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Electronic cigarettes (e-cigs) fundamentally differ from tobacco cigarettes in their generation of liquid-based aerosols. Investigating how e-cig aerosols behave when inhaled into the dynamic environment of the lung is important for understanding vaping-related exposure and toxicity. A ventilated artificial lung model was developed to replicate the ventilatory and environmental features of the human lung and study their impact on the characteristics of inhaled e-cig aerosols from simulated vaping scenarios. Compared to static conditions, normal breathing decreased peak particle number concentrations (PNCs) and area under the curve (AUC) by 40% and 70%, respectively, and increased particle decay rates fourfold. However, even with ventilation, intrapulmonary PNC levels exceeded 2 × 106 particles/mL in a 4-puff vaping session. Both respiratory rate and tidal volume modulated e-cig aerosol exposure in a manner inversely proportional to minute ventilation. The modeled lung environment (37 °C, 88% relative humidity) also significantly altered particle size distributions by facilitating aerosol transformations such as hygroscopic growth, which further impacted e-cig aerosol exposure and particle removal. This work highlights the dynamic nature of intrapulmonary exposures and underscores the need to account for lung physiology and environmental factors when assessing inhaled e-cig aerosols. [ABSTRACT FROM AUTHOR]

Introduction: The performance of an oxygenator, as found in literature, is evaluated according to protocols that define standard values of the gas content in the inlet blood. However, when dealing with simulations of lung insufficiency, a more extensive evaluation is needed. This work aims to investigate and assess the gas exchange performance of an oxygenator for different input values of gas content in blood. Methods: Three commercially available oxygenators with different membrane surfaces were investigated in a mock loop for three blood flow rates (0.5l/min, 1l/min, and 5l/min) and two gas-to-blood ratios (1:1, and 15:1). The initial CO2 and O2 partial pressures (pCO2 and pO2) in blood were set to ≥ 100 mmHg and ≤10 mmHg, respectively. For each ratio, the efficiency, defined as the ratio between the difference of pressure inlet and outlet and the inlet pCO2 (pCO2(i)), was calculated. Results: The CO2 elimination in an oxygenator was higher for higher pCO2(i). While for a pCO2(i) of 100 mmHg, an oxygenator eliminated 80 mmHg, the same oxygenator at the same conditions eliminated 5 mmHg CO2 when pCO2(i) was 10 mmHg. The efficiency of the oxygenator decreased from 76,9% to 49,5%. For simulation reasons, the relation between the pCO2(i) and outlet (pCO2(o)) for each oxygenator at different blood and gas flows, was described as an exponential formula. Conclusion: The performance of an oxygenator in terms of CO2 elimination depends not only on the blood and gas flow, but also on the initial pCO2 value. This dependence is crucial for simulation studies in the future. [ABSTRACT FROM AUTHOR]

The hollow fiber membrane bundle is the functional component of artificial lungs, transferring oxygen to and carbon dioxide from the blood. It is also the primary location of blood clot formation and propagation in these devices. The geometric design of fiber bundles is defined by a narrow set of parameters that determine gas exchange efficiency and blood flow resistance, principally: fiber packing density, path length, and frontal area. These same parameters also affect thrombosis. This study investigated the effect of these parameters on clot formation using 3D printed flow chambers that mimic the geometry and blood flow patterns of fiber bundles. Hollow fibers were represented by an array of vertical micro‐rods (380 μm diameter) arranged with three packing densities (40%, 50%, and 60%) and two path lengths (2 and 4 cm). Blood was pumped through these devices corresponding to three mean blood flow velocities (16, 20, and 25 cm/min). Results showed that (1) clot formation decreases dramatically with decreasing packing density and increasing blood flow velocity, (2) clot formation at the outlet of the fiber bundle enhances deposition upstream, and consequently (3) greater path length provides greater clot‐free fiber surface area for gas exchange than a shorter path length. These results can help guide the design of less thrombogenic, more efficient artificial lung designs. [ABSTRACT FROM AUTHOR]

Background: Nitric oxide (NO) is a strong vasodilator, selectively directed on pulmonary circulation through inhaled administration. In adult intensive care units (ICU), it is mainly used for refractory hypoxemia in mechanically ventilated patients. Several medical delivery devices have been developed to deliver inhaled nitric oxide (iNO). The main purpose of those devices is to guarantee an accurate inspiratory NO concentration, whatever the ventilator used, with NO2 concentrations lower than 0.3 ppm. We hypothesized that the performances of the different available iNO delivery systems could depend on their working principle and could be influenced by the ventilator settings. The objective of this study was to assess the accuracy of seven different iNO-devices combined with different ICU ventilators' flow-by to reach inspiratory NO concentration targets and to evaluate their potential risk of toxicity. Methods: We tested seven iNO-devices on a test-lung connected to distinct ICU ventilators offering four different levels of flow-by. We measured the flow in the inspiratory limb of the patient circuit and the airway pressure. The nitric oxide/nitrogen (NO/N2) flow was measured on the administration line of the iNO-devices. NO and NO2 concentrations were measured in the test-lung using an electrochemical analyzer. Results: We identified three iNO-device generations based on the way they deliver NO flow: "Continuous", "Sequential to inspiratory phase" (I-Sequential) and "Proportional to inspiratory and expiratory ventilator flow" (Proportional). Median accuracy of iNO concentration measured in the test lung was 2% (interquartile range, IQR -19; 36), -23% (IQR -29; -17) and 0% (IQR -2; 0) with Continuous, I-Sequential and Proportional devices, respectively. Increased ventilator flow-by resulted in decreased iNO concentration in the test-lung with Continuous and I-Sequential devices, but not with Proportional ones. NO2 formation measured to assess potential risks of toxicity never exceeded the predefined safety target of 0.5 ppm. However, NO2 concentrations higher than or equal to 0.3 ppm, a concentration that can cause bronchoconstriction, were observed in 19% of the different configurations. Conclusion: We identified three different generations of iNO-devices, based on their gas administration modalities, that were associated with highly variable iNO concentrations' accuracy. Ventilator's flow by significantly impacted iNO concentration. Only the Proportional devices permitted to accurately deliver iNO whatever the conditions and the ventilators tested. [ABSTRACT FROM AUTHOR]

