CCF in the post-stenotic region increases during CS progression regardless of patient-specific features whereas that in the pre-stenotic region exhibits patient-specific nature despite the incremental tendency. Streamlines with custom sources show a helical vortex with recirculation and artery-wise flow streams that vary during CS progression. We also report transitional patterns in both the pulsatility index (PI) contours and Q-criterion, where the PI values shift from high–low–high to high–low–low across the stenosis, and the latter is nearly absent at 0% and 95% but mostly present at 50% and 75% CS.

Numerical study of the effect of hemodynamic variables on LDL concentration through the single layer of the Left Anterior Descending coronary artery (LAD) under the heart pulse.

Heart attack is one of the most common causes of death in the world. Coronary artery disease is the most recognized cause of heart attack whose onset and progression have been attributed to low-density lipoprotein (LDL) passing through the wall of the artery. In this paper, hemodynamic variables as well as the concentration of LDL through the coronary porous artery at the Left Anterior Descending coronary artery (LAD), and its first diagonal branch (D1) under the heart motion investigated using computational simulation. The geometry that has been studied in this paper is the first bifurcation of Left Anterior Descending (LAD) that has been placed on a perimeter of hypothetical sphere representative of the heart geometry. Sinusoidal variations of sphere radii, simulated pulsating movement of the heart. Blood has been considered as a Newtonian and incompressible flow with pulsatile flow rate and real physiological profile. The plasma filtration boundary condition used over the walls in order to simulate the concentration of LDL to a one-layer artery wall. Variations in the concentration of LDL on the artery wall and its relation to oscillation on shear stress on the artery wall under different conditions are presented. Moreover, the effects of the pulsating inlet flow and dynamic movement of the artery are explored. The results declared that minimum shear stress and maximum LDL concentration take place at the bifurcation and on the myocardial wall which is in complete agreement with clinical studies. Furthermore, it has been shown that the heart pulse has a slight effect on the average time of concentration (0.1% increase); however, by analyzing all time steps, one could observe that the maximum concentration rises in some time steps; where this increases the possibility of LDL presence and helps them diffuse inside the artery wall.

Physiologically relevant platform for an advanced in vitro model of the vascular wall: focus on in situ fabrication and mechanical maturation

The mechanical stimulation applied on engineered vascular constructs in perfusion bioreactors has been shown to be beneficial for their maturation. The level of mechanical stimulation applied on these constructs depends on the flow parameters of the circuit (e.g., fluid viscosity, flow rate, frequency, and pressure). As a group, these parameters are often overlooked in the literature, and they rarely meet the physiological values of the blood flow. For this reason, the level of circumferential stretching and shear stress that blood vessels experience in the human body are rarely reproduced. In this work, we reported the development of a physiologically relevant platform for (1) the in situ fabrication of vascular wall models based on collagen gel, and (2) their maturation under physiological levels of mechanical stimulation in a perfusion bioreactor (pulsatile flow rate of 100 mL/min, frequency of 1 Hz, pressure of 80–120 mmHg, and viscosity of 4 cP). One week of dynamic maturation oriented the seeded cells into the circumferential direction, increased the deposition of collagen and key elastin fiber-related proteins, and improved the mechanical properties in terms of tensile equilibrium elastic modulus (by 110%) and strength at break (by 63%) when compared to the static condition. In addition to the maturation study under selected physiologically relevant mechanical stimulation (such as adult, fetal, child, and hypertension conditions), the platform might also be used as a relevant in vitro testing system for new drugs or pro-active coating to medical devices (such as stents, endografts, and vascular prostheses) expected to trigger specific mechanisms or activities in vascular cells composing the arterial wall.

Methodologies towards approximating the volume displacement by a roller in a roller-type peristaltic pump

