The Experts below are selected from a list of 312 Experts worldwide ranked by ideXlab platform
Keith E Cook - One of the best experts on this subject based on the ideXlab platform.
-
72-Hour in vivo evaluation of nitric oxide generating Artificial Lung gas exchange fibers in sheep.
Acta biomaterialia, 2019Co-Authors: Angela Lai, Caitlin T. Demarest, Chi Chi Do-nguyen, Rei Ukita, David J. Skoog, Neil M. Carleton, Kagya A. Amoako, Patrick J. Montoya, Keith E CookAbstract:Abstract The large, densely packed Artificial surface area of Artificial Lungs results in rapid clotting and device failure. Surface generated nitric oxide (NO) can be used to reduce platelet activation and coagulation on gas exchange fibers, while not inducing patient bleeding due to its short half-life in blood. To generate NO, Artificial Lungs can be manufactured with PDMS hollow fibers embedded with copper nanoparticles (Cu NP) and supplied with an infusion of the NO donor S-nitroso-N-acetyl-penicillamine (SNAP). The SNAP reacts with Cu NP to generate NO. This study investigates clot formation and gas exchange performance of Artificial Lungs with either NO-generating Cu-PDMS or standard polymethylpentene (PMP) fibers. One miniature Artificial Lung (MAL) made with 10 wt% Cu-PDMS hollow fibers and one PMP control MAL were attached to sheep in parallel in a veno-venous extracorporeal membrane oxygenation circuit (n = 8). Blood flow through each device was set at 300 mL/min, and each device received a SNAP infusion of 0.12 μmol/min. The ACT was between 110 and 180 s in all cases. Blood flow resistance was calculated as a measure of clot formation on the fiber bundle. Gas exchange experiments comparing the two groups were conducted every 24 h at blood flow rates of 300 and 600 mL/min. Devices were removed once the resistance reached 3x baseline (failure) or following 72 h. All devices were imaged using scanning electron microscopy (SEM) at the inlet, outlet, and middle of the fiber bundle. The Cu-PDMS NO generating MALs had a significantly smaller increase in resistance compared to the control devices. Resistance rose from 26 ± 8 and 23 ± 5 in the control and Cu-PDMS devices, respectively, to 35 ± 8 mmHg/(mL/min) and 72 ± 23 mmHg/(mL/min) at the end of each experiment. The resistance and SEM imaging of fiber surfaces demonstrate lower clot formation on Cu-PDMS fibers. Although not statistically significant, oxygen transfer for the Cu-PDMS MALs was 13.3% less than the control at 600 mL/min blood flow rate. Future in vivo studies with larger Cu–PDMS devices are needed to define gas exchange capabilities and anticoagulant activity over a long-term study at clinically relevant ACTs. Statement of Significance In Artificial Lungs, the large, densely-packed blood contacting surface area of the hollow fiber bundle is critical for gas exchange but also creates rapid, surface-generated clot requiring significant anticoagulation. Monitoring of anticoagulation, thrombosis, and resultant complications has kept permanent respiratory support from becoming a clinical reality. In this study, we use a hollow fiber material that generates nitric oxide (NO) to prevent platelet activation at the blood contacting surface. This material is tested in vivo in a miniature Artificial Lung and compared against the clinical standard. Results indicated significantly reduced clot formation. Surface-focused anticoagulation like this should reduce complication rates and allow for permanent respiratory support by extending the functional lifespan of Artificial Lungs and can further be applied to other medical devices.
-
Zwitterionic Poly-Carboxybetaine Coating Reduces Artificial Lung Thrombosis in Sheep and Rabbits
Social Science Research Network, 2019Co-Authors: Rei Ukita, Angela Lai, Caitlin T. Demarest, Chi Chi Do-nguyen, Neil M. Carleton, Xiaojie Lin, Noritsugu Naito, Shaoyi Jiang, Keith E CookAbstract:Abstract Current Artificial Lungs fail in 1–4 weeks due to surface-induced thrombosis. Biomaterial coatings may be applied to anticoagulate Artificial surfaces, but none have shown marked long-term effectiveness. Poly-carboxybetaine (pCB) coatings have shown promising results in reducing protein and platelet-fouling in vitro. However, in vivo hemocompatibility remains to be investigated. Thus, three different pCB-grafting approaches to Artificial Lung surfaces were first investigated: 1) graft-to approach using 3,4-dihydroxyphenylalanine (DOPA) conjugated with pCB (DOPA-pCB); 2) graft-from approach using the Activators ReGenerated by Electron Transfer method of atom transfer radical polymerization (ARGET-ATRP); and 3) graft-to approach using pCB randomly copolymerized with hydrophobic moieties. One device coated with each of these methods and one uncoated device were attached in parallel within a veno-venous sheep extracorporeal circuit with no continuous anticoagulation (N = 5 circuits). The DOPA-pCB approach showed the least increase in blood flow resistance and the lowest incidence of device failure over 36-hours. Next, we further investigated the impact of tip-to-tip DOPA-pCB coating in a 4-hour rabbit study with veno-venous micro-Artificial Lung circuit at a higher activated clotting time of 220–300 s (N ≥ 5). Here, DOPA-pCB reduced fibrin formation (p = 0.06) and gross thrombus formation by 59% (p Statement of Significance Chronic Lung diseases lead to 168,000 deaths each year in America, but only 2300 Lung transplantations happen each year. Hollow fiber membrane oxygenators are clinically used as Artificial Lungs to provide respiratory support for patients, but their long-term viability is hindered by surface-induced clot formation that leads to premature device failure. Among different coatings investigated for blood-contacting applications, poly-carboxybetaine (pCB) coatings have shown remarkable reduction in protein adsorption in vitro. However, their efficacy in vivo remains unclear. This is the first work that investigates various pCB-coating methods on Artificial Lung surfaces and their biocompatibility in sheep and rabbit studies. This work highlights the promise of applying pCB coatings on Artificial Lungs to extend its durability and enable long-term respiratory support for Lung disease patients.