Mechanical loads on the polymeric fibers of oxygenating bundles are commonly present due to bundle press-fitting during device assembly and blood pressure load. However, computational fluid dynamics (CFD) simulations for fiber bundle optimization neglect possible changes in microstructure due to such deformations. The aim of this study is to investigate the impact of fiber deformability on bundle microstructure and fluid dynamics mainly in terms of permeability. Fibers from commercial mats typically used for blood oxygenators were mechanically tested and based on these experimental data, a material model was developed to simulate the structural deformations the fibers undergo under press-fitting and blood pressure loads. Then, CFD simulations were performed on deformed bundle repetitive units to investigate permeability under varying loading conditions. The effects of different bundle geometric parameters on the variation of bundle permeability due to press-fitting were evaluated. Bundle press-fitting results in significant changes in microstructure that are reflected in a bundle permeability more than halved for a 15% press-fitting. This impact on permeability is present in all the simulated fiber bundles and becomes more pronounced as the pitch between fibers and thus bundle porosity decreases. Instead, the analyses on pressurized bundle show only small deformations caused by pressure load, with permeability changes below 1%. While blood pressure effects could be neglected, bundle press-fitting turns out to have a significant impact on bundle microstructure and permeability. Neglecting such microstructure variations during CFD simulations could also lead to incorrect assessment of the local fluid dynamics within the bundle. [ABSTRACT FROM AUTHOR]

Blood oxygenators are used to saturate oxygen levels and remove carbon dioxide from the body during cardiopulmonary bypass. Although the natural lung is hydrophilic, commercially used oxygenator materials are hydrophobic. Surface hydrophobicity weakens blood compatibility, as long‐term contact with the blood environment may lead to different degrees of blood activity. Polysulfone may be considered an alternative hydrophilic material in the design of oxygenators. Therefore, it may be directed toward developing hydrophilic membranes. This study aims to investigate the feasibility of achieving blood gas transfer with a polysulfone‐based microporous hollow fiber membrane and compare it with the commercially available polypropylene membranes. Structural differences in the membrane morphology, surface hydrophilicity, tortuosity, mass transfer rate, and material properties under different operation conditions of temperature and flow rates are reported. The polysulfone membrane has a water contact angle of 81.3°, whereas a commercial polypropylene membrane is 94.5°. The mass transfer resistances (s/m) for the polysulfone and polypropylene membranes are calculated to be 4.8 × 104 and 1.5 × 104 at 25°C, respectively. The module made of polysulfone was placed in the cardiopulmonary bypass circuit in parallel with the commercial oxygenator, and pH, pO2, pCO2 levels, and metabolic activity were measured in blood samples. [ABSTRACT FROM AUTHOR]

We demonstrate a methodology which both improves oxygen transport and reduces or eliminates bubble formation in a novel hyperbaric membrane oxygenator catheter model system. Angular oscillations were introduced to a bundle of hollow fiber membranes (HFMs) supplied with hyperbaric 100% oxygen at average gauge pressures up to 0.35 barg. Oscillating bundles enabled delivery of an oxygen flux of up to 400 mL min−1 m−2 in an aqueous solution, a doubling over a previous non-oscillating setup. Similarly, the addition of angular oscillations facilitated a five-fold reduction in pressure to achieve similar oxygen flux. The increased angular speed of oscillation improved flux, while the addition of angular micro-oscillation variations resulted in flux reductions of 7–20% compared to continuous macro-oscillation only, depending on mixing conditions. However, semi-quantitative visual observation demonstrated that angular oscillations reduced or eliminated the instance of oxygen bubble formation on the HFMs. The modeled mass transfer coefficients indicated a quasi linear relationship between rotational velocity and flux, suggesting that faster oscillation speeds could further improve oxygen mass transport allowing for HFM bundles to maintain high oxygen fluxes while eliminating bubble formation. This encourages further development of our compact oxygenating catheter that could be used intravascularly. [ABSTRACT FROM AUTHOR]

Purpose: Fulminant myocarditis presents as acute severe heart failure and requires mechanical cardiocirculatory support. Left-ventricular (LV) decompression is necessary for the successful recovery of these patients. This retrospective study aimed to evaluate the functional outcomes of providing central extracorporeal membrane oxygenation (ECMO) with LV decompression for the treatment of refractory fulminant myocarditis. Methods: Between January 2015 and February 2021, seven consecutive fulminant myocarditis patients (mean age: 41.1 ± 26.1 years) received central ECMO support with transapical LV decompression, with an 18 French cannula integrated into the ECMO circuit in a Y-fashion. The baseline characteristics and postoperative outcomes of the patients were collected. Results: On admission, all patients received prior peripheral ECMO, and 85.7% (6/7) of patients received prior intra-aortic balloon pumping. However, all patients had refractory cardiogenic shock that failed prior to decompression. Six patients recovered successfully after a mean ECMO support of 20.0 ± 11.5 days and five patients had no recurrence of cardiac decompensation. The mean ICU and mean hospital stays were 36.7 ± 23.5 days and 60.6 ± 24.9 days, respectively. Hospital mortality was 28.6% (2/7). Two patients died due to sepsis and stroke during hospitalization. Conclusions: Central ECMO with an LV vent was effective for fulminant myocarditis refractory to percutaneous cardiopulmonary support therapy and other therapies. [ABSTRACT FROM AUTHOR]

When returning blood to the pulmonary artery (PA), the inflow jet interferes with local hemodynamics. We investigated the consequences for several connection scenarios using transient computational fluid dynamics simulations. The PA was derived from CT data. Three aspects were varied: graft flow rate, anastomosis location, and inflow jet path length from anastomosis site to impingement on the PA wall. Lateral anastomosis locations caused abnormal flow distribution between the left and right PA. The central location provided near-physiological distribution but induced higher wall shear stress (WSS). All effects were most pronounced at high graft flows. A central location is beneficial regarding flow distribution, but the resulting high WSS might promote detachment of local thromboembolisms or influence the autonomic nervous innervation. Lateral locations, depending on jet path length, result in lower WSS at the cost of an unfavorable flow distribution that could promote pulmonary vasculature changes. Case-specific decisions and further research are necessary. [ABSTRACT FROM AUTHOR]

Background: Terminal lung diseases such as chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PH) in progression cause a large reduction in quality of life and may lead to bilateral lung transplantation (bLTx). An artificial portable lung could provide a bridge to lung transplantation, allowing patients to remain at home and mobile for longer. To advance the development of such an artificial lung, patient feedback is essential. The aim of this study is to analyze patient acceptance about an extracorporeal artificial lung and to implement these findings into the development.Methods: In collaboration with a medical device developer, we presented a portable dummy oxygenator to patients with advanced lung disease, as potential end users. Data collection in Germany and France was based on two different methods: an online questionnaire and face-to-face interviews (F2F).Results: A total of 604 participants answered the online questionnaire and 17 participants were included in the F2F interviews. The majority of participants (COPD n=140, PH n=17) were able to walk more than 1 km with a mean suffering pressure of 2.87 and 3, respectively. Six of the 17 F2F participants who could walk < 1 km were interested in an assistive device. The statistical value of Fisher's exact test for suffering pressure and desire for a portable oxygenator was 0.45.Conclusion: In patients with advanced lung disease, there is no statistically significant association between subjectively increased suffering pressure and desire for a portable oxygenator, so market introduction may be difficult. Potential end users should be implemented early in device development. Data collection via an online questionnaire combined with personal interviews has proven to be a successful approach here. [ABSTRACT FROM AUTHOR]