The roller volume displacement (RVD) is the volume that a roller displaces within the tube of a roller-type peristaltic pump when it is being occluded by the roller, not to be confused with the pump volume displacement. The RVD is generally measured in order to model and simulate the pump by means of first principle modeling. The rate of change of this volume displacement (referred to as the roller induced flow rate) gives rise to the pulsatile flow rate and pressure commonly associated with roller-type peristaltic pumps. In addition to this, the volume displaced by the roller reduces the amount of transported fluid per revolution of the motor, effectively altering the average volume flow rate of the pump. The ability to obtain this flow rate without physically measuring it is advantageous for both design and modeling applications. This paper provides methods of approximating the volume displaced by the roller in a roller-type peristaltic pump. The approximations are derived from the pump and process tube dimensions. Several methods of varying complexity and accuracy are provided for approximating the maximum volume displaced by the roller. An angle dependent approximation allows for approximating this volume for both partial occlusion and compressed occlusion of the tube. The approximations are validated by testing the RVD of a roller-type peristaltic pump with specified geometries. Validation is achieved by means of measuring the RVD of the physical pump, as well as pump volume displacement over various motor speeds and comparing these values to modeled values. Additionally, the variable occlusion approximation is used to simulate the pressure response of the pump’s inlet and outlet and compared to the same simulation using the measured RVD. The variable occlusion approximation was found to have a normalized root-mean square error (NRMSE) of 6.09% when compared to the experimental average over the entire angle of engagement. Comparing the approximated RVD simulation results to that of the measured RVD simulation results revealed an average NRMSE of 6.35% and 6.62% for the inlet and outlet pressures respectively for the entire span of simulated motor speeds.

Abstract 10535: Tissue-Incubation-Chamber Provides Enhanced Viability of Porcine Aortic Valve Tissue in Dynamic Long-Term Culture

Introduction: Aortic valve (AV) stenosis is caused by fibrosis and calcification of the three-layered valve tissue. Current in vitro and in vivo models are insufficient to reflect cell-cell or cell-matrix interaction and pathophysiological processes. Therefore a novel tissue incubation chamber (TIC) enabling dynamic AV-tissue culture in micro-physiological systems (MPS) was designed to improve emulation of the extreme in vivo conditions of the cardiac cycle. This pilot study aims to verify tissue viability to ensure applicability of the TIC in conjunction with a MPS in AV research. Methods: Porcine AV tissue of 3x5 mm is maintained in the TIC for 14 days within a conventional cell incubator under sterile conditions. A pump-chip able to generate a pulsatile flow rate of 13.4 μl/s (150 bpm) accomplishes average shear forces of 0.017 dyn/cm 2 . Two viability assays were performed to compare dynamic and static setups. AV samples were snap frozen, cryo sectioned and intracellular LDH activity in central tissue regions was visualized using a Tetrazolium-based dye. In addition, a Resazurin reduction assay (50-300 μM) was applied. Results: The LDH-viability stain reveals no significant reduction of viable tissue sections in dynamically incubated AV tissues (96.4 ± 1.3 %) but a significant decrease in the static counterparts (67.8 ± 4.7 %, n=3). The Resazurin assay on the other hand showed significant viability reduction in dynamic setup after 12 days (57 ± 5.4 %), whereas significant reduction was already detected in static culture after 8 days (57.5 ± 15.1 %, n=4). Due to the discrepancy of both viability assays, an inadequate diffusion rate based on structural AV tissue integrity was hypothesized with the need to adapt Resazurin assay concentration. A saturation curve conducted consecutively determined an optimal Resazurin concentration of 300μM to be used in upcoming AV tissue culture (n=4). Conclusion: Enhanced viability of porcine AV tissue following dynamic incubation in the TIC was achieved but further adaptation in terms of higher shear forces and a more physiological sample fixation is envisioned. Dynamically cultured AV tissue cultures in the novel TICs offer a relevant improvement for investigation of AV pathophysiology.

Establishment of a resazurin-based aortic valve tissue viability assay for dynamic culture in a microphysiological system.

