Blood Analog Research Articles

In Vitro Characterization of the Pittsburgh Pediatric Ambulatory Lung.

Acute and chronic respiratory failure are a significant source of pediatric morbidity and mortality. Current respiratory support options used to bridge children to lung recovery or transplantation typically render them bedridden and can worsen long-term patient outcomes. The Pittsburgh Pediatric Ambulatory Lung (P-PAL) is a wearable pediatric blood pump and oxygenator (0.3 m surface area) integrated into a single compact unit that enables patient ambulation. The P-PAL is intended for long-term use and designed to provide up to 90% of respiratory support in children weighing 5-25 kg. Computational fluid dynamics and numerical gas exchange modeling were used to design the P-PAL and predict its performance. A P-PAL prototype was then used to obtain pressure versus flow curves at various impeller rotation rates using a blood analog fluid. In vitro oxygen exchange rates were obtained in blood in accordance with ISO standard 7199. The normalized index of hemolysis (NIH) was measured over a 6 hour period at blood flow rates of 1 and 2.5 L/min. The P-PAL provided blood flows of 1-2.5 L/min against the pressure drop associated with its intended-use pediatric cannulas. The oxygen exchange rate reached a maximum of 108 ml/min at a blood flow rate of 2.5 L/min and met our respiratory support design target. Device-induced hemolysis was low with NIH values of 0.022-0.027 g/100 L in the intended blood flow rate range. In conclusion, the current P-PAL design met our pumping, oxygenation, and hemolysis specifications and has the potential to improve treatment for pediatric respiratory failure.

Density and Viscosity Matched Newtonian and non-Newtonian Blood-Analog Solutions with PDMS Refractive Index.

Optical imaging is commonly used to investigate biological flows and cardiovascular disease using compliant silicone polydimethysiloxane (PDMS) Sylgard 184 geometries. However, selecting the working fluid with blood density and viscosity, and PDMS index of refraction (RI) for such experiments is challenging. Currently, water-glycerol is commonly used and sodium iodide (NaI) often added to increase the index of refraction without changing fluid viscosity. But the resulting fluid density is well above blood. Moreover, NaI is expensive, has safety and material discoloration concerns, and has been reported to affect non-Newtonian fluid behavior. Here, we present a new blood analog alternative based on urea. Urea is approximately five to fifteen times less expensive than NaI, safe and easy to handle, optically clear, and causes no discoloration. Water-glycerol-urea solutions, unlike those with NaI, simultaneously matched the density and viscosity of blood and RI of PDMS. Water-xylitol and water-xylitol-urea solutions are also possible blood analog solutions. Xanthan gum (XG)-water-glycerol non-Newtonian solutions maintained similar viscoelastic properties throughout the range of weight percent (about 15-25%) of urea and NaI used here. The results showed that the XG weight percent affected viscoelastic properties more than the weight percent of urea or NaI tested in this study. Overall, we demonstrate urea is useful for PDMS blood analog experiments and should also be considered as an inexpensive additive, and an alternative to NaI.

A Simplified Model for Predicting Friction Factors of Laminar Blood Flow in Small-Caliber Vessels

The aim of this study was to provide scientists with a straightforward correlation that can be applied to the prediction of the Fanning friction factor and consequently the pressure drop that arises during blood flow in small-caliber vessels. Due to the small diameter of the conduit, the Reynolds numbers are low and thus the flow is laminar. This study has been conducted using Computational Fluid Dynamics (CFD) simulations validated with relevant experimental data, acquired using an appropriate experimental setup. The experiments relate to the pressure drop measurement during the flow of a blood analogue that follows the Casson model, i.e., an aqueous Glycerol solution that contains a small amount of Xanthan gum and exhibits similar behavior to blood, in a smooth, stainless steel microtube (L = 50 mm and D = 400 μm). The interpretation of the resulting numerical data led to the proposal of a simplified model that incorporates the effect of the blood flow rate, the hematocrit value (35–55%) and the vessel diameter (300–1800 μm) and predicts, with better than ±10% accuracy, the Fanning friction factor and consequently the pressure drop during laminar blood flow in healthy small-caliber vessels.

Inter-Laboratory Characterization of the Velocity Field in the FDA Blood Pump Model Using Particle Image Velocimetry (PIV).