Extracorporeal life support is an advanced therapy that circulates blood through an extracorporeal oxygenator, performing gas exchange outside the body. However, its use is limited by severe complications, including bleeding, clotting, and hemolysis. Semiconductor silicon-based membranes have emerged as an alternative to traditional hollow-fiber semipermeable membranes. These membranes offer excellent gas exchange efficiency and the potential to increase hemocompatibility by improving flow dynamics. In this work, we evaluate two next-generation silicon membrane designs, which are intended to be mechanically robust and efficient in gas exchange, while simultaneously reducing fabrication complexity. The "window" design features 10 µm pores on one side and large windows on the back side. The "cavern" design also uses 10 µm pores but contains a network of interconnected buried caverns to distribute the sweep gas from smaller inlet holes. Both designs were shown to be technically viable and able to be reproducibly fabricated. In addition, they both were mechanically robust and withstood 30 psi of transmembrane pressure without breakage or bubbling. At low sweep gas pressures, gas transfer efficiency was similar, with the partial pressure of oxygen in water increasing by 10.7 ± 2.3 mmHg (mean ± standard deviation) and 13.6 ± 1.9 mmHg for the window and cavern membranes, respectively. Gas transfer efficiency was also similar at higher pressures. At 10 psi, oxygen tension increased by 16.8 ± 5.7 mmHg (window) and 18.9 ± 1.3 mmHg (cavern). We conclude that silicon membranes featuring a 10 µm pore size can simplify the fabrication process and improve mechanical robustness while maintaining excellent efficiency. [ABSTRACT FROM AUTHOR]

The use of extracorporeal oxygenation and CO2 removal has gained clinical validity and popularity in recent years. These systems are composed of a pump to drive blood flow through the circuit and a hollow fiber membrane bundle through which gas exchange is achieved. Mathematical modeling of device design is utilized by researchers to improve device hemocompatibility and efficiency. A previously published mathematical model to predict CO2 removal in hollow fiber membrane bundles was modified to include an empirical representation of the Haldane effect. The predictive capabilities of both models were compared to experimental data gathered from a fiber bundle of 7.9 cm in length and 4.4 cm in diameter. The CO2 removal rate predictions of the model including the Haldane effect reduced the percent error between experimental data and mathematical predictions by up to 16%. Improving the predictive capabilities of computational fluid dynamics for the design of hollow fiber membrane bundles reduces the monetary and manpower expenses involved in designing and testing such devices. [ABSTRACT FROM AUTHOR]

The increasing prevalence of chronic lung disease worldwide, combined with the emergence of multiple pandemics arising from respiratory viruses over the past century, highlights the need for safer and efficacious means for providing artificial lung support. Mechanical ventilation is currently used for the vast majority of patients suffering from acute and chronic lung failure, but risks further injury or infection to the patient's already compromised lung function. Extracorporeal membrane oxygenation (ECMO) has emerged as a means of providing direct gas exchange with the blood, but limited access to the technology and the complexity of the blood circuit have prevented the broader expansion of its use. A promising avenue toward simplifying and minimizing complications arising from the blood circuit, microfluidics‐based artificial organ support, has emerged over the past decade as an opportunity to overcome many of the fundamental limitations of the current standard for ECMO cartridges, hollow fiber membrane oxygenators. The power of microfluidics technology for this application stems from its ability to recapitulate key aspects of physiological microcirculation, including the small dimensions of blood vessel structures and gas transfer membranes. An even greater advantage of microfluidics, the ability to configure blood flow patterns that mimic the smooth, branching nature of vascular networks, holds the potential to reduce the incidence of clotting and bleeding and to minimize reliance on anticoagulants. Here, we summarize recent progress and address future directions and goals for this potentially transformative approach to artificial lung support. Correspondence between native blood vessel branching and the microfluidic blood vessel branching patterns that form the design basis for bio‐inspired artificial organs. As in the physiological vasculature, a large inlet vessel branches into multiple trunk lines, each of which leads to further branching into smaller microchannels. This design paradigm preserves a smooth distribution of blood flow throughout the microfluidic network. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Tissue Engineering Research / Zhongguo Zuzhi Gongcheng Yanjiu is the property of Chinese Journal of Tissue Engineering Research and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: Admixture of nitric oxide (NO) to the gas inspired with mechanical ventilation can be achieved through continuous, timed, or pulsed injection of NO into the inspiratory limb. The dose and timing of NO injection govern the inspired and intrapulmonary effect site concentrations achieved with different administration modes. Here we test the effectiveness and target reliability of a new mode injecting pulsed NO boluses exclusively during early inspiration. Methods: An in vitro lung model was operated under various ventilator settings. Admixture of NO through injection into the inspiratory limb was timed either (i) selectively during early inspiration ("pulsed delivery"), or as customary, (ii) during inspiratory time or (iii) the entire respiratory cycle. Set NO target concentrations of 5–40 parts per million (ppm) were tested for agreement with the yield NO concentrations measured at various sites in the inspiratory limb, to assess the effectiveness of these NO administration modes. Results: Pulsed delivery produced inspiratory NO concentrations comparable with those of customary modes of NO administration. At low (450 ml) and ultra-low (230 ml) tidal volumes, pulsed delivery yielded better agreement of the set target (up to 40 ppm) and inspiratory NO concentrations as compared to customary modes. Pulsed delivery with NO injection close to the artificial lung yielded higher intrapulmonary NO concentrations than with NO injection close to the ventilator. The maximum inspiratory NO concentration observed in the trachea (68 ± 30 ppm) occurred with pulsed delivery at a set target of 40 ppm. Conclusion: Pulsed early inspiratory phase NO injection is as effective as continuous or non-selective admixture of NO to inspired gas and may confer improved target reliability, especially at low, lung protective tidal volumes. [ABSTRACT FROM AUTHOR]

In end-stage lung diseases, the shortage of donor lungs for transplantation and long waiting lists are the main culprits in the significantly increasing number of patient deaths. New strategies to curb this issue are being developed with the help of recent advancements in bioengineering technology, with the generation of lung scaffolds as a steppingstone. There are various types of lung scaffolds, namely, acellular scaffolds that are developed via decellularization and recellularization techniques, artificial scaffolds that are synthesized using synthetic, biodegradable, and low immunogenic materials, and hybrid scaffolds which combine the advantageous properties of materials in the development of a desirable lung scaffold. There have also been advances in the design of bioreactors in terms of providing an optimal regenerative environment for the maturation of functional lung tissue over time. In this review, the emerging paradigms in the field of lung tissue bioengineering will be discussed. [ABSTRACT FROM AUTHOR]