-
Fourteen Day In Vivo Testing of a Compliant Thoracic Artificial Lung.
ASAIO journal (American Society for Artificial Internal Organs : 1992), 2017Co-Authors: David J. Skoog, Christopher N. Scipione, Rebecca E. Schewe, Kelly L. Koch, Amit Iyengar, Joshua R. Pohlmann, David S. Demos, Ahmed B. Suhaib, Keith E CookAbstract:The compliant thoracic Artificial Lung (cTAL) has been studied in acute in vivo and in vitro experiments. The cTAL's long-term function and potential use as a bridge to Lung transplantation are assessed presently. The cTAL without anticoagulant coatings was attached to sheep (n = 5) via the pulmonary artery and left atrium for 14 days. Systemic heparin anticoagulation was used. Compliant thoracic Artificial Lung resistance, cTAL gas exchange, hematologic parameters, and organ function were recorded. Two sheep were euthanized for nondevice-related issues. The cTAL's resistance averaged 1.04 ± 0.05 mmHg/(L/min) with no statistically significant increases. The cTAL transferred 180 ± 8 ml/min of oxygen with 3.18 ± 0.05 L/min of blood flow. Except for transient surgical effects, organ function markers were largely unchanged. Necropsies revealed pulmonary edema and atelectasis but no other derangements. Hemoglobin levels dropped with device attachment but remained steady at 9.0 ± 0.1 g/dl thereafter. In a 14 day experiment, the cTAL without anticoagulant coatings exhibited minimal clot formation. Sheep physiology was largely unchanged except for device attachment-related hemodilution. This suggests that patients treated with the cTAL should not require multiple blood transfusions. Once tested with anticoagulant coatings and plasma resistant gas exchange fiber, the cTAL could serve as a bridge to transplantation.
-
Use of a Low Resistance Compliant Thoracic Artificial Lung in the Pulmonary Artery to Pulmonary Artery Configuration
The Journal of thoracic and cardiovascular surgery, 2013Co-Authors: Christopher N. Scipione, Rebecca E. Schewe, Kelly L. Koch, Andrew Shaffer, Amit Iyengar, Keith E CookAbstract:Background Thoracic Artificial Lungs have been proposed as a bridge to transplant in patients with end-stage Lung disease. Systemic embolic complications can occur after thoracic Artificial Lung attachment in the pulmonary artery to left atrium configuration. Therefore, we evaluated the function of a compliant thoracic Artificial Lung attached via the proximal pulmonary artery to distal main pulmonary artery configuration. Methods The compliant thoracic Artificial Lung was attached to 5 sheep (63 ± 0.9 kg) in the proximal pulmonary artery to distal main pulmonary artery configuration. Device function and animal hemodynamics were assessed at baseline and with approximately 60%, 75%, and 90% of cardiac output diverted to the compliant thoracic Artificial Lung. At each condition, dobutamine (0 and 5 μg·kg −1 ·min −1 ) was used to simulate rest and exercise conditions. Results At rest, cardiac output decreased from 6.20 ± 0.53 L/min at baseline to 5.40 ± 0.43, 4.66 ± 0.31, and 4.05 ± 0.27 L/min with 60%, 75%, and 90% of cardiac output to the compliant thoracic Artificial Lung, respectively ( P P = .82, P = .19, and P Conclusions Use of a compliant thoracic Artificial Lung may be feasible in the proximal pulmonary artery to distal main pulmonary artery setting if its blood flow is held at less than 75% of cardiac output. To ensure a decrease in cardiac output of less than 10%, a blood flow rate less than 60% of cardiac output is advised.