A credible computational fluid dynamics (CFD) model can play a meaningful role in evaluating the safety and performance of medical devices. A key step towards establishing model credibility is to first validate CFD models with benchmark experimental datasets to minimize model-form errors before applying the credibility assessment process to more complex medical devices. However, validation studies to establish benchmark datasets can be cost prohibitive and difficult to perform. The goal of this initiative sponsored by the U.S. Food and Drug Administration is to generate validation data for a simplified centrifugal pump that mimics blood flow characteristics commonly observed in ventricular assist devices. The centrifugal blood pump model was made from clear acrylic and included an impeller, with four equally spaced, straight blades, supported by mechanical bearings. Particle Image Velocimetry (PIV) measurements were performed at several locations throughout the pump by three independent laboratories. A standard protocol was developed for the experiments to ensure that the flow conditions were comparable and to minimize systematic errors during PIV image acquisition and processing. Velocity fields were extracted at the pump entrance, blade passage area, back gap region, and at the outlet diffuser regions. A Newtonian blood analog fluid composed of sodium iodide, glycerin, and water was used as the working fluid. Velocity measurements were made for six different pump flow conditions, with the blood-equivalent flow rate ranging between 2.5 and 7 L/min for pump speeds of 2500 and 3500rpm. Mean intra- and inter-laboratory variabilities in velocity were ~ 10% at the majority of the measurement locations inside the pump. However, the inter-laboratory variability increased to more than ~ 30% in the exit diffuser region. The variability between the three laboratories for the peak velocity magnitude in the diffuser region ranged from 5 to 25%. The bulk velocity field near the impeller changed proportionally with the rotational speed but was relatively unaffected by the pump flow rate. In contrast, flow in the exit diffuser region was sensitive to both the flow rate and the rotational speed. Specifically, at 3500rpm, the exit jet tilted toward the inner wall of the diffuser at a flow rate of 2.5 L/min, but the jet tilted towards the outer wall when the flow rate was 7 L/min. Inter-laboratory experimental mean velocity data (and the corresponding variance) were obtained for the FDA pump model and are available for download at https://nciphub.org/wiki/FDA_CFD . Experimental datasets from the inter-laboratory characterization of benchmark flow models, including the blood pump model presented herein and our previous nozzle model, can be used for validating future CFD studies and to collaboratively develop guidelines on best practices for verification, validation, uncertainty quantification, and credibility assessment of CFD simulations in the evaluation of medical devices (e.g. ASME V&V 40 standards working group).

Bench Validation of a Compact Low-Flow CO2 Removal Device

BackgroundThere is increasing evidence demonstrating the value of partial extracorporeal CO2 removal (ECCO2R) for the treatment of hypercapnia in patients with acute exacerbations of chronic obstructive pulmonary disease and acute respiratory distress syndrome. Mechanical ventilation has traditionally been used to treat hypercapnia in these patients, however, it has been well-established that aggressive ventilator settings can lead to ventilator-induced lung injury. ECCO2R removes CO2 independently of the lungs and has been used to permit lung protective ventilation to prevent ventilator-induced lung injury, prevent intubation, and aid in ventilator weaning. The Low-Flow Pittsburgh Ambulatory Lung (LF-PAL) is a low-flow ECCO2R device that integrates the fiber bundle (0.65 m2) and centrifugal pump into a compact unit to permit patient ambulation.MethodsA blood analog was used to evaluate the performance of the pump at various impeller rotation rates. In vitro CO2 removal tested under normocapnic conditions and 6-h hemolysis testing were completed using bovine blood. Computational fluid dynamics and a mass-transfer model were also used to evaluate the performance of the LF-PAL.ResultsThe integrated pump was able to generate flows up to 700 mL/min against the Hemolung 15.5 Fr dual lumen catheter. The maximum vCO2 of 105 mL/min was achieved at a blood flow rate of 700 mL/min. The therapeutic index of hemolysis was 0.080 g/(100 min). The normalized index of hemolysis was 0.158 g/(100 L).ConclusionsThe LF-PAL met pumping, CO2 removal, and hemolysis design targets and has the potential to enable ambulation while on ECCO2R.

Flow-induced deformation in a microchannel with a non-Newtonian fluid.

