In-Vitro Validation of Self-Powered Fontan Circulation for Treatment of Single Ventricle Anomaly

Around 8% of all newborns with a Congenital Heart Defect (CHD) have only a single functioning ventricle. The Fontan operation has served as palliation for this anomaly for decades, but the surgery entails multiple complications, and the survival rate is less than 50% by adulthood. A rapidly testable novel alternative is proposed by creating a bifurcating graft, or Injection Jet Shunt (IJS), used to “entrain” the pulmonary flow and thus provide assistance while reducing the caval pressure. A dynamically scaled Mock Flow Loop (MFL) has been configured to validate this hypothesis. Three IJS nozzles of varying diameters 2, 3, and 4 mm with three aortic anastomosis angles and pulmonary vascular resistance (PVR) reduction have been tested to validate the hypothesis and optimize the caval pressure reduction. The MFL is based on a Lumped-Parameter Model (LPM) of a non-fenestrated Fontan circulation. The best outcome was achieved with the experimental testing of a 3 mm IJS by producing an average caval pressure reduction of more than 5 mmHg while maintaining the clinically acceptable pulmonary flow rate (Qp) to systemic flow rate (Qs) ratio of ~1.5. Furthermore, alteration of the PVR helped in achieving higher caval pressure reduction with the 3 mm IJS at the expense of an increase in Qp/Qs ratio.

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Inflation-associated increases in lung polyamine uptake: role of altered pulmonary vascular flow

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1989.257.5.e729 ◽

1989 ◽

Vol 257 (5) ◽

pp. E729-E735 ◽

Cited By ~ 2

Author(s):

H. W. Karl ◽

L. A. Russo ◽

D. E. Rannels

Keyword(s):

Flow Rate ◽

Metabolic Response ◽

Left Lung ◽

Pulmonary Flow ◽

Vascular Flow ◽

Isolated Lung ◽

Wide Range ◽

Camp Metabolism ◽

The Right

Unilateral pneumonectomy in rats leads to rapid compensatory growth of the remaining lung. Previous studies showed that postoperative increases in lung mass are preceded by enhanced uptake of exogenous polyamines and by alterations in adenosine 3',5'-cyclic monophosphate (cAMP) metabolism. These effects are both mimicked in lungs of intact animals subjected to increased inflation in vitro. Partial pneumonectomy also leads to increased flow to the contralateral lung associated with reduced pulmonary vascular resistance. This raises the possibility that the postoperative metabolic response is initiated by changes in pulmonary artery pressure (Pa) or flow, rather than altered inflation. The present studies were designed to investigate this issue. Uptake of exogenous [14C]spermidine by isolated perfused rat lungs was examined over a wide range (greater than 4-fold) of pulmonary flow and ventilation at fixed PaS. Assessment of tissue metabolism from rates of protein synthesis suggested stability of the isolated lung preparations. Apnea (0 ventilation) had no effect on spermidine uptake or flow rate, compared with lungs evaluated under normal conditions of ventilation (inspiratory pressure, 15 cmH2O; positive end expiratory pressure, 2 cmH2O; rate, 70 breaths/min). At both high and low Pa (at a flow rate of 37 +/- 1 and 11 +/- 2 ml/min, respectively, with 0 ventilation), removal of the left lung from the perfusion circuit increased specific right lung flow rate greater than 30% but had no effect on spermidine uptake. Similar alterations in flow rate to the right or both apneic lungs had no effect on the tissue content of cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)

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Computational Fontan Analysis: Preserving accuracy while expediting workflow

10.1101/2021.10.28.466272 ◽

2021 ◽

Author(s):

Xiaolong Liu ◽

Seda Aslan ◽

Byeol Kim ◽

Linnea Warburton ◽

Derrick Jackson ◽

...