-
hemodynamic design requirements for in series thoracic Artificial Lung attachment in a model of pulmonary hypertension
Asaio Journal, 2012Co-Authors: Begum Akay, Kelly L. Koch, Daniele Camboni, Ayushi Kawatra, Julie A Foucher, Keith E CookAbstract:Recent thoracic Artificial Lung (TAL) prototypes have impedances lower than the natural Lung. With these devices, proximal pulmonary artery (PA) to distal PA TAL attachment may be possible in patients without right ventricular dysfunction. This study examined the relationship between pulmonary system impedance and cardiac output (CO) to create TAL design constraints. A circuit with adjustable resistance and compliance (C) was attached in a PA-PA fashion with the pulmonary circulation of seven sheep with chronic pulmonary hypertension. The pulmonary system zeroth harmonic impedance modulus (Z(0)) was increased by 1, 2.5, and 4 mmHg/(L/min) above baseline. At each Z(0), C was set to 0, 0.34, and 2.1 ml/mmHg. The change in pulmonary system zeroth and first harmonic impedance moduli (ΔZ(0) and ΔZ(1)), the percent change in CO (%ΔCO), and the inlet and outlet anastomoses resistances were calculated for each situation. Results indicate that ΔZ(0) (p < 0.001) but not ΔZ(1) (p = 0.5) had a significant effect on %ΔCO and that %ΔCO = -7.45*ΔZ(0) (R(2) = 0.57). Inlet and outlet anastomoses resistances averaged 0.77 ± 0.16 and 0.10 ± 0.19 mmHg/(L/min), respectively, and the relationship between %ΔCO and TAL resistance, R(T), in mmHg/(L/min) was determined to be %ΔCO = -(7.45f)×(R(T) + 0.87), in which f = the fraction of CO through the TAL. Thus, newer TAL designs can limit %ΔCO to less than 10% if f < 0.75.
Joseph A Potkay - One of the best experts on this subject based on the ideXlab platform.
-
Design Analysis and Optimization of a Single-Layer PDMS Microfluidic Artificial Lung
IEEE transactions on bio-medical engineering, 2018Co-Authors: Alex J. Thompson, Lindsay J., Thomas James Plegue, Joseph A PotkayAbstract:Objective: Microfluidic Artificial Lungs (μALs) are being researched for future clinical use due to the potential for increased gas exchange efficiency, small blood contacting surface area, small priming volume, and biomimetic blood flow paths. However, a current roadblock to clinical use is the need to stack hundreds to thousands of these small-scale μALs in parallel to reach clinically relevant blood flows. The need for so many layers not only increases the complexity and projected cost to manufacture a μAL, but also could result in devices which are cumbersome, and, therefore, not suitable for portable Artificial Lung systems. Methods: Here, we describe the design analysis and optimization of a single-layer μAL that simultaneously calculates rated blood flow, blood contacting surface area, blood volume, pressure drop, and shear stress as a function of blood channel height using previously developed closed-form mathematical equations. A μAL designed using this procedure is then implemented and tested. Results: The resulting device exhibits a rated flow of 17 mL/min and reduces the number of layers required for clinically relevant μAL devices by a factor of up to 32X compared to previous work. Conclusion: This procedure could significantly reduce manufacturing complexity as well as eliminate a barrier to the clinical application of these promising devices. Significance: The described method results in the highest rated flow for any single-layer μAL to date.
-
a small scale rolled membrane microfluidic Artificial Lung designed towards future large area manufacturing
Biomicrofluidics, 2017Co-Authors: Alex J. Thompson, Alvaro Rojaspena, L H Marks, Marcus J Goudie, Hitesh Handa, Joseph A PotkayAbstract:Artificial Lungs have been used in the clinic for multiple decades to supplement patient pulmonary function. Recently, small-scale microfluidic Artificial Lungs (μAL) have been demonstrated with large surface area to blood volume ratios, biomimetic blood flow paths, and pressure drops compatible with pumpless operation. Initial small-scale microfluidic devices with blood flow rates in the μl/min to ml/min range have exhibited excellent gas transfer efficiencies; however, current manufacturing techniques may not be suitable for scaling up to human applications. Here, we present a new manufacturing technology for a microfluidic Artificial Lung in which the structure is assembled via a continuous “rolling” and bonding procedure from a single, patterned layer of polydimethyl siloxane (PDMS). This method is demonstrated in a small-scale four-layer device, but is expected to easily scale to larger area devices. The presented devices have a biomimetic branching blood flow network, 10 μm tall Artificial capillari...