In this work, we have fabricated physiologically relevant polydimethylsiloxane microfluidic phantoms to investigate the fluid-structure interaction that arises from the interaction between a non-Newtonian fluid and the deformable wall. A shear thinning fluid (Xanthan gum solution) is used as the blood analog fluid. We have systematically analyzed the steady flow characteristics of the microfluidic phantom using pressure drop, deformation, and flow visualization using micro-PIV (Particle Image Velocimetry) to identify the intricate aspects of the pressure as well as the velocity field. A simple mathematical formulation is introduced to evaluate the flow induced deformation. These results will aid in the design and development of deformable microfluidic systems and provide a deeper understanding of the fluid-structure interaction in microchannels with special emphasis on biomimetic in-vitro models for lab-on-a-chip applications.

Left heart simulator for evaluation of prosthetic heart valves: behavior of tricuspid bioprosthetic mitral valves during diastole

Abstract The purpose of this work was to know the characteristics of tricuspid bioprosthetic mitral valves in terms of velocity fields and valve aperture areas for some instants concerning the diastole. A left heart simulator was used as an in vitro platform for the bioprostheses. A particle image velocimetry (PIV) system was applied for characterizing instantaneous 2D-velocity fields within the left ventricular model (LVM), and also for detection of mitral bioprostheses aperture areas. The ventricular states were established for 60, 70 and 90 bpm (beats per minute) and a blood analog fluid based on glycerol was employed at 36.5±0.5oC. Two mitral bioprostheses (nominal diameter of 27 and 31 mm) and an aortic bileaflet mechanical valve (27 mm diameter) were used. Instantaneous two-dimensional velocity fields at the upper part of the LVM, for two sections (in the middle of the LVM, and also in a section at 7 mm of distance from that) were obtained. Averaged velocity vector maps (N = 50) were calculated for some instants of interest. According to different heart rates, bioprostheses and sections within the LVM, the velocity fields were presented, as well the bioprostheses aperture areas. In conclusion, the experimental scope including different ventricular states showed how the inflow characteristics of the LVM change according to the chosen variables. This information will aid the validation of a numeric model for the LVM operation, which has been elaborated (some specific methods are presented in the Appendix).

Experimental evaluation of a novel swirling flow generator placed in an artery with a stenosis

It is known that the presence of a stenosis in an artery can result to blood flow separation and to formation of recirculation zones downstream the stenosis. Thus, due to both low wall shear stress (WSS) values and longer residence time, excess cholesterol is deposited on the inner surface of the vessel leading to the development of the atherosclerotic plaque. A swirling-flow generator placed upstream of the stenosis reduces the length of the recirculation zone and consequently the tendency to form atherosclerotic plaque. Initially, in a previous study, using Computational Fluid Dynamics (CFD) and Response Surface Methodology (RSM), the values of the key design parameters corresponding to the optimal design were found. In this study, based on the CFD results, the swirling-flow generator was constructed using a 3D printer and positioned downstream a stenosis in an artery-like vessel. The aim is the validation of the CFD results by experimentally investigating the flow characteristics of a blood analogue downstream the stenosis. The local velocity was measured using the μ-PIV technique. It was found that both the measured pressure values and the calculated wall shear stress values are in very good agreement (less than 10%) with the computational results. Thus, the proposed model can be considered reliable and it could be used for the design and construction of a swirl generating device which can significantly reduce the length of the recirculation zone and eventually the progression of atherosclerosis in a human artery

Experimental investigation of the effect of non-Newtonian behavior of blood flow in the Fontan circulation

The Fontan procedure for univentricular heart defects creates a unique circulation where all pulmonary blood flow is passively supplied directly from systemic veins. Computational simulations, aimed at optimizing the surgery, have assumed blood to be a Newtonian fluid without evaluating the potential error introduced by this assumption. We compared flow behavior between a non-Newtonian blood analog (0.04% xanthan gum) and a control Newtonian fluid (45% glycerol) in a simplified model of the Fontan circulation. Particle image velocimetry was used to examine flow behavior at two different cardiac outputs and two caval blood flow distributions. Pressure and flow rates were measured at each inlet and outlet. Velocity, shear strain, and shear stress maps were derived from velocity data. Power loss was calculated from pressure, flow, and velocity data. Power loss was increased in all test conditions with xanthan gum vs. glycerol (mean 10 ± 2.9% vs. 5.6 ± 1.3%, p=0.032). Pulmonary blood flow distribution differed in all conditions, more so at low cardiac output. Caval blood flow mixing patterns and shear stress were also qualitatively different between the solutions in all conditions. We conclude that assuming blood to be a Newtonian fluid introduces considerable error into simulations of the Fontan circulation, where low-shear flow predominates.