Tissue pathogenesis of aortic valve (AV) stenosis is research focus in cardiac surgery. Model limitations of conventional 2D culture of human or porcine valvular interstitial/endothelial cells (VIC/VECs) isolated from aortic valve tissues but also limited ability of (small) animal models to reflect human (patho)physiological situation in AV position raise the need to establish an in vitro setup using AV tissues. Resulting aim is to approximate (patho)physiological conditions in a dynamic pulsatile Microphysiological System (MPS) to culture human and porcine AV tissue with preservation of tissue viability but also defined ECM composition. A tissue incubation chamber (TIC) was designed to implement human or porcine tissues (3×5 mm2) in a dynamic pulsatile culture in conventional cell culture ambience in a MPS. Cell viability assays based on lactate dehydrogenase (LDH)-release or resazurin-conversion were tested for applicability in the system and applied for a culture period of 14 days with interval evaluation of tissue viability on every other day. Resazurin-assay setup was compared in static vs. dynamic culture using varying substance saturation settings (50-300μM), incubation times and tissue masses and was consequently adapted. Sterile dynamic culture of human and porcine AV tissue segments was established at a pulsatile flow rate range of 0.9-13.4μl/s. Implementation of tissues was realized by stitching the material in a thermoplastic polyurethane (TPU)-ring and insertion in the TIC-MPS-system. Culture volume of 2 ml caused LDH dilution not detectable in standard membrane integrity assay setup. Therefore, detection of resazurin-conversion of viable tissue was investigated. Optimal incubation time for viability conversion was determined at two hours at a saturated concentration of 300μM resazurin. Measurement in static conditions was shown to offer comparable results as dynamic condition but allowing optimal handling and TIC sterilization protocols for long term culture. Preliminary results revealed favourable porcine AV tissue viability over a 14 day period confirmed via resazurin-assay comparing statically cultured tissue counterparts. Human and porcine AV tissue can be dynamically cultured in a TIC-MPS with monitoring of tissue viability using an adapted resazurin-assay setup. Preliminary results reveal advantageous viability of porcine AV tissues after dynamic TIC-MPS culture compared to static control.

Modelling the pulsatile flow rate and pressure response of a roller-type peristaltic pump

The unique working mechanics of roller-type peristaltic pumps have allowed their applications to span a wide variety of sectors and industries. The roller-type pump's accurate dosing and hydrostatic capabilities can theoretically allow for the pump to be used for hydraulic actuation (as an electro-hydrostatic actuator) for low pressure applications. This however requires accurate control of the peristaltic pump and its flow rate. The associated pressure pulsations will also have an impact on the pump's selection criteria. Accurate control of roller-type peristaltic pumps commonly rely on flow-meters, which increases the cost of the pump and can complicate control strategies. Current modelling approaches either do not rely on first principle modelling and require expensive simulation software, or do not apply for larger Reynolds numbers at larger flow rates. The most applicable model focusses on the flow rate for each roller individually. This implies that the model requires alterations in order to accommodate pumps with varying numbers of rollers. This paper presents an alternative modelling methodology towards the volume flow rate, pulsatile flow rate qualities, and pressure pulsations commonly found in peristaltic pumps. The model instead focusses on the flow rate at the inlet and the outlet of the pump, rather than on each individual roller. This model is highly scalable and allows for varying number of rollers. The model is validated using a 3D printed peristaltic pump and pulsatile flow rate test bench. The pump is capable of accommodating roller housings with varying numbers of rollers (3 or 2) in order to validate the model.

Boundary conditions investigation to improve computer simulation of cerebrospinal fluid dynamics in hydrocephalus patients

Three-D head geometrical models of eight healthy subjects and 11 hydrocephalus patients were built using their CINE phase-contrast MRI data and used for computer simulations under three different inlet/outlet boundary conditions (BCs). The maximum cerebrospinal fluid (CSF) pressure and the ventricular system volume were more effective and accurate than the other parameters in evaluating the patients’ conditions. In constant CSF pressure, the computational patient models were 18.5% more sensitive to CSF volume changes in the ventricular system under BC “C”. Pulsatile CSF flow rate diagrams were used for inlet and outlet BCs of BC “C”. BC “C” was suggested to evaluate the intracranial compliance of the hydrocephalus patients. The results suggested using the computational fluid dynamic (CFD) method and the fully coupled fluid-structure interaction (FSI) method for the CSF dynamic analysis in patients with external and internal hydrocephalus, respectively.

Modeling of aortic valve stenosis using fluid-structure interaction method.