-
a small scale rolled membrane microfluidic Artificial Lung designed towards future large area manufacturing
Biomicrofluidics, 2017Co-Authors: Alex J. Thompson, Alvaro Rojaspena, L H Marks, Marcus J Goudie, Hitesh Handa, Joseph A PotkayAbstract:Artificial Lungs have been used in the clinic for multiple decades to supplement patient pulmonary function. Recently, small-scale microfluidic Artificial Lungs (μAL) have been demonstrated with large surface area to blood volume ratios, biomimetic blood flow paths, and pressure drops compatible with pumpless operation. Initial small-scale microfluidic devices with blood flow rates in the μl/min to ml/min range have exhibited excellent gas transfer efficiencies; however, current manufacturing techniques may not be suitable for scaling up to human applications. Here, we present a new manufacturing technology for a microfluidic Artificial Lung in which the structure is assembled via a continuous “rolling” and bonding procedure from a single, patterned layer of polydimethyl siloxane (PDMS). This method is demonstrated in a small-scale four-layer device, but is expected to easily scale to larger area devices. The presented devices have a biomimetic branching blood flow network, 10 μm tall Artificial capillaries, and a 66 μm thick gas transfer membrane. Gas transfer efficiency in blood was evaluated over a range of blood flow rates (0.1–1.25 ml/min) for two different sweep gases (pure O2, atmospheric air). The achieved gas transfer data closely follow predicted theoretical values for oxygenation and CO2 removal, while pressure drop is marginally higher than predicted. This work is the first step in developing a scalable method for creating large area microfluidic Artificial Lungs. Although designed for microfluidic Artificial Lungs, the presented technique is expected to result in the first manufacturing method capable of simply and easily creating large area microfluidic devices from PDMS.
-
In vitro evaluation and in vivo demonstration of a biomimetic, hemocompatible, microfluidic Artificial Lung
Lab on a chip, 2015Co-Authors: Kyle M. Kovach, Michael Labarbera, Michelle Moyer, B. L. Cmolik, E. Van Lunteren, A. Sen Gupta, Jeffrey R. Capadona, Joseph A PotkayAbstract:Despite the promising potential of microfluidic Artificial Lungs, current designs suffer from short functional lifetimes due to surface chemistry and blood flow patterns that act to reduce hemocompatibility. Here, we present the first microfluidic Artificial Lung featuring a hemocompatible surface coating and a biomimetic blood path. The polyethylene-glycol (PEG) coated microfluidic Lung exhibited a significantly improved in vitro lifetime compared to uncoated controls as well as consistent and significantly improved gas exchange over the entire testing period. Enabled by our hemocompatible PEG coating, we additionally describe the first extended (3 h) in vivo demonstration of a microfluidic Artificial Lung.
-
bio inspired efficient Artificial Lung employing air as the ventilating gas
Lab on a Chip, 2011Co-Authors: Joseph A Potkay, Michael J Magnetta, Abigail Vinson, Brian CmolikAbstract:Artificial Lungs have recently been utilized to rehabilitate patients suffering from Lung diseases. However, significant advances in gas exchange, biocompatibility, and portability are required to realize their full clinical potential. Here, we have focused on the issues of gas exchange and portability and report a small-scale, microfabricated Artificial Lung that uses new mathematical modeling and a bio-inspired design to achieve oxygen exchange efficiencies much larger than current devices, thereby enabling air to be utilized as the ventilating gas. This advancement eliminates the need for pure oxygen required by conventional Artificial Lung systems and is achieved through a device with feature sizes and structure similar to that in the natural Lung. This advancement represents a significant step towards creating the first truly portable and implantable Artificial Lung systems for the ambulatory care of patients suffering from Lung diseases.
Robert H Bartlett - One of the best experts on this subject based on the ideXlab platform.
-
pediatric Artificial Lung a low resistance pumpless Artificial Lung alleviates an acute lamb model of increased right ventricle afterload
Asaio Journal, 2017Co-Authors: Fares Alghanem, Robert H Bartlett, Uditha Piyumindri Fernando, Benjamin S Bryner, Emilia M Jahangir, John M Trahanas, Hayley R Hoffman, Alvaro Rojaspena, Ronald B HirschlAbstract:Lung disease in children often results in pulmonary hypertension and right heart failure. The availability of a pediatric Artificial Lung (PAL) would open new approaches to the management of these conditions by bridging to recovery in acute disease or transplantation in chronic disease. This study investigates the efficacy of a novel PAL in alleviating an animal model of pulmonary hypertension and increased right ventricle afterload. Five juvenile lambs (20-30 kg) underwent PAL implantation in a pulmonary artery to left atrium configuration. Induction of disease involved temporary, reversible occlusion of the right main pulmonary artery. Hemodynamics, pulmonary vascular input impedance, and right ventricle efficiency were measured under 1) baseline, 2) disease, and 3) disease + PAL conditions. The disease model altered hemodynamics variables in a manner consistent with pulmonary hypertension. Subsequent PAL attachment improved pulmonary artery pressure (p = 0.018), cardiac output (p = 0.050), pulmonary vascular input impedance (Z.0 p = 0.028; Z.1 p = 0.058), and right ventricle efficiency (p = 0.001). The PAL averaged resistance of 2.3 ± 0.8 mm Hg/L/min and blood flow of 1.3 ± 0.6 L/min. This novel low-resistance PAL can alleviate pulmonary hypertension in an acute animal model and demonstrates potential for use as a bridge to Lung recovery or transplantation in pediatric patients with significant pulmonary hypertension refractory to medical therapies.