Background: Membranes based on triply periodic minimal surfaces (TPMS) have proven a superior gas transfer compared to the contemporary hollow fiber membrane (HFM) design in artificial lungs. The improved oxygen transfer is attributed to disrupting the laminar boundary layer adjacent to the membrane surface known as main limiting factor to mass transport. However, it requires experimental proof that this improvement is not at the expense of greater damage to the blood. Hence, the aim of this work is a valid statement regarding the structure‐dependent hemolytic behavior of TPMS structures compared to the current HFM design. Methods: Hemolysis tests were performed on structure samples of three different kind of TPMS‐based designs (Schwarz‐P, Schwarz‐D and Schoen's Gyroid) in direct comparison to a hollow fiber structure as reference. Results: The results of this study suggest that the difference in hemolysis between TPMS membranes compared to HFMs is small although slightly increased for the TPMS membranes. There is no significant difference between the TPMS structures and the hollow fiber design. Nevertheless, the ratio between the achieved additional oxygen transfer and the additional hemolysis favors the TPMS‐based membrane shapes. Conclusion: TPMS‐shaped membranes offer a safe way to improve gas transfer in artificial lungs. [ABSTRACT FROM AUTHOR]

Membranes for use in high gas exchange lung applications are riddled with fouling. The goal of this research is to create a membrane that can function in an artificial lung until the actual lung becomes available for the patient. The design of the artificial lung is based on new hollow fiber membranes (HFMs), due to which the current devices have short and limited periods of low fouling. By successfully modifying membranes with attached peptoids, low fouling can be achieved for longer periods of time. Hydrophilic modification of porous polysulfone (PSF) membranes can be achieved gradually by polydopamine (PSU-PDA) and peptoid (PSU-PDA-NMEG5). Polysulfone (PSU-BSA-35Mg), polysulfone polydopamine (PSUPDA-BSA-35Mg) and polysulfone polydopamine peptoid (PSU-PDA-NMEG5-BSA35Mg) were tested by potting into the new design of gas exchange modules. Both surfaces of the modified membranes were found to be highly resistant to protein fouling permanently. The use of different peptoids can facilitate optimization of the low fouling on the membrane surface, thereby allowing membranes to be run for significantly longer time periods than has been currently achieved. [ABSTRACT FROM AUTHOR]

Artificial lung technology is advancing at a startling rate raising hopes that it would better serve the needs of those requiring respiratory support. Whether to assist the healing of an injured lung, support patients to lung transplantation, or to entirely replace native lung function, safe and effective artificial lungs are sought. After 200 years of bioengineering progress, artificial lungs are closer than ever before to meet this demand which has risen exponentially due to the COVID-19 crisis. In this review, the critical advances in the historical development of artificial lungs are detailed. The current state of affairs regarding extracorporeal membrane oxygenation, intravascular lung assists, pump-less extracorporeal lung assists, total artificial lungs, andmicrofluidic oxygenators are outlined. [ABSTRACT FROM AUTHOR]

Lung transplantation may be a final destination therapy in lung failure, but limited donor organ availability creates a need for alternative management, including artificial lung technology. This invited review discusses ongoing developments and future research pathways for respiratory assist devices and tissue engineering to treat advanced and refractory lung disease. An overview is also given on the aftermath of the coronavirus disease 2019 pandemic and lessons learned as the world comes out of this situation. The first order of business in the future of lung support is solving the problems with existing mechanical devices. Interestingly, challenges identified during the early days of development persist today. These challenges include device‐related infection, bleeding, thrombosis, cost, and patient quality of life. The main approaches of the future directions are to repair, restore, replace, or regenerate the lungs. Engineering improvements to hollow fiber membrane gas exchangers are enabling longer term wearable systems and can be used to bridge lung failure patients to transplantation. Progress in the development of microchannel‐based devices has provided the concept of biomimetic devices that may even enable intracorporeal implantation. Tissue engineering and cell‐based technologies have provided the concept of bioartificial lungs with properties similar to the native organ. Recent progress in artificial lung technologies includes continued advances in both engineering and biology. The final goal is to achieve a truly implantable and durable artificial lung that is applicable to destination therapy. [ABSTRACT FROM AUTHOR]

Purpose: Currently used cannulae for extracorporeal carbon dioxide removal (ECCO2R) are associated with complications such as thrombosis and distal limb ischemia, especially for long-term use. We hypothesize that the risk of these complications is reducible by attaching hemodynamically optimized grafts to the patient's vessels. In this study, as a first step towards a long-term stable ECCO2R connection, we investigated the feasibility of a venovenous connection to the common iliac veins. To ensure its applicability, the drainage of reinfused blood (recirculation) and high wall shear stress (WSS) must be avoided. Methods: A reference model was selected for computational fluid dynamics, on the basis of the analysis of imaging data. Initially, a sensitivity analysis regarding recirculation was conducted using as variables: blood flow, the distance of drainage and return to the iliocaval junction, as well as the diameter and position of the grafts. Subsequently, the connection was optimized regarding recirculation and the WSS was evaluated. We validated the simulations in a silicone model traversed by dyed fluid. Results: The simulations were in good agreement with the validation measurements (mean deviation 1.64%). The recirculation ranged from 32.1 to 0%. The maximum WSS did not exceed 5.57 Pa. The position and diameter of the return graft show the highest influence on recirculation. A correlation was ascertained between recirculation and WSS. Overall, an inflow jet directed at a vessel wall entails not only high WSS, but also a flow separation and thereby an increased recirculation. Therefore, return grafts aligned to the vena cava are crucial. Conclusion: In conclusion, a connection without recirculation could be feasible and therefore provides a promising option for a long-term ECCO2R connection. [ABSTRACT FROM AUTHOR]