Keyword(s):

Particle Filtering ◽

Cfd Simulation ◽

Fontan Operation ◽

Flow Distribution ◽

Mesh Size ◽

Computational Time ◽

Patient Specific ◽

Flow Loop ◽

Cfd Simulations

Background: Post-operative outcomes of the Fontan operation have been linked to graft shape after implantation. Computational fluid dynamics (CFD) simulations are used to explore different surgical options. The objective of this study is to perform a systematic in vitro validation for investigating the accuracy and efficiency of CFD simulation to predict Fontan hemodynamics. Methods: CFD simulations were performed to measure indexed power loss (iPL) and hepatic flow distribution (HFD) in 10 patient-specific Fontan models, with varying mesh and numerical solvers. The results were compared with a novel in vitro flow loop setup with 3D printed Fontan models. A high-resolution differential pressure sensor was used to measure the pressure drop for validating iPL predictions. Microparticles with particle filtering system were used to measure HFD. The computational time was measured for a representative Fontan model with different mesh sizes and numerical solvers. Results: When compared to in vitro setup, variations in CFD mesh sizes had significant effect on HFD (p = 0.0002) but no significant impact on iPL (p = 0.069). Numerical solvers had no significant impact in both iPL (p = 0.50) and HFD (P = 0.55). A transient solver with 0.5 mm mesh size requires computational time 100 times more than a steady solver with 2.5 mm mesh size to generate similar results. Conclusions: The predictive value of CFD for Fontan planning can be validated against an in vitro flow loop. The prediction accuracy can be affected by the mesh size, model shape complexity and flow competition.

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Hemodynamics of the Fontan Connection: An In-Vitro Study

Journal of Biomechanical Engineering ◽

10.1115/1.2794203 ◽

1995 ◽

Vol 117 (4) ◽

pp. 423-428 ◽

Cited By ~ 37

Author(s):

Young H. Kim ◽

P. G. Walker ◽

A. A. Fontaine ◽

S. Panchal ◽

A. E. Ensley ◽

...

Keyword(s):

Pressure Loss ◽

Superior Vena ◽

Fontan Operation ◽

Vena Cava ◽

In Vitro Study ◽

Magnetic Resonance Images ◽

Flow Loop ◽

Pressure Losses ◽

The Right

The Fontan operation is one in which the right heart is bypassed leaving the left ventricle to drive the blood through both the capillaries and the lungs, making it important to design an operation which is hemodynamically efficient. The object here was to relate the pressure in Fontan connections to its geometry with the aim of increasing the hemodynamically efficiency. From CT or magnetic resonance images, glass models were made of realistic atrio-pulmonary (AP) and cavo-pulmonary (CP) connections in which the right atrium and/or ventricle are bypassed. The glass models were connected to a steady flow loop and flow visualization, pressure and 3 component LDA measurements made. In the AP model the large atrium and curvature of the conduit created swirling patterns, the magnitude of which was similar to the axial velocity. This led to an inefficient flow and a subsequent large pressure loss (780 Pa). In contrast, the CP connection with a small intra-atrial chamber had reduced swirling and a significantly smaller pressure loss (400 Pa at 8 l.min) and was therefore a more efficient connection. There were, however, still pressure losses and it was found that these occurred where there was a large bending of the flow, such as from the superior vena cava to the MPA and from the MPA to the right pulmonary artery.

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In vitro testing of explanted shunt valves in hydrocephalic patients with suspected valve malfunction

Neurosurgical Review ◽

10.1007/s10143-021-01564-8 ◽

2021 ◽

Author(s):

Christoph Bettag ◽

Christian von der Brelie ◽

Florian Baptist Freimann ◽

Ulrich-Wilhelm Thomale ◽

Veit Rohde ◽

...