-
the implantable pediatric Artificial Lung interim report on the development of an end stage Lung failure model
Asaio Journal, 2015Co-Authors: Fares Alghanem, Robert H Bartlett, Benjamin S Bryner, John M Trahanas, Hayley R Hoffman, Alvaro Rojaspena, Ryan P Davis, Marie S Cornell, Ronald B HirschlAbstract:An implantable pediatric Artificial Lung (PAL) may serve as a bridge to Lung transplantation for children with end-stage Lung failure (ESLF); however, an animal model of pediatric Lung failure is needed to evaluate the efficacy of PAL before it can enter clinical trials. The objective of this study was to assess ligation of the right pulmonary artery (rPA) as a model for pediatric ESLF. Seven lambs weighing 20-30 kg underwent rPA ligation and were recovered and monitored for up to 4 days. Intraoperatively, rPA ligation significantly increased physiologic dead space fraction (Vd/Vt; baseline = 48.6 ± 5.7%, rPA ligation = 60.1 ± 5.2%, p = 0.012), mean pulmonary arterial pressure (mPPA; baseline = 17.4 ± 2.2 mm Hg, rPA ligation = 28.5 ± 5.2 mm Hg, p < 0.001), and arterial partial pressure of carbon dioxide (baseline = 40.4 ± 9.3 mm Hg, rPA ligation = 57.3 ± 12.7 mm Hg, p = 0.026). Of the seven lambs, three were unable to be weaned from mechanical ventilation postoperatively, three were successfully weaned but suffered cardiorespiratory failure within 4 days, and one survived all 4 days. All four animals that were successfully weaned from mechanical ventilation had persistent pulmonary hypertension (mPPA = 28.6 ± 2.2 mm Hg) and remained tachypneic (respiratory rate = 63 ± 21 min). Three of the four recovered lambs required supplemental oxygen. We conclude that rPA ligation creates the physiologic derangements commonly seen in pediatric ESLF and may be suitable for testing and implanting a PAL.
-
an investigation of pulsatile flow past two cylinders as a model of blood flow in an Artificial Lung
International Journal of Heat and Mass Transfer, 2011Co-Authors: Khalil Khanafer, Ronald B Hirschl, Robert H Bartlett, Joseph L BullAbstract:Pulsatile flow across two circular cylinders with different geometric arrangements is studied experimentally using the particle image velocimetry method and numerically using the finite element method. This investigation is motivated the need to optimize gas transfer and fluid mechanical impedance for a total Artificial Lung, in which the right heart pumps blood across a bundle of hollow microfibers. Vortex formation was found to occur at lower Reynolds numbers in pulsatile flow than in steady flow, and the vortex structure depends strongly on the geometric arrangement of the cylinders and on the Reynolds and Stokes numbers.
-
In-parallel Artificial Lung attachment at high flows in normal and pulmonary hypertension models.
The Annals of thoracic surgery, 2010Co-Authors: Begum Akay, Robert H Bartlett, Joshua R. Pohlmann, Daniele Camboni, Junewai L. Reoma, John M. Albert, Ayushi Kawatra, Ayanna D. Gouch, Keith E CookAbstract:Background End-stage Lung disease patients who require a thoracic Artificial Lung (TAL) must be extubated and rehabilitated prior to Lung transplantation. The purpose of this study is to evaluate hemodynamics and TAL function under simulated rest and exercise conditions in normal and pulmonary hypertension sheep models. Methods The TAL, the MC3 BioLung (MC3, Inc, Ann Arbor, MI), was attached between the pulmonary artery and left atrium in nine normal sheep and eight sheep with chronic pulmonary hypertension. An adjustable band was placed around the distal pulmonary artery to control the percentage of cardiac output (CO) diverted to the TAL. Pulmonary system hemodynamics and TAL function were assessed at baseline (no flow to the TAL) and with approximately 60%, 75%, and 90% of CO diverted to the TAL. Intravenous dobutamine (0, 2, and 5 mcg · kg −1 · min −1 ) was used to simulate rest and exercise conditions. Results At 0 and 2 mcg · kg −1 · min −1 , CO did not change significantly with flow diversion to the TAL for both models. At 5 mcg · kg −1 · min −1 , CO decreased with increasing TAL flow up to 28% ± 5% in normal sheep and 23% ± 5% in pulmonary hypertension sheep at 90% flow diversion to the Artificial Lung. In normal sheep, the pulmonary system zeroth harmonic impedance modulus, Z 0 , increased with increasing flow diversion. In hypertensive sheep, Z 0 decreased at 60% and 75% flow diversion and returned to baseline levels at 90%. The TAL outlet blood oxygen saturation was 95% or greater under all conditions. Conclusions Pulmonary artery to left atrial TAL use will not decrease CO during rest or mild exercise but may not allow more vigorous exercise.