Extracorporeal membrane oxygenation (ECMO) has become a mainstay of therapy for patients suffering from severe respiratory failure. Ambulatory ECMO systems aim to provide long‐term out‐of‐hospital respiratory support. As a patient's activity level changes, the required level of ECMO support varies with oxygen consumption and metabolic fluctuations. To compensate for such changes, an autoregulatory ECMO system (AR‐ECMO) has been developed and its performance was evaluated as a proof of concept in an acute ovine model. The AR‐ECMO system consists of a regular ECMO circuit and an electromechanical control system. A custom fuzzy logic control algorithm was implemented to adjust the blood flow and sweep gas flow of the ECMO circuit to meet the varying respiratory demand by utilizing two noninvasive sensors for venous oxyhemoglobin saturation and the oxygenator exhaust gas CO2 concentration. Disturbance responses of the AR‐ECMO to induced acute respiratory distress were assessed for six hours in four juvenile sheep cannulated with a veno‐pulmonary artery ECMO configuration, including acute ventilator shutoff, ventilator step change (off‐on‐off), and forced desaturation. All sheep survived for the study duration. The AR‐ECMO system was able to respond and maintain stable hemodynamics and physiological blood gas contents (SpO2 = 96.3 % ± 4.29, pH 7.44 ± 0.09, pCO2 = 38.9 ± 9.9 mm Hg, and pO2 =237.9 ± 123.6 mm Hg) during simulated respiratory distress. Acceptable correlation between oxygenator exhaust gas CO2 and oxygenator outlet pCO2 were observed (R2 = 0.84). In summary, the AR‐ECMO system successfully maintained physiologic control of peripheral oxygenation and carbon dioxide over the study period, utilizing only measurements taken directly from the ECMO circuit. The range of system response necessitates an adaptable system in the setting of variable metabolic demands. The ability of this system to respond to significant disturbances in ventilator support is encouraging. Future work to evaluate our AR‐ECMO system in long‐term, awake animal studies is necessary for further refinement. [ABSTRACT FROM AUTHOR]

Veno-venous extracorporeal membrane oxygenation (VV-ECMO) has emerged as a potential life-saving treatment for patients with acute respiratory failure. Given the accumulating literature supporting the use of VV-ECMO without therapeutic levels of anticoagulation, it might be feasible to use it for planned intubation before surgical procedures. Here, we report consecutive series of patients who underwent planned initiation of VV-ECMO, without anticoagulation, before induction of general anesthesia for anticipated difficult airways or respiratory decompensation. We describe the approach to safely initiate VV-ECMO in an awake patient. We retrospectively identified patients in a prospectively maintained database who underwent planned initiation of VVECMO before intubation. Standard statistical methods were used to determine post-procedure outcomes. Patients included were three men and one woman, with a mean age of 34.3 6 10.4 years. Indications included mediastinal lymphoma, foreign body obstruction, hemoptysis, and tracheo-esophageal fistula. VV-ECMO was initiated electively for all patients, and no anticoagulation was used. The median duration of VV-ECMO support was 2.5 days (1-11 days), the median length of ventilator dependence and intensive care unit stay was 1 day (1-23 days) and 5 days (4-31 days), respectively. The median length of stay was 18.5 days (8-39 days). There were no thrombotic complications and no mortality at 30 days. Initiation of awake VV-ECMO is feasible and is safe before intubation and induction of anesthesia in patients at high risk for respiratory decompensation. [ABSTRACT FROM AUTHOR]

In the concept of a biohybrid lung, endothelial cells seeded on gas exchange membranes form a non-thrombogenic an anti-inflammatory surface to overcome the lacking hemocompatibility of today's oxygenators during extracorporeal membrane oxygenation. To evaluate this concept, the long-term stability and gas exchange performance of endothelialized RGD-conjugated polydimethylsiloxane (RGD-PDMS) membranes was evaluated. Human umbilical vein endothelial cells (ECs) were cultured on RGD-PDMS in a model system under physiological wall shear stress (WSS) of 0.5 Pa for up to 33 days. Gas exchange performance was tested with three biological replicates under elevated WSS of 2.5 Pa using porcine blood adjusted to venous values following ISO 7199 and blood gas analysis. EC morphology was assessed by immunocytochemistry (n = 3). RGD-PDMS promoted endothelialization and stability of endothelialized membranes was shown for at least 33 days and for a maximal WSS of 2.5 Pa. Short-term exposure to porcine blood did not affect EC integrity. The gas transfer tests provided evidence for the oxygenation and decarboxylation of the blood across endothelialized membranes with a decrease of transfer rates over time that needs to be addressed in further studies with larger sample sizes. Our results demonstrate the general suitability of RGD-PDMS for biohybrid lung applications, which might enable long-term support of patients with chronic lung failure in the future. [ABSTRACT FROM AUTHOR]

We developed a novel system comprising acid infusion, membrane lung, and a continuous renal replacement therapy console for efficient CO2 removal at a low blood flow. To evaluate the new system, we used an ex vivo experimental model using swine blood. A liter of aliquoted blood adjusted to pH 7.25 and pCO2 65 mm Hg was mixed with acid (0, 10, or 20 mL of lactic or hydrochloric acid [1 mol/L]) and was immediately delivered to the system in a single pass. We collected blood samples at each point of the circuit and calculated the amount of CO2 eliminated by the membrane lung. The new system removed 13.2 ± 0.8, 32.0 ± 2.1, and 51.6 ± 3.7 mL/min of CO2 (with 0, 10, and 20 mEq/L of lactic acid) and 21.2 ± 1.2, 27.3 ± 0.3, and 42.0 ± 1.3 mL/min (with 0, 10, and 20 mEq/L of hydrochloric acid), respectively. The levels of lactate and Cl− ions for acid-base equilibrium were restored after continuous hemodiafiltration. Thus, the amount of CO2 eliminated by the membrane lung was 3.9 times higher with lactic acid and 2.0 times higher with hydrochloric acid compared with non-acid controls. In conclusion, this easy-to-setup CO2 removal system was safe, effective, and removed CO2 at a low blood flow. [ABSTRACT FROM AUTHOR]

Abstract: Under physiological conditions, up to 97% of the oxygen in blood that is transported from lungs to tissue is bound to hemoglobin. To predict oxygen transfer in artificial lungs on a membrane fiber level with computational fluid dynamics (CFD), previous investigators have incorporated the hemoglobin‐oxygen interaction into an effective diffusivity coefficient to modify the convection‐diffusion equation. Based on our own simulations and experiments, these approaches tend to significantly overestimate the oxygen transfer. The present study introduces a novel approach to model the oxygen transfer in blood on a fiber level with CFD. Plasma and red blood cells were implemented as two phases and the reaction of hemoglobin and oxygen to oxyhemoglobin was included in the convection‐diffusion equation in form of a source term. The model was implemented with the commercial software Ansys CFX 18.1. CFD simulations were compared with in vitro experiments on three micro oxygenators with a staggered fiber configuration under multiple blood flow conditions. To calibrate the model, a reaction rate R0 was introduced and experimental data was fitted to a blood flow of 50 mL/h. Our model approximated the oxygen transfer rates with a difference, relative to in vitro results, of −23.7 and +6.3% for blood flows of 20 and 90 mL/h, respectively. The effective diffusivity model, used by previous authors, was implemented for comparison and approximated oxygen transfer rates with a difference, relative to in vitro data, of +13.7, +68.8, and +121.0% for blood flows of 20, 50, and 90 mL/h, respectively. A well‐established numerical mass transfer correlation approximated the gas transfer with a difference, referenced on the average in vitro data, of 31.8, 13.1, and 5.0% for blood flows of 20, 50, and 90 mL/h, respectively. Even though results are promising, a thorough validation of the model will require extensive CFD and in vitro studies of multiple fiber arrangements, fiber diameters, and therefore fiber bundle porosities in the future. This article should be understood as a first feasibility study to evaluate the potential of the novel oxygen transfer model. [ABSTRACT FROM AUTHOR]