Keyword(s):

Flow Rate ◽

Clinical Symptoms ◽

Obstructive Hydrocephalus ◽

Flow Characteristics ◽

Normal Pressure ◽

Diagnostic Tools ◽

Programmable Valve ◽

Significant Difference ◽

Valve Malfunction

AbstractDiagnosis of symptomatic valve malfunction in hydrocephalic patients treated with VP-Shunt (VPS) might be difficult. Clinical symptoms such as headache or nausea are nonspecific, hence cerebrospinal fluid (CSF) over- or underdrainage can only be suspected but not proven. Knowledge concerning valve malfunction is still limited. We aim to provide data on the flow characteristics of explanted shunt valves in patients with suspected valve malfunction. An in vitro shunt laboratory setup was used to analyze the explanted valves under conditions similar to those in an implanted VPS. The differential pressure (DP) of the valve was adjusted stepwise to 20, 10, 6, and 4 cmH2O. The flow rate of the explanted and the regular flow rate of an identical reference valve were evaluated at the respective DPs. Twelve valves of different types (Codman CertasPlus valve n = 3, Miethke Shuntassistant valve n = 4, Codman Hakim programmable valve n = 3, DP component of Miethke proGAV 2.0 valve n = 2) from eight hydrocephalic patients (four male), in whom valve malfunction was assumed between 2016 and 2017, were replaced with a new valve. Four patients suffered from idiopathic normal pressure (iNPH), three patients from malresorptive and one patient from obstructive hydrocephalus. Post-hoc analysis revealed a significant difference (p < 0.001) of the flow rate between each explanted valve and their corresponding reference valve, at each DP. In all patients, significant alterations of flow rates were demonstrated, verifying a valve malfunction, which could not be objectified by the diagnostic tools used in the clinical routine. In cases with obscure clinical VPS insufficiency, valve deficiency should be considered.

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Surge in a Low-Speed Radial Compressor

Volume 1: Turbomachinery ◽

10.1115/98-gt-426 ◽

1998 ◽

Cited By ~ 3

Author(s):

Corine Meuleman ◽

Frank Willems ◽

Rick de Lange ◽

Bram de Jager

Keyword(s):

Flow Rate ◽

Pressure Rise ◽

Flow Coefficient ◽

Lumped Parameter Model ◽

Pressure Oscillations ◽

Vaned Diffuser ◽

Flow Angle ◽

Radial Compressor ◽

Low Speed ◽

Lumped Parameter

Surge is measured in a low-speed radial compressor with a vaned diffuser. For this system, the flow coefficient at surge is determined. This coefficient is a measure for the inducer inlet flow angle and is found to increase with increasing rotational speed. Moreover, the frequency and amplitude of the pressure oscillations during fully-developed surge are compared with results obtained with the Greitzer lumped parameter model. The measured surge frequency increases when the compressor mass flow is throttled to a smaller flow rate. Simulations show that the Greitzer model describes this relation reasonably well except for low rotational speeds. The predicted amplitude of the pressure rise oscillations is approximately two times too small when deep surge is met in the simulations. For classic surge, the agreement is worse. The amplitude is found to depend strongly on the shape of the compressor and throttle characteristic, which are not accurately known.

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Pharmacokinetics and dialytic clearance of apixaban during in vitro continuous renal replacement therapy

BMC Nephrology ◽

10.1186/s12882-021-02248-7 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Lauren Andrews ◽

Scott Benken ◽

Xing Tan ◽

Eric Wenzler

Keyword(s):