Application of a screening method for fentanyl and its analogues using UHPLC-QTOF-MS with data-independent acquisition (DIA) in MSE mode and retrospective analysis of authentic forensic blood samples.

The steady appearance of new fentanyl analogues and the associated overdose deaths require the development of sensitive screening approaches to detect these compounds in biological samples and seizures. We developed a targeted screening method to detect 50 4-anilidopiperidine-related fentanyl analogues in whole blood using ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry in data-independent acquisition mode. Sample preparation was performed using protein precipitation on a fully automated robotic setup. Thirteen analogues were selected to validate the method. A small matrix ion enhancement effect (110-123%) was observed for all of the compounds; the recovery ranged from 67% to 81% and the process efficiency from 81% to 98%. Limit of detection was within 0.0005-0.001mg/kg and limit of identification ranged from 0.001 to 0.005mg/kg. In the retrospective analysis of 2339 forensic blood samples, the major finding was fentanyl (n=56), followed by alfentanil (n=5) and remifentanil (n=1). Identification of 34 fentanyl analogues was based on the predicted product ions resulting from common fentanyl-specific collision-induced cleavages, particularly on the product ion result of the fragmentation on the C-N bond between the phenylamide moiety and the piperidine ring. The proposed hypothesis was supported by the targeted analysis of 16 fentanyl analogues using this method and available published mass spectral data sources for fentanyl analogues. A targeted screening method for 50 fentanyl analogues was successfully validated and implemented to analyse authentic blood samples, where identifying targeted fentanyl analogues was tentatively achieved without using reference standards.

Exposure to seismic air gun signals causes physiological harm and alters behavior in the scallop Pecten fumatus

Seismic surveys map the seabed using intense, low-frequency sound signals that penetrate kilometers into the Earth's crust. Little is known regarding how invertebrates, including economically and ecologically important bivalves, are affected by exposure to seismic signals. In a series of field-based experiments, we investigate the impact of exposure to seismic surveys on scallops, using measurements of physiological and behavioral parameters to determine whether exposure may cause mass mortality or result in other sublethal effects. Exposure to seismic signals was found to significantly increase mortality, particularly over a chronic (months postexposure) time scale, though not beyond naturally occurring rates of mortality. Exposure did not elicit energetically expensive behaviors, but scallops showed significant changes in behavioral patterns during exposure, through a reduction in classic behaviors and demonstration of a nonclassic "flinch" response to air gun signals. Furthermore, scallops showed persistent alterations in recessing reflex behavior following exposure, with the rate of recessing increasing with repeated exposure. Hemolymph (blood analog) physiology showed a compromised capacity for homeostasis and potential immunodeficiency, as a range of hemolymph biochemistry parameters were altered and the density of circulating hemocytes (blood cell analog) was significantly reduced, with effects observed over acute (hours to days) and chronic (months) scales. The size of the air gun had no effect, but repeated exposure intensified responses. We postulate that the observed impacts resulted from high seabed ground accelerations driven by the air gun signal. Given the scope of physiological disruption, we conclude that seismic exposure can harm scallops.

Effect of meal size and texture on gastric pouch emptying and glucagon-like peptide 1 after gastric bypass surgery

BackgroundRoux-en-Y gastric bypass (RYGB) accelerates gastric pouch emptying, enhances postprandial glucagon-like peptide 1 (GLP-1) and insulin, and lowers glucose concentrations. To prevent discomfort and reactive hypoglycemia, it is recommended that post-RYGB patients eat small, frequent meals and avoid caloric drinks. However, the effect of meal size and texture on GLP-1 and metabolic response has not been studied. ObjectivesTo demonstrate that frequent minimeals and solid meals (S) elicit less GLP-1 and insulin release and less reactive hypoglycemia and are better tolerated compared with a single isocaloric liquid meal (L). SettingA university hospital. MethodsIn this prospective study, 32 RYGB candidates were enrolled and randomized to L or S groups before gastric bypass. Each subject received an L or S 600-kcal single meal (SM) administered at hour 0 or three 200-kcal minimeals administered at hours 0, 2, and 4 on 2 separate days. Twenty-one patients were retested 1 year after RYGB. Blood and visual analogue scale measurements were collected up to 6 hours postprandially. Outcome measures included gastric pouch emptying, glucose, insulin, and GLP-1; hunger, fullness, and stomach discomfort were measured by visual analogue scale. ResultsTwenty-one were patients retested after RYGB (L: n = 12; S: n = 9). Meal texture had a significant effect on peak GLP-1 (L-SM: 106.1 ± 67.2 versus S-SM: 45.3 ± 25.2 pM, P = .004), peak insulin, and postprandial glucose. Hypoglycemia was more frequent after the L-SM meal compared with the S-SM. Gastric pouch emptying was 2.4 times faster after RYGB but was not affected by texture. ConclusionsMeal texture and size have significant impact on tolerance and metabolic response after RYGB.