Fluid structure interaction (FSI) is defined as interaction of the structures with contacting fluids. The aortic valve experiences the interaction with blood flow in systolic phase. In this study, we have tried to predict the hemodynamics of blood flow through a normal and stenotic aortic valve in two relaxation and exercise conditions using a three-dimensional FSI method. The aorta valve was modeled as a three-dimensional geometry including a normal model and two others with 25% and 50% stenosis. The geometry of the aortic valve was extracted from CT images and the models were generated by MMIMCS software and then they were implemented in ANSYS software. The pulsatile flow rate was used for all cases and the numerical simulations were conducted based on a time-dependent domain. The obtained results including the velocity, pressure, and shear stress contours in different systolic time sequences were explained and discussed. The maximum blood flow velocity in relaxation phase was obtained 1.62 m/s (normal valve), 3.78 m/s (25% stenosed valve), and 4.73 m/s (50% stenosed valve). In exercise condition, the maximum velocities are 2.86, 4.32, and 5.42 m/s respectively. The maximum blood pressure in relaxation phase was calculated 111.45 mmHg (normal), 148.66 mmHg (25% stenosed), and 164.21 mmHg (50% stenosed). However, the calculated values in exercise situation were 129.57, 163.58, and 191.26 mmHg.The validation of the predicted results was also conducted using existing literature. We believe that such model are useful tools for biomechanical experts. The further studies should be done using experimental data and the data are implemented on the boundary conditions for better comparison of the results.

Performance characteristics of high-frequency percussive ventilation under hyperbaric conditions

Introduction: Safe administration of critical care hyperbaric medicine requires specialized equipment and advanced training. Equipment must be tested in order to evaluate function in the hyperbaric environment. High-frequency percussive ventilation (HFPV) has been used in intensive care settings effectively, but it has never been tested in a hyperbaric chamber. Methods: Following a modified U.S. Navy testing protocol used to evaluate hyperbaric ventilators, we evaluated an HFPV transport ventilator in a multiplace hyperbaric chamber at 1.0, 1.9, and 2.8 atmospheres absolute (ATA). We used a test lung with analytical software for data collection. The ventilator uses simultaneous cyclic pressure-controlled ventilation at a pulsatile flow rate (PFR)/oscillatory continuous positive airway pressure (oCPAP) ratio of 30/10 with a high-frequency oscillation percussive rate of 500 beats per minute. Inspiratory and expiratory times were maintained at two seconds throughout each breathing cycle. Results: During manned studies, the PFR/oCPAP ratios were 26/6, 22/7, and 22.5/8 at an airway resistance of 20cm H2O/L/second and 18/9, 15.2/8.5, and 13.6/7 at an airway resistance of 50 cm/H2O/L/second at 1, 1.9, and 2.8 ATA. The resulting release volumes were 800, 547, and 513 mL at airway resistance of 20 cm H2O/L/sec and 400, 253, and 180 mL at airway resistance of 50 cm/H2O/L/sec at 1, 1.9, and 2.8 ATA. Unmanned testing showed similar changes. The mean airway pressure (MAP) remained stable throughout all test conditions; theoretically, supporting adequate lung recruitment and gas exchange. A case where HFPV was used to treat a patient for CO poisoning was presented to illustrate that HFPV worked well under HBO2 conditions and no complications occurred during HBO2 treatment. Conclusion: The HFPV transport ventilator performed adequately under hyperbaric conditions and should be considered a viable option for hyperbaric critical care. This ventilator has atypical terminology and produces unique pulmonary physiology, thus requiring specialized training prior to use.

Contribution of atherosclerotic plaque location and severity to the near-wall hemodynamics of the carotid bifurcation: an experimental study and FSI modeling.

Atherosclerosis is initiated by endothelial injury that is related to abnormal values of hemodynamic parameters such as wall shear stress (WSS), oscillatory shear index (OSI) and stress phase angle (SPA), which are more common in arterial bifurcations due to the complex structure. An experimental model of human carotid bifurcation with accurate geometrical and mechanical features was set up, and using realistic pulsatile flow rates, the inlet and outlet pressure pulses were measured for normal and stenosed models with 40% and 80% severities at common carotid (CCA), internal carotid (ICA) and external carotid (ECA) arteries. Based on the obtained experimental data, fluid-structure models were developed to obtain WSS, OSI, and SPA and evaluate pathological consequences at different locations. Mild severity had minor impact, however, inducing severe 80% stenosis in each branch led to considerable localized changes of hemodynamic parameters both in the stenosis site and other locations. This included sharp increases in WSS values accompanied by very low values close to zero before and after the peaks. Severe stenosis not only caused significant changes in the local artery, but also in other branches. OSI and SPA were less sensitive to stenosis, although high peaks were observed on bifurcation site for the stenosis at ECA. The interconnection of arteries at carotid bifurcation results in altered pressure/flow patterns in all branches when a stenosis is applied in any site. Such effect confirms pathological findings that atherosclerotic plaques are observed simultaneously in different carotid branches, although with different degrees of plaque growth and severity.