For the patients with progressively decompensating acute or acute-on-chronic respiratory failure, the first-choice treatment remains as mechanical ventilation. Despite the consistent value of mechanical ventilation, the majority of lung specialists are aware of its limitations, in particular for the patients with advanced lung failure, and inherent drawbacks that augment disease progression. More recently, the concept of allowing the lungs to ‘rest and recover’ has been supported by quite a few clinical studies. The pressure and volume of gas delivered to the lungs are reduced compared with mechanical ventilation. Based on recent remarkable evidence and experiences using extracorporeal lung support (ECLS) before, during and after lung transplant, there is growing interest in and expectations for the use of ECLS beyond lung transplant to encompass the entire field of pulmonary medicine. The purpose of this review article is to provide an update on evolving ECLS technologies and their effectiveness and discuss the future of ECLS for advanced lung failure as a new subspecialty in cardiothoracic surgery. [ABSTRACT FROM AUTHOR]

Polyethylene glycol (PEG) and heparin (Hep) were grafted onto polysulfone (PSF) membrane by plasma-induced surface modification to prepare PSF-PEG-Hep membranes used for artificial lung. The effects of plasma treatment parameters, including power, gas type, gas flow rate, and treatment time, were investigated, and different PEG chains were bonded covalently onto the surface in the postplasma grafting process. Membrane surfaces were characterized by water contact angle, PEG grafting degree, attenuated total reflectance-Fourier transform infrared spectroscopy, ultraviolet-visible spectrophotometry, X-ray photoelectron spectroscopy, critical water permeability pressure, and scanning electron microscopy. Protein adsorption, platelet adhesion, and coagulation tests showed significant improvement in the hemocompatibility of PSF-PEG-Hep membranes compared to pristine PSF membrane. Gas exchange tests through PSF-PEG6000-Hep membrane showed that when the flow rate of porcine blood reached 5.0 L/min, the permeation fluxes of O2 and CO2 reached 192.6 and 166.9 mL/min, respectively, which were close to the gas exchange capacity of a commercial membrane oxygenator. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1737-1746, 2017. [ABSTRACT FROM AUTHOR]

Background: Extracorporeal carbon dioxide removal (ECCOR) systems have gained clinical appeal as supplemental therapy in the treatment of acute and chronic respiratory injuries with low tidal volume or non-invasive ventilation. We have developed an ultra-low-flow ECCOR device (ULFED) capable of operating at blood flows comparable to renal hemodialysis (250 mL/min). Comparable operating conditions allow use of minimally invasive dialysis cannulation strategies with potential for direct integration to existing dialysis circuitry. Methods: A carbon dioxide (CO) removal device was fabricated with rotating impellers inside an annular hollow fiber membrane bundle to disrupt blood flow patterns and enhance gas exchange. In vitro gas exchange and hemolysis testing was conducted at hemodialysis blood flows (250 mL/min). Results: In vitro carbon dioxide removal rates up to 75 mL/min were achieved in blood at normocapnia (pCO = 45 mmHg). In vitro hemolysis (including cannula and blood pump) was comparable to a Medtronic Minimax oxygenator control loop using a time-of-therapy normalized index of hemolysis (0.19 ± 0.04 g/100 min versus 0.12 ± 0.01 g/100 min, p = 0.169). Conclusions: In vitro performance suggests a new ultra-low-flow extracorporeal CO removal device could be utilized for safe and effective CO removal at hemodialysis flow rates using simplified and minimally invasive connection strategies. [ABSTRACT FROM AUTHOR]

Respiratory failure is one of the major causes of mortality and morbidity all over the world. Therapeutic options to treat respiratory failure remain limited. The objective of this study was to evaluate the gas transfer performance of a newly developed miniature portable integrated pediatric pump-lung device (PediPL) with small membrane surface for respiratory support in an acute ovine respiratory failure model. The respiratory failure was created in six adult sheep using intravenous anesthesia and reduced mechanical ventilation at 2 breaths/min. The PediPL device was surgically implanted and evaluated for respiratory support in a venovenous configuration between the right atrium and pulmonary artery. The hemodynamics and respiratory status of the animals during support with the device gas transfer performance of the PediPL were studied for 4 h. The animals exhibited respiratory failure 30 min after mechanical ventilation was reduced to 2 breaths/min, indicated by low oxygen partial pressure, low oxygen saturation, and elevated carbon dioxide in arterial blood. The failure was reversed by establishing respiratory support with the PediPL after 30 min. The rates of O2 transfer and CO2 removal of the PediPL were 86.8 and 139.1 mL/min, respectively. The results demonstrated that the PediPL (miniature integrated pump-oxygenator) has the potential to provide respiratory support as a novel treatment for both hypoxia and hypercarbia. The compact size of the PediPL could allow portability and potentially be used in many emergency settings to rescue patients suffering acute lung injury. [ABSTRACT FROM AUTHOR]

Computational fluid dynamics (CFD) is used to simulate blood flow inside the fiber bundles of oxygenators. The results are interpreted in terms of flow distribution, e.g., stagnation and shunt areas. However, experimental measurements that provide such information on the local flow between the fibers are missing. A transparent model of an oxygenator was built to perform particle image velocimetry (PIV), to perform the experimental validation. The similitude theory was used to adjust the size of the PIV model to the minimal resolution of the PIV system used (scale factor 3.3). A standard flow of 80 mL/min was simulated with CFD for the real oxygenator and the equivalent flow of 711 mL/min, according to the similitude theory, was investigated with PIV. CFD predicts the global size of stagnation and shunt areas well, but underestimates the streamline length and changes in velocities due to the meandering flow around the real fibers in the PIV model. Symmetrical CFD simulation cannot consider asymmetries in the flow, due to manufacturing-related asymmetries in the fiber bundle. PIV could be useful for validation of CFD simulations; measurement quality however must be improved for a quantitative validation of CFD results and the investigation of flow effects such as tortuosity and anisotropic flow behavior. [ABSTRACT FROM AUTHOR]