-
Oxygen and carbon dioxide transport in time-dependent blood flow past fiber rectangular arrays
Physics of Fluids, 2009Co-Authors: Jennifer R. Zierenberg, Ronald B Hirschl, Robert H Bartlett, Hideki Fujioka, James B. GrotbergAbstract:The influence of time-dependent flows on oxygen and carbon dioxide transport for blood flow past fiber arrays arranged in in-line and staggered configurations was computationally investigated as a model for an Artificial Lung. Both a pulsatile flow, which mimics the flow leaving the right heart and passing through a compliance chamber before entering the Artificial Lung, and a right ventricular flow, which mimics flow leaving the right heart and directly entering the Artificial Lung, were considered in addition to a steady flow. The pulsatile flow was modeled as a sinusoidal perturbation superimposed on a steady flow while the right ventricular flow was modeled to accurately depict the period of flow acceleration (increasing flow) and deceleration (decreasing flow) during systole followed by zero flow during diastole. It was observed that the pulsatile flow yielded similar gas transport as compared to the steady flow, while the right ventricular flow resulted in smaller gas transport, with the decrease in...
Ronald B Hirschl - One of the best experts on this subject based on the ideXlab platform.
-
pediatric Artificial Lung a low resistance pumpless Artificial Lung alleviates an acute lamb model of increased right ventricle afterload
Asaio Journal, 2017Co-Authors: Fares Alghanem, Robert H Bartlett, Uditha Piyumindri Fernando, Benjamin S Bryner, Emilia M Jahangir, John M Trahanas, Hayley R Hoffman, Alvaro Rojaspena, Ronald B HirschlAbstract:Lung disease in children often results in pulmonary hypertension and right heart failure. The availability of a pediatric Artificial Lung (PAL) would open new approaches to the management of these conditions by bridging to recovery in acute disease or transplantation in chronic disease. This study investigates the efficacy of a novel PAL in alleviating an animal model of pulmonary hypertension and increased right ventricle afterload. Five juvenile lambs (20-30 kg) underwent PAL implantation in a pulmonary artery to left atrium configuration. Induction of disease involved temporary, reversible occlusion of the right main pulmonary artery. Hemodynamics, pulmonary vascular input impedance, and right ventricle efficiency were measured under 1) baseline, 2) disease, and 3) disease + PAL conditions. The disease model altered hemodynamics variables in a manner consistent with pulmonary hypertension. Subsequent PAL attachment improved pulmonary artery pressure (p = 0.018), cardiac output (p = 0.050), pulmonary vascular input impedance (Z.0 p = 0.028; Z.1 p = 0.058), and right ventricle efficiency (p = 0.001). The PAL averaged resistance of 2.3 ± 0.8 mm Hg/L/min and blood flow of 1.3 ± 0.6 L/min. This novel low-resistance PAL can alleviate pulmonary hypertension in an acute animal model and demonstrates potential for use as a bridge to Lung recovery or transplantation in pediatric patients with significant pulmonary hypertension refractory to medical therapies.
-
the implantable pediatric Artificial Lung interim report on the development of an end stage Lung failure model
Asaio Journal, 2015Co-Authors: Fares Alghanem, Robert H Bartlett, Benjamin S Bryner, John M Trahanas, Hayley R Hoffman, Alvaro Rojaspena, Ryan P Davis, Marie S Cornell, Ronald B HirschlAbstract:An implantable pediatric Artificial Lung (PAL) may serve as a bridge to Lung transplantation for children with end-stage Lung failure (ESLF); however, an animal model of pediatric Lung failure is needed to evaluate the efficacy of PAL before it can enter clinical trials. The objective of this study was to assess ligation of the right pulmonary artery (rPA) as a model for pediatric ESLF. Seven lambs weighing 20-30 kg underwent rPA ligation and were recovered and monitored for up to 4 days. Intraoperatively, rPA ligation significantly increased physiologic dead space fraction (Vd/Vt; baseline = 48.6 ± 5.7%, rPA ligation = 60.1 ± 5.2%, p = 0.012), mean pulmonary arterial pressure (mPPA; baseline = 17.4 ± 2.2 mm Hg, rPA ligation = 28.5 ± 5.2 mm Hg, p < 0.001), and arterial partial pressure of carbon dioxide (baseline = 40.4 ± 9.3 mm Hg, rPA ligation = 57.3 ± 12.7 mm Hg, p = 0.026). Of the seven lambs, three were unable to be weaned from mechanical ventilation postoperatively, three were successfully weaned but suffered cardiorespiratory failure within 4 days, and one survived all 4 days. All four animals that were successfully weaned from mechanical ventilation had persistent pulmonary hypertension (mPPA = 28.6 ± 2.2 mm Hg) and remained tachypneic (respiratory rate = 63 ± 21 min). Three of the four recovered lambs required supplemental oxygen. We conclude that rPA ligation creates the physiologic derangements commonly seen in pediatric ESLF and may be suitable for testing and implanting a PAL.