Renal Replacement Therapy ◽

Linear Regression ◽

Protein Binding ◽

Continuous Renal Replacement Therapy ◽

Replacement Therapy ◽

Flow Rate ◽

Systemic Exposure ◽

Flow Rates ◽

Filter Type

Abstract Background To evaluate the transmembrane clearance (CLTM) of apixaban during modeled in vitro continuous renal replacement therapy (CRRT), assess protein binding and circuit adsorption, and provide initial dosing recommendations. Methods Apixaban was added to the CRRT circuit and serial pre-filter bovine blood samples were collected along with post-filter blood and effluent samples. All experiments were performed in duplicate using continuous veno-venous hemofiltration (CVVH) and hemodialysis (CVVHD) modes, with varying filter types, flow rates, and point of CVVH replacement fluid dilution. Concentrations of apixaban and urea were quantified via liquid chromatography-tandem mass spectrometry. Plasma pharmacokinetic parameters for apixaban were estimated via noncompartmental analysis. CLTM was calculated via the estimated area under the curve (AUC) and by the product of the sieving/saturation coefficient (SC/SA) and flow rate. Two and three-way analysis of variance (ANOVA) models were built to assess the effects of mode, filter type, flow rate, and point of dilution on CLTM by each method. Optimal doses were suggested by matching the AUC observed in vitro to the systemic exposure demonstrated in Phase 2/3 studies of apixaban. Linear regression was utilized to provide dosing estimations for flow rates from 0.5–5 L/h. Results Mean adsorption to the HF1400 and M150 filters differed significantly at 38 and 13%, respectively, while mean (± standard deviation, SD) percent protein binding was 70.81 ± 0.01%. Effect of CVVH point of dilution did not differ across filter types, although CLTM was consistently significantly higher during CRRT with the HF1400 filter compared to the M150. The three-way ANOVA demonstrated improved fit when CLTM values calculated by AUC were used (adjusted R2 0.87 vs. 0.52), and therefore, these values were used to generate optimal dosing recommendations. Linear regression revealed significant effects of filter type and flow rate on CLTM by AUC, suggesting doses of 2.5–7.5 mg twice daily (BID) may be needed for flow rates ranging from 0.5–5 L/h, respectively. Conclusion For CRRT flow rates most commonly employed in clinical practice, the standard labeled 5 mg BID dose of apixaban is predicted to achieve target systemic exposure thresholds. The safety and efficacy of these proposed dosing regimens warrants further investigation in clinical studies.

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Flow variability and its physical causes in infusion technology: a systematic review of in vitro measurement and modeling studies

Biomedical Engineering / Biomedizinische Technik ◽

10.1515/bmt-2014-0148 ◽

2015 ◽

Vol 60 (4) ◽

Cited By ~ 6

Author(s):

Roland A. Snijder ◽

Maurits K. Konings ◽

Peter Lucas ◽

Toine C. Egberts ◽

Annemoon D. Timmerman

Keyword(s):

Systematic Review ◽

Adverse Effects ◽

Flow Rate ◽

Medical Errors ◽

Biomedical Literature ◽

Infusion Therapy ◽

Flow Variability ◽

Modeling Studies

AbstractInfusion therapy is medically and technically challenging and frequently associated with medical errors. When administering pharmaceuticals by means of infusion, dosing errors can occur due to flow rate variability. These dosing errors may lead to adverse effects. We aimed to systematically review the available biomedical literature for

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Scaling Formulae for the Wellbore Hydraulics Similitude with Drill Pipe Rotation and Eccentricity

10.2118/204637-ms ◽

2021 ◽

Author(s):

Thad Nosar ◽

Pooya Khodaparast ◽

Wei Zhang ◽

Amin Mehrabian

Keyword(s):