Introduction or background The incidence of chronic lung disease is increasing worldwide due to the spread of risk factors and ageing population. An important advance in treatment would be the development of a bioartificial lung where the blood–gas exchange surface is manufactured from a synthetic or natural scaffold material that is seeded with the appropriate stem or progenitor cells to mimic the functional tissue of the natural lung. Sources of data Articles relating to bioartificial lungs were sourced through PubMed and ISI Web of Knowledge. Areas of agreement There is a consensus that advances in bioartificial lung engineering will be beneficial to patients with chronic lung failure. Ultimate success will require the concerted efforts of researchers drawn from a broad range of disciplines, including clinicians, cell biologists, materials scientists and engineers. Areas of controversy As a source of cells for use in bioartificial lungs it is proposed to use human embryonic stem cells; however, there are ethical and safety concerns regarding the use of these cells. Growing points There is a need to identify the optimum strategies for differentiating progenitor cells into functional lung cells; a need to better understand cell-biomaterial/ECM interactions and a need to understand how to harness the body's natural capacity to regenerate the lung. Areas timely for developing research Biomaterial technologies for recreating the natural lung ECM and architecture need further development. Mathematical modelling techniques should be developed for determining optimal scaffold seeding strategies and predicting gas exchange performance. [ABSTRACT FROM PUBLISHER]

Hollow fiber artificial lungs are increasingly being used for long-term applications. However, clot formation limits their use to 1-2 weeks. This study investigated the effect of nitric oxide generating (NOgen) hollow fibers on artificial lung thrombogenicity. Silicone hollow fibers were fabricated to incorporate 50 nm copper particles as a catalyst for NO generation from the blood. Fibers with and without (control) these particles were incorporated into artificial lungs with a 0.1 m2 surface area and inserted in circuits coated tip-to-tip with the NOgen material. Circuits ( N = 5/each) were attached to rabbits in a pumpless, arterio-venous configuration and run for 4 h at an activated clotting time of 350-400 s. Three control circuits clotted completely, while none of the NOgen circuits failed. Accordingly, blood flows were significantly higher in the NOgen group (95.9 ± 11.7, p < 0.01) compared to the controls (35.2 ± 19.7; mL/min), and resistance was significantly higher in the control group after 4 h (15.38 ± 9.65, p < 0.001) than in NOgen (0.09 ± 0.03; mmHg/mL/min). On the other hand, platelet counts and plasma fibrinogen concentration expressed as percent of baseline in control group (63.7 ± 5.7%, 77.2 ± 5.6%; p < 0.05) were greater than those in the NOgen group (60.4 ± 5.1%, 63.2 ± 3.7%). Plasma copper levels in the NOgen group were 2.8 times baseline at 4 h (132.8 ± 4.5 μg/dL) and unchanged in the controls. This study demonstrates that NO generating gas exchange fibers could be a potentially effective way to control coagulation inside artificial lungs. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A: 3511-3519, 2013. [ABSTRACT FROM AUTHOR]

Computational fluid dynamics (CFD) is a useful tool in characterizing artificial lung designs by providing predictions of device performance through analyses of pressure distribution, perfusion dynamics, and gas transport properties. Validation of numerical results in membrane oxygenators has been predominantly based on experimental pressure measurements with little emphasis placed on confirmation of the velocity fields due to opacity of the fiber membrane and limitations of optical velocimetric methods. Biplane X-ray digital subtraction angiography was used to visualize flow of a blood analogue through a commercial membrane oxygenator at 1-4.5 L/min. Permeability and inertial coefficients of the Ergun equation were experimentally determined to be 180 and 2.4, respectively. Numerical simulations treating the fiber bundle as a single momentum sink according to the Ergun equation accurately predicted pressure losses across the fiber membrane, but significantly underestimated velocity magnitudes in the fiber bundle. A scaling constant was incorporated into the numerical porosity and reduced the average difference between experimental and numerical values in the porous media regions from 44 ± 4% to 6 ± 5%. [ABSTRACT FROM AUTHOR]

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Microfabrication techniques are attractive for constructing artificial lungs due to the ability to create features similar in size to those in the natural lung. However, a simple and intuitive mathematical model capable of accurately predicting the gas exchange performance of microchannel artificial lungs does not currently exist. Such a model is critical to understanding and optimizing these devices. Here, we describe a simple, closed-form mathematical model for gas exchange in microchannel artificial lungs and qualify it through application to experimental data from several research groups. We utilize lumped parameters and several assumptions to obtain a closed-form set of equations that describe gas exchange. This work is intended to augment computational models by providing a more intuitive, albeit potentially less accurate, understanding of the operation and trade-offs inherent in microchannel artificial lung devices. [ABSTRACT FROM AUTHOR]

Extracorporeal membrane oxygenation (ECMO) is a well-established therapy for several lung and heart diseases in the field of neonatal and pediatric medicine (e.g., acute respiratory distress syndrome, congenital heart failure, cardiomyopathy). Current ECMO systems are typically composed of an oxygenator and a separate nonpulsatile blood pump. An oxygenator with an integrated pulsatile blood pump for small infant ECMO was developed, and this novel concept was tested regarding functionality and gas exchange rate. Pulsating silicone tubes (STs) were driven by air pressure and placed inside the cylindrical fiber bundle of an oxygenator to be used as a pump module. The findings of this study confirm that pumping blood with STs is a viable option for the future. The maximum gas exchange rate for oxygen is 48 mL/min/L at a medium blood flow rate of about 300 mL/min. Future design steps were identified to optimize the flow field through the fiber bundle to achieve a higher gas exchange rate. First, the packing density of the hollow-fiber bundle was lower than commercial oxygenators due to the manual manufacturing. By increasing this packing density, the gas exchange rate would increase accordingly. Second, distribution plates for a more uniform blood flow can be placed at the inlet and outlet of the oxygenator. Third, the hollow-fiber membranes can be individually placed to ensure equal distances between the surrounding hollow fibers. [ABSTRACT FROM AUTHOR]

Hollow fiber membrane (HFM)-based artificial lungs can require a large blood-contacting membrane surface area to provide adequate gas exchange. However, such a large surface area presents significant challenges to hemocompatibility. One method to improve carbon dioxide (CO2) transfer efficiency might be to immobilize carbonic anhydrase (CA) onto the surface of conventional HFMs. By catalyzing the dehydration of bicarbonate in blood, CA has been shown to facilitate diffusion of CO2 toward the fiber membranes. This study evaluated the impact of surface modifying a commercially available microporous HFM-based artificial lung on fiber blood biocompatibility. A commercial poly(propylene) Celgard HFM surface was coated with a siloxane, grafted with amine groups, and then attached with CA which has been shown to facilitate diffusion of CO2 toward the fiber membranes. Results following acute ovine blood contact indicated no significant reduction in platelet deposition or activation with the siloxane coating or the siloxane coating with grafted amines relative to base HFMs. However, HFMs with attached CA showed a significant reduction in both platelet deposition and activation compared with all other fiber types. These findings, along with the improved CO2 transfer observed in CA modified fibers, suggest that its incorporation into HFM design may potentiate the design of a smaller, more biocompatible HFM-based artificial lung. [ABSTRACT FROM AUTHOR]