In vitro particulate analogue fluids for experimental studies of rheological and hemorheological behavior of glucose-rich RBC suspensions.

Suspensions of healthy and pathological red blood cells (RBC) flowing in microfluidic devices are frequently used to perform in vitro blood experiments for a better understanding of human microcirculation hemodynamic phenomena. This work reports the development of particulate viscoelastic analogue fluids able to mimic the rheological and hemorheological behavior of pathological RBC suspensions flowing in microfluidic systems. The pathological RBCs were obtained by an incubation of healthy RBCs at a high concentration of glucose, representing the pathological stage of hyperglycaemia in diabetic complications, and analyses of their deformability and aggregation were carried out. Overall, the developed in vitro analogue fluids were composed of a suspension of semi-rigid microbeads in a carrier viscoelastic fluid made of dextran 40 and xanthan gum. All suspensions of healthy and pathological RBCs, as well as their particulate analogue fluids, were extensively characterized in steady shear flow, as well as in small and large amplitude oscillatory shear flow. In addition, the well-known cell-free layer (CFL) phenomenon occurring in microchannels was investigated in detail to provide comparisons between healthy and pathological in vitro RBC suspensions and their corresponding analogue fluids at different volume concentrations (5% and 20%). The experimental results have shown a similar rheological behavior between the samples containing a suspension of pathological RBCs and the proposed analogue fluids. Moreover, this work shows that the particulate in vitro analogue fluids used have the ability to mimic well the CFL phenomenon occurring downstream of a microchannel contraction for pathological RBC suspensions. The proposed particulate fluids provide a more realistic behavior of the flow properties of suspended RBCs when compared with existing non-particulate blood analogues, and consequently, they are advantageous for detailed investigations of microcirculation.

Canthal cutdown for emergent treatment of orbital compartment syndrome

ABSTRACTThis article evaluates the use of a “canthal cutdown” technique in orbital compartment syndrome in a cadaveric model. Twelve cadaver orbits were used to simulate orbital compartment syndrome using a blood analog solution. Two pressure probes, in different orbital locations, were used to monitor orbital pressure. Pressure was monitored during successive procedures: canthotomy, cantholysis, and canthal cutdown. Orbits were then re-injected with solution, simulating an active orbital hemorrhage, and pressure measurements were recorded over a 10-minute duration. No statistically significant difference was found between the two orbital pressure monitoring devices at each measurement point (p = 0.99). Significant pressure reductions, for both probes, were observed after canthal cutdown compared to initial measurement after injection of 20 mL blood analog (p < 0.001 and p = 0.005). When comparing the orbital pressure following canthotomy and inferior cantholysis versus canthal cutdown, the cutdown procedure provided an additional 74% in orbital pressure reduction (p =0.01). After re-injection of 10 mL of solution and 10 minutes of egress, pressure returned to baseline (probe 1: baseline 7 mm Hg vs. post-cutdown at 10 minutes 7 mm Hg; p = 0.83; and probe 2: 5 mm Hg vs. 5 mm Hg; p = 0.83). The canthal cutdown technique provides further reduction in orbital pressure versus canthotomy and cantholysis alone. The technique may be effective for treatment of static orbital compartment syndrome and temporizing treatment of compartment syndrome from active orbital hemorrhages.

An LC-MS-MS Method for the Analysis of Carfentanil, 3-Methylfentanyl, 2-Furanyl Fentanyl, Acetyl Fentanyl, Fentanyl and Norfentanyl in Postmortem and Impaired-Driving Cases.