-
an investigation of pulsatile flow past two cylinders as a model of blood flow in an Artificial Lung
International Journal of Heat and Mass Transfer, 2011Co-Authors: Khalil Khanafer, Ronald B Hirschl, Robert H Bartlett, Joseph L BullAbstract:Pulsatile flow across two circular cylinders with different geometric arrangements is studied experimentally using the particle image velocimetry method and numerically using the finite element method. This investigation is motivated the need to optimize gas transfer and fluid mechanical impedance for a total Artificial Lung, in which the right heart pumps blood across a bundle of hollow microfibers. Vortex formation was found to occur at lower Reynolds numbers in pulsatile flow than in steady flow, and the vortex structure depends strongly on the geometric arrangement of the cylinders and on the Reynolds and Stokes numbers.
-
Oxygen and carbon dioxide transport in time-dependent blood flow past fiber rectangular arrays
Physics of Fluids, 2009Co-Authors: Jennifer R. Zierenberg, Ronald B Hirschl, Robert H Bartlett, Hideki Fujioka, James B. GrotbergAbstract:The influence of time-dependent flows on oxygen and carbon dioxide transport for blood flow past fiber arrays arranged in in-line and staggered configurations was computationally investigated as a model for an Artificial Lung. Both a pulsatile flow, which mimics the flow leaving the right heart and passing through a compliance chamber before entering the Artificial Lung, and a right ventricular flow, which mimics flow leaving the right heart and directly entering the Artificial Lung, were considered in addition to a steady flow. The pulsatile flow was modeled as a sinusoidal perturbation superimposed on a steady flow while the right ventricular flow was modeled to accurately depict the period of flow acceleration (increasing flow) and deceleration (decreasing flow) during systole followed by zero flow during diastole. It was observed that the pulsatile flow yielded similar gas transport as compared to the steady flow, while the right ventricular flow resulted in smaller gas transport, with the decrease in...
-
pulsatile flow past multiple cylinders a model study of blood flow in an Artificial Lung
International Conference on Biomedical Engineering, 2008Co-Authors: Yuchun Lin, Khalil Khanafer, Ronald B Hirschl, Robert H Bartlett, Joseph L BullAbstract:Pulsatile flow across two circular cylinders with different geometric arrangements is studied experimentally using particle image velocimetry method and numerically using the finite element method. This investigation is motivated by optimizing the design of a total Artificial Lung (TAL), a potential bridge to Lung transplantation. Blood flow through the TAL is generated entirely by the right ventricle of the heart and no external pump is utilized, thus blood flow inside the TAL is pulsatile. The oxygen-poor blood flows across a bundle of hollow fibers that oxygen-rich air flows through. Understanding time-dependent flow around these fibers is crucial for optimizing design since convection is the dominant transport mechanism in the bulk blood flow. The vortex structures resulting from three different arrangements of cylinders (tandem, side-by-side, staggered) in pulsatile flow with Reynolds numbers of 1, 3, and 5 and Stokes numbers of 0.18 and 0.37 were investigated. Consistent results were observed in the numerical and experimental results. These results reveal that the vortex structure depends strongly on the geometric arrangement of the cylinders. The vortex strength is highly dependent on the Reynolds and Stokes numbers. These findings suggest design criteria for enhancing mixing and reducing pressure drop across the TAL.
Alex J. Thompson - One of the best experts on this subject based on the ideXlab platform.
-
Low-Resistance, Concentric-Gated Pediatric Artificial Lung for End-Stage Lung Failure.
ASAIO journal (American Society for Artificial Internal Organs : 1992), 2020Co-Authors: Alex J. Thompson, Skylar Buchan, Benjamin D. Carr, Clinton Poling, Mckenzie Hayes, Uditha Piyumindri Fernando, Andreas Kaesler, Peter C. Schlanstein, Felix Hesselmann, Jutta ArensAbstract:Children with end-stage Lung failure awaiting Lung transplant would benefit from improvements in Artificial Lung technology allowing for wearable pulmonary support as a bridge-to-transplant therapy. In this work, we designed, fabricated, and tested the Pediatric MLung-a dual-inlet hollow fiber Artificial Lung based on concentric gating, which has a rated flow of 1 L/min, and a pressure drop of 25 mm Hg at rated flow. This device and future iterations of the current design are designed to relieve pulmonary arterial hypertension, provide pulmonary support, reduce ventilator-associated injury, and allow for more effective therapy of patients with end-stage Lung disease, including bridge-to-transplant treatment.