Respiratory assist using intravenous catheters may be a potential therapy for patients with acute and acute-on-chronic lung failure. An important design constraint is respiratory catheter size, and new strategies are needed that enable size reduction while maintaining adequate gas exchange. Our group is currently developing a percutaneous respiratory assist catheter (PRAC) that uses a rotating bundle of hollow fiber membranes to enhance CO2 removal and O2 supply with increasing bundle rotation rate. In this study, particle image velocimetry (PIV) was used to analyze the fluid flow patterns and velocity fields surrounding the rotating fiber bundle of the PRAC. The goal of the study was to assess the rotational flow patterns within the context of the gas exchange enhancement that occurs with increasing fiber bundle rotation. A PRAC prototype was placed in a 1-in. internal diameter test section of an in vitro flow loop designed specifically for PIV studies. The rotation rate of the PRAC was varied between 500 and 7000 rpm, and PIV was used to determine the velocity fields in the primary ( r-θ) and secondary ( r- z) flow planes. The secondary flow exhibited time-varying and incoherent vortices that were consistent with the classical Taylor vortices expected for Taylor numbers (Ta) corresponding to the rotation speeds studied (2200 < Ta < 31 000). In the primary flow, the tangential velocity exhibited boundary layers of less than ½ mm adjacent to the fiber bundle and vessel wall. The estimated shear stress associated with the Taylor vortices was approximately 11 dyne/cm2 at 7000 rpm and was over 10 times smaller than the shear stress in the primary flow boundary layers. [ABSTRACT FROM AUTHOR]

We have utilized soft lithography techniques to create three-dimensional arrays of blood microchannels and gas pathways in poly(dimethylsiloxane) (PDMS) that approach the microvascular scale of the natural lung. The blood microchannels were lined with endothelial cells in an effort to provide a non-thrombogenic surface that might ultimately reduce the need for systemic anticoagulation. A novel design and fabrication method were developed to create prototype modules for gas permeance and cell culture testing. The gas permeance modules contained 6 layers, four gas and two blood, while the modules for cell culture testing contained two layers of blood channels. The gas permeance of the modules was examined and maximum values of 9.16 × 10−6 and 3.55 × 10−5 mL/s/cm2/cmHg, for O2 and CO2 respectively, were obtained. Finally, endothelial cells were seeded and dynamically cultured in prototype cell culture modules. Confluent and viable cell monolayers were achieved after 10 days of perfusion. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the effect of multiple mechanical forces in gas exchange and hemolysis in an intravascular lung assist device (IVLAD). Specific focus was given to the effect of membrane vibration. We designed the oscillatory type artificial lung assist device attached with a polyvinylidene fluoride sensor and a lead zirconate titanate (PZT) actuator (vibrator). Maximum oxygen transfer occurred at a frequency of 7 Hz for bovine blood and 35 Hz for distilled water. The normalized index of hemolysis oxygenator values for the circuit was 0.0014 g/mL for excitation of the PZT actuator with a sinusoidal 10-V wave and 0.0018 g/mL for a 50-V wave. The experiment results indicate effective performance in enhancing the gas transfer of the IVLAD. This novel hollow membrane filter IVLAD design demonstrates an acceptable level of gas exchange performance with an acceptable level of blood compatibility, and so it has potential as an implantable lung assist device for patients with acute respiratory distress syndrome. [ABSTRACT FROM AUTHOR]

This article describes recent progress in the field of artificial lungs, centering on the current state and trends in clinical use and research and development. Trends in the recent clinical use in Japan can be found in shipment-number-based surveys as well as in the questionnaire surveys for clinical extracorporeal membrane oxygenation (ECMO) and percutaneous cardiopulmonary support (PCPS). It is likely that the use of artificial lungs for open-heart surgery has peaked, and this can be attributed to the rapid expansion and popularization of off-pump coronary artery bypass grafting surgery. In contrast, the increase in the number of artificial lungs used in assisted circulation cases is showing significant growth. Along with such clinical trends, research and development toward next-generation systems is active in the field of assisted circulation, focusing on emergency or long-term use of PCPS or ECMO. Approaches include enhancing the performance of conventional systems in terms of long-term durability and hemocompatibility, developing a novel device by integrating the oxygenator with the blood pump, and developing an implantable type of artificial lung such as an intravenous oxygenator. Next-generation devices not only will benefit a multitude of patients but also represent an important target with the prospect for expansion of the market for artificial lungs. In the future, further expansion of research and development in this field, as well as progress in practical and clinical applications of innovative devices, is expected. [ABSTRACT FROM AUTHOR]

The analyses performed in this paper reveal that a breathing thermal manikin with realistic simulation of respiration including breathing cycle, pulmonary ventilation rate, frequency and breathing mode, gas concentration, humidity and temperature of exhaled air and human body shape and surface temperature is sensitive enough to perform reliable measurement of characteristics of air as inhaled by occupants. The temperature, humidity, and pollution concentration in the inhaled air can be measured accurately with a thermal manikin without breathing simulation if they are measured at the upper lip at a distance of <0.01 m from the face. Body surface temperature, shape and posture as well as clothing insulation have impact on the measured inhaled air parameters. Proper simulation of breathing, especially of exhalation, is needed for studying the transport of exhaled air between occupants. A method for predicting air acceptability based on inhaled air parameters and known exposure–response relationships established in experiments with human subjects is suggested. Practical Implications Recommendations for optimal simulation of human breathing by means of a breathing thermal manikin when studying pollution concentration, temperature and humidity of the inhaled air as well as the transport of exhaled air (which may carry infectious agents) between occupants are outlined. In order to compare results obtained with breathing thermal manikins, their nose and mouth geometry should be standardized. [ABSTRACT FROM AUTHOR]

To treat acute lung failure, an intravenous membrane gas exchange device, the Hattler Catheter, is currently under development. Several methods were employed to evaluate the biocompatibility of the device during preclinical testing in bovines, and potential coatings for the fibers comprising the device were screened for their effectiveness in reducing thrombus deposition in vitro. Flow cytometric analysis demonstrated that the device had the capacity to activate platelets as evidenced by significant increases in circulating platelet microaggregates and activated platelets. Thrombus was observed on 20 ± 6% of the surface area of devices implanted for up to 53 h. Adding aspirin to the antithrombotic therapy permitted two devices to remain implanted up to 96 h with reduced platelet activation and only 3% of the surface covered with thrombus. The application of heparin-based coatings significantly reduced thrombus deposition in vitro. The results suggest that with the use of appropriate antithrombotic therapies and surface coatings the Hattler Catheter might successfully provide support for acute lung failure without thrombotic complications. [ABSTRACT FROM AUTHOR]