In July of 2016, carfentanil (CF) emerged in Northeast Ohio resulting in over 25 deaths within a 30-day period. A total of 125 deaths have occurred in Summit County and Cuyahoga County has reported 40 deaths, relating to the presence of CF either alone, or in combinations with heroin and fentanyl. Prior to this surge in CF cases, positive fentanyl enzyme-linked immunosorbent assay (ELISA) screening results were increasing in number. Many were negative for fentanyl confirmation by gas chromatography-mass spectrometry. Fentanyl analogs such as CF, acetyl fentanyl (AF), 2-furanyl fentanyl (2-Fu-F) and 3-methylfentanyl (3-MF) may be present in these cases. Some fentanyl analogs like CF and 3-MF do not cross-react with the Immunalysis ELISA fentanyl assay. With the emergence of potent synthetic fentanyl analogs, questions arose as to how to interpret their very low concentrations or absence in the blood in relation to cause of death. Driving under the influence of drugs (DUID) blood specimens had also tested positive for CF by reference laboratories. A liquid chromatography-tandem mass spectrometry method was developed to identify and quantify fentanyl, norfentanyl (NF) and four analogs: AF, 2-Fu-F, 3-MF and CF. The method has been utilized to quantify these fentanyl analogs in blood and vitreous humor in authentic antemortem and postmortem cases. Calibration curves were established between 0.10-4.0 ng/mL (NF, AF, 3-MF, 2-Fu-F and CF) and 1.0-40 ng/mL for fentanyl. In total, 98 postmortem cases analyzed produced the following blood concentration ranges: CF (0.11-0.88 ng/mL), 3-MF (0.15-1.7 ng/mL), 2-Fu-F (0.15-0.30 ng/mL), AF (0.14-0.16 ng/mL), fentanyl (1.1-15 ng/mL) and NF (0.10-3.7 ng/mL). Only CF, fentanyl and NF were detected in a statistically significant subset DUID population of 26 cases producing concentration ranges between 0.11 and 0.47 ng/mL, 1.0 and 9.8 ng/mL, and 0.11 and 3.5 ng/mL, respectively.

Detection and quantification of 12 anabolic steroids and analogs in human whole blood and 20 in hair using LC-HRMS/MS: application to real cases.

We developed and validated a method to detect and quantify 12 anabolic steroids in blood (androstenedione, dihydrotestosterone, boldenone, epitestosterone, mesterolone, methandienone, nandrolone, stanozolol, norandrostenedione, tamoxifene, testosterone, trenbolone) and eight more in hair samples (nandrolone phenylpropionate, nandrolone decanoate, testosterone propionate, testosterone benzoate, testosterone cypionate, testosterone decanoate, testosterone phenylpropionate, testosterone undecanoate) using liquid chromatography coupled to high-resolution mass spectrometry. This method used a benchtop Orbitrap mass spectrometer operating with an APCI probe under positive ionization mode. Analysis was realized in full scan experiment with a nominal resolving power of 140,000. After addition of the internal standard (testosterone-D3) and incubation in phosphate buffer pH=5 for hair, 200μL of blood and 30mg of hair samples were extracted with heptane. LOQ and LOD were determined at 5 and 1ngmL-1 in whole blood and 10 to 100pgmg-1 and 2 to 20pgmg-1 in hair according to the compounds, respectively. The method was linear in the 5-1000ngmL-1 range in whole blood and between 10 or 100pgmg-1 and 1000pgmg-1 in hair with correlation coefficients >0.99, and intra- and inter-day accuracy and precision were <14.8% for all compounds except for some esters in hairs (<19.9%) probably due to an important matrix effect for these compounds. This sensitive and specific method to detect anabolic steroids has been successfully applied to two real cases, for which various anabolic steroids in whole blood, urine, and hair were identified and quantified.

Hemodynamic Performance of a Novel Right Ventricular Assist Device (PERKAT).

Acute right ventricular failure (RVF) is an increasing clinical problem and a life-threatening condition. Right ventricular assist devices represent a reasonable treatment option for patients with refractory RVF. We here present a novel percutaneously implantable device for right ventricular support. The PERKAT device is based on a nitinol stent cage, which is covered with valve-carrying foils. A flexible outlet trunk with a pigtail tip is connected to the distal part. The device is driven by an intra-aortic balloon pump (IABP) drive unit, which inflates/deflates a standard IABP-balloon placed within the stent cage. In-vitro evaluation was done in a liquid bath containing water or blood analog. The PERKAT device was tested in different afterload settings using two different IABP-balloons and varying inflation/deflation rates. We detected flow rates ranging from 1.97 to 3.93 L/min depending on the afterload setting, inflation/deflation rate, balloon size, and the medium used. Flow rates between water and blood analog were nearly comparable, and in the higher inflation/deflation rate settings slightly higher with water. Based on this promising in vitro data, the innovative percutaneously implantable PERKAT device has a potential to become a therapeutic option for patients with RVF refractory to medical treatment.