Hydrogel-based 3D bioprints repair rat small intestine injuries and integrate into native intestinal tissue.

3D Printing has become a mainstay of industry, with several applications in the medical field. One area that could benefit from 3D printing is intestinal failure due to injury or genetic malformations. We bioprinted cylindrical tubes from rat vascular cells that were sized to form biopatches. 2 mm enterotomies were made in the small intestine of male Sprague-Dawley rats, and sealed with biopatches. These intestinal segments were connected to an ex vivo perfusion device that provided independent extraluminal and intraluminal perfusion. The fluorescence signal of fluorescein isothiocyanate (FITC)-inulin in the intraluminal perfusate, a non-absorbable fluorescent marker of intestinal integrity, was measured every 15 min over 90 min, and used to assess the integrity of the segments under both continuous perfusion and alternate-flow perfusion. Enterotomies were made an inch away from the ileocecal junction in male Wistar rats and sealed with biopatches. The animals were monitored daily and euthanized at post-operative days 7, 14, 21, and 30. Blinded histopathological analysis was conducted to compare the patch segments to native intestine. Biopatch-sealed intestinal segments withstood both continuous and pulsatile flow rates without leakage of FITC-inulin above the control baseline. 21 of 26 animals survived with normal activity, weight gain, and stool output. Histopathology of the explanted segments showed progressive villi and crypt formation over the enterotomies, with complete restoration of the epithelium by 30 days. This study presents a novel application of 3D bioprinting to develop a universal repair patch that can seal lesions in vivo, and fully integrate into the native intestine.

Torrents of torment: turbulence as a mechanism of pulsatile tinnitus secondary to venous stenosis revealed by high-fidelity computational fluid dynamics

BackgroundPulsatile tinnitus (PT) is a debilitating condition that can be caused by a vascular abnormality, such as an arterial or venous lesion. Although treatment of PT-related venous lesions has been...

Abstract 17314: Flow-Mediated Susceptibility of Cerebral Endothelia to Sars-CoV-2 Infection Using Endothelialized 3D Human Vascular Models

Introduction: The clinical syndrome associated with Sars-CoV-2 infection is associated with an increased rate of cerebrovascular events, predominantly ischemic stroke. Direct viral invasion of the cerebral endothelium could be a significant driver of Sars-CoV-2-mediated stroke through expression of ACE2 and viral entry co-factors including TMPRSS2. Prior work indicates that ACE2 mRNA and protein are expressed in the endothelial cells of the brain, yet the effect of flow-mediated phenomena on ACE2 expression and the susceptibility of human cerebral endothelia to Sars-CoV-2 infection is unknown. Methods: 3D printed models of the human middle cerebral artery were endothelialized with either human umbilical vein endothelial cells (HUVECs) or human brain microvascular endothelial cells (HBMECs). Endothelialized models were subjected to 3D rotational perfusional culture at variable pulsatile flow rates (0-22.5 dynes/cm 2 ). ACE2 and TMPRSS2 expression were measured by Taqman qPCR. Biotinylated recombinant Sars-CoV-2 S protein was used to judge regional vessel binding of virus using confocal microscopy. Results: In 3D models endothelialized with either HUVECs or HBMECs, ACE2 mRNA expression is significantly modulated by vessel diameter and the presence of of flow (15 dynes/cm 2 ) (p<0.0001 by two-way ANOVA). Pulsatile flow drives ACE2 expression more robustly in HUVECs than in HBMECs (11.5-fold vs. 4.9-fold; p<0.001). Higher flow rates (22.5 dynes/cm 2 ) produced further increases in ACE2 expression in both cell types. Gene expression analysis demonstrated no detection of the Sars-CoV-2 viral entry co-factor TMPRSS2 in HBMECs. Flow-mediated ACE2 expression was associated with binding of recombinant Sars-CoV-2 S protein to the vessel wall suggesting direct cerebrovascular susceptibility to Sars-CoV-2. Conclusion: The Sars-CoV-2 cellular receptor ACE2 is expressed by human cerebral endothelia in a flow-dependent manner. Cerebral vessels are susceptible to Sars-CoV-2 infection and bind viral S protein under flow conditions but likely requires unique co-factors for viral entry. Identification of the molecular mechanisms triggered by Sars-CoV-2 infection in brain vasculature can alleviate the burden of stroke associated with COVID-19.