-
Design Analysis and Optimization of a Single-Layer PDMS Microfluidic Artificial Lung
IEEE transactions on bio-medical engineering, 2018Co-Authors: Alex J. Thompson, Lindsay J., Thomas James Plegue, Joseph A PotkayAbstract:Objective: Microfluidic Artificial Lungs (μALs) are being researched for future clinical use due to the potential for increased gas exchange efficiency, small blood contacting surface area, small priming volume, and biomimetic blood flow paths. However, a current roadblock to clinical use is the need to stack hundreds to thousands of these small-scale μALs in parallel to reach clinically relevant blood flows. The need for so many layers not only increases the complexity and projected cost to manufacture a μAL, but also could result in devices which are cumbersome, and, therefore, not suitable for portable Artificial Lung systems. Methods: Here, we describe the design analysis and optimization of a single-layer μAL that simultaneously calculates rated blood flow, blood contacting surface area, blood volume, pressure drop, and shear stress as a function of blood channel height using previously developed closed-form mathematical equations. A μAL designed using this procedure is then implemented and tested. Results: The resulting device exhibits a rated flow of 17 mL/min and reduces the number of layers required for clinically relevant μAL devices by a factor of up to 32X compared to previous work. Conclusion: This procedure could significantly reduce manufacturing complexity as well as eliminate a barrier to the clinical application of these promising devices. Significance: The described method results in the highest rated flow for any single-layer μAL to date.
-
a small scale rolled membrane microfluidic Artificial Lung designed towards future large area manufacturing
Biomicrofluidics, 2017Co-Authors: Alex J. Thompson, Alvaro Rojaspena, L H Marks, Marcus J Goudie, Hitesh Handa, Joseph A PotkayAbstract:Artificial Lungs have been used in the clinic for multiple decades to supplement patient pulmonary function. Recently, small-scale microfluidic Artificial Lungs (μAL) have been demonstrated with large surface area to blood volume ratios, biomimetic blood flow paths, and pressure drops compatible with pumpless operation. Initial small-scale microfluidic devices with blood flow rates in the μl/min to ml/min range have exhibited excellent gas transfer efficiencies; however, current manufacturing techniques may not be suitable for scaling up to human applications. Here, we present a new manufacturing technology for a microfluidic Artificial Lung in which the structure is assembled via a continuous “rolling” and bonding procedure from a single, patterned layer of polydimethyl siloxane (PDMS). This method is demonstrated in a small-scale four-layer device, but is expected to easily scale to larger area devices. The presented devices have a biomimetic branching blood flow network, 10 μm tall Artificial capillari...
-
a small scale rolled membrane microfluidic Artificial Lung designed towards future large area manufacturing
Biomicrofluidics, 2017Co-Authors: Alex J. Thompson, Alvaro Rojaspena, L H Marks, Marcus J Goudie, Hitesh Handa, Joseph A PotkayAbstract:Artificial Lungs have been used in the clinic for multiple decades to supplement patient pulmonary function. Recently, small-scale microfluidic Artificial Lungs (μAL) have been demonstrated with large surface area to blood volume ratios, biomimetic blood flow paths, and pressure drops compatible with pumpless operation. Initial small-scale microfluidic devices with blood flow rates in the μl/min to ml/min range have exhibited excellent gas transfer efficiencies; however, current manufacturing techniques may not be suitable for scaling up to human applications. Here, we present a new manufacturing technology for a microfluidic Artificial Lung in which the structure is assembled via a continuous “rolling” and bonding procedure from a single, patterned layer of polydimethyl siloxane (PDMS). This method is demonstrated in a small-scale four-layer device, but is expected to easily scale to larger area devices. The presented devices have a biomimetic branching blood flow network, 10 μm tall Artificial capillaries, and a 66 μm thick gas transfer membrane. Gas transfer efficiency in blood was evaluated over a range of blood flow rates (0.1–1.25 ml/min) for two different sweep gases (pure O2, atmospheric air). The achieved gas transfer data closely follow predicted theoretical values for oxygenation and CO2 removal, while pressure drop is marginally higher than predicted. This work is the first step in developing a scalable method for creating large area microfluidic Artificial Lungs. Although designed for microfluidic Artificial Lungs, the presented technique is expected to result in the first manufacturing method capable of simply and easily creating large area microfluidic devices from PDMS.