Mathematical Modeling of Rotary Blood Pumps in a Pulsatile In Vitro Flow Environment.

Nowadays, sacrificing animals to develop medical devices and receive regulatory approval has become more common, which increases ethical concerns. Although in vivo tests are necessary for development and evaluation of new devices, nonetheless, with appropriate in vitro setups and mathematical models, a part of the validation process can be performed using these models to reduce the number of sacrificed animals. The main aim of this study is to present a mathematical model simulating the hydrodynamic function of a rotary blood pump (RBP) in a pulsatile in vitro flow environment. This model relates the pressure head of the RBP to the flow rate, rotational speed, and time derivatives of flow rate and rotational speed. To identify the model parameters, an in vitro setup was constructed consisting of a piston pump, a compliance chamber, a throttle, a buffer reservoir, and the CentriMag RBP. A 40% glycerin-water mixture as a blood analog fluid and deionized water were used in the hydraulic circuit to investigate the effect of viscosity and density of the working fluid on the model parameters. First, model variables were physically measured and digitally acquired. Second, an identification algorithm based on regression analysis was used to derive the model parameters. Third, the completed model was validated with a totally different set of in vitro data. The model is usable for both mathematical simulations of the interaction between the pump and heart and indirect pressure measurement in a clinical context.

Pulsatile flow in a compliant stenosed asymmetric model

Time-varying velocity field in an asymmetric constricted tube is experimentally studied using a two-dimensional particle image velocimetry system. The geometry resembles a vascular disease which is characterized by arterial narrowing due to plaque deposition. The present study compares the nature of flow patterns in rigid and compliant asymmetric constricted tubes for a range of dimensionless parameters appearing in a human artery. A blood analogue fluid is employed along with a pump that mimics cardioflow conditions. The peak Reynolds number range is Re ~ 300–800, while the Womersley number range considered in experiments is Wo ~ 6–8. These values are based on the peak velocity in a straight rigid tube connected to the model, over a pulsation frequency range of 1.2–2.4 Hz. The medial-plane velocity distribution is used to investigate the nature of flow patterns. Temporal distribution of stream traces and hemodynamic factors including WSS, TAWSS and OSI at important phases of the pulsation cycle are discussed. The flow patterns obtained from PIV are compared to a limited extent against numerical simulation. Results show that the region downstream of the constriction is characterized by a high-velocity jet at the throat, while a recirculation zone, attached to the wall, evolves in time. Compliant models reveal large flow disturbances upstream during the retrograde flow. Wall shear stress values are lower in a compliant model as compared to the rigid. Cross-plane flow structures normal to the main flow direction are visible at select phases of the cycle. Positive values of largest Lyapunov exponent are realized for wall movement and are indicative of chaotic motion transferred from the flow to the wall. These exponents increase with Reynolds number as well as compliance. Period doubling is observed in wall displacement of highly compliant models, indicating possible triggering of hemodynamic events in a real artery that may cause fissure in the plaque deposits.

Long-term durability test of axial-flow ventricular assist device under pulsatile flow.

A long-term durability test was conducted on a newly developed axial-flow ventricular assist device (VAD) with hydrodynamic bearings. The mock circulatory loop consisted of a diaphragm pump with a mechanical heart valve, a reservoir, a compliance tank, a resistance valve, and flow paths made of polymer or titanium. The VAD was installed behind the diaphragm pump. The blood analog fluid was a saline solution with added glycerin at a temperature of 37°C. A pulsatile flow was introduced into the VAD over a range of flow rates to realize a positive flow rate and a positive pressure head at a given impeller rotational speed, yielding a flow rate of 5L/min and a pressure of 100mmHg. Pulsatile flow conditions were achieved with the diastolic and systolic flow rates of ~0 and 9.5L/min, respectively, and an average flow rate of ~5L/min at a pulse rate of 72bpm. The VAD operation was judged by not only the rotational speed of the impeller, but also the diastolic, systolic, and average flow rates and the average pressure head of the VAD. The conditions of the mock circulatory loop, including the pulse rate of the diaphragm pump, the fluid temperature, and the fluid viscosity were maintained. Eight VADs were tested with testing periods of 2years, during which they were continuously in operation. The VAD performance factors, including the power consumption and the vibration characteristics, were kept almost constant. The long-term durability of the developed VAD was successfully demonstrated.