Power Law ◽

Flow Rate ◽

Annular Flow ◽

Rotation Speed ◽

Drilling Fluid ◽

Drill Pipe ◽

Flow Loop ◽

Annular Flows ◽

Fluid Rheology ◽

Pipe Rotation

Abstract Equivalent circulation density of the fluid circulation system in drilling rigs is determined by the frictional pressure losses in the wellbore annulus. Flow loop experiments are commonly used to simulate the annular wellbore hydraulics in the laboratory. However, proper scaling of the experiment design parameters including the drill pipe rotation and eccentricity has been a weak link in the literature. Our study uses the similarity laws and dimensional analysis to obtain a complete set of scaling formulae that would relate the pressure loss gradients of annular flows at the laboratory and wellbore scales while considering the effects of inner pipe rotation and eccentricity. Dimensional analysis is conducted for commonly encountered types of drilling fluid rheology, namely, Newtonian, power-law, and yield power-law. Appropriate dimensionless groups of the involved variables are developed to characterize fluid flow in an eccentric annulus with a rotating inner pipe. Characteristic shear strain rate at the pipe walls is obtained from the characteristic velocity and length scale of the considered annular flow. The relation between lab-scale and wellbore scale variables are obtained by imposing the geometric, kinematic, and dynamic similarities between the laboratory flow loop and wellbore annular flows. The outcomes of the considered scaling scheme is expressed in terms of closed-form formulae that would determine the flow rate and inner pipe rotation speed of the laboratory experiments in terms of the wellbore flow rate and drill pipe rotation speed, as well as other parameters of the problem, in such a way that the resulting Fanning friction factors of the laboratory and wellbore-scale annular flows become identical. Findings suggest that the appropriate value for lab flow rate and pipe rotation speed are linearly related to those of the field condition for all fluid types. The length ratio, density ratio, consistency index ratio, and power index determine the proportionality constant. Attaining complete similarity between the similitude and wellbore-scale annular flow may require the fluid rheology of the lab experiments to be different from the drilling fluid. The expressions of lab flow rate and rotational speed for the yield power-law fluid are identical to those of the power-law fluid case, provided that the yield stress of the lab fluid is constrained to a proper value.

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Self-Powered Multifunctional Instrumented Knee Implant

Volume 2: Mechanics and Behavior of Active Materials; Structural Health Monitoring; Bioinspired Smart Materials and Systems; Energy Harvesting; Emerging Technologies ◽

10.1115/smasis2018-8078 ◽

2018 ◽

Author(s):

Mohsen Safaei ◽

Steven R. Anton

Keyword(s):

Finite Element ◽

Energy Harvesting ◽

Knee Replacement ◽

Center Of Pressure ◽

Experimental Testing ◽

Sensory System ◽

Implant Design ◽

Total Force ◽

Self Powered

Computational modeling, instrumented linkages, optical technologies, MRI, and radiographic techniques have been widely used to study knee motion after total knee replacement (TKR) surgery. Information provided by these methods has helped designers to develop implants with better clinical performance and surgeons to obtain an improved understanding of the stability and mobility of the joint. Correspondingly, overall patient satisfaction with respect to the reduction in pain and recovery of normal functioning of the joint has been improving. However, about 20% of patients are still not fully satisfied with their surgical outcomes. The main obstacle in the current state-of-the-art is that a comprehensive post-operative understanding of knee balance is still unavailable, mostly due to a lack of in vivo data collected from the joint after surgery. This work presents an attempt to develop a self-powered instrumented knee implant for in vivo data acquisition. The knee sensory system in this study utilizes several embedded piezoelectric transducers in the tibial bearing of the knee replacement in order to provide sensing and energy harvesting capabilities. Through a series of analytical modeling, finite element simulation, and experimental testing, the performance of the suggested system is evaluated and a dimensionally optimized design of an instrumented TKR is achieved. More specifically, a comprehensive platform is established in order to combine the knowledge of embedded piezoelectric sensors and energy harvesters, musculoskeletal modeling of the knee joint, multiphysics finite element modeling, additive manufacturing techniques, image processing, and experimental knee loading simulation in order to achieve the experimentally validated and optimized instrumented knee implant design. The cumulative work presented in this article encompasses three main studies performed on the sensing performance of the proposed design: first, preliminary parametric studies of the effect of local dimensional and material parameters on the electromechanical behavior of the embedded sensory system; second, investigation of the ability to sense total force and center of pressure location; and third, evaluation of an enhanced system with the ability to sense compartmental forces and contact locations. Additionally, the energy harvesting capacity of the system is investigated to ensure the achievement of a fully self-powered sensory system. Results obtained from the experimental analysis of the system demonstrate the successful sensing and energy harvesting performance of the designs achieved in this study.

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