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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.

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 Auto-Regulatory 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 (SpO(2) = 96.3 % ± 4.29, pH = 7.44 ± 0.09, pCO(2) = 38.9 ± 9.9 mmHg, and pO(2) =237.9 ± 123.6 mmHg) during simulated respiratory distress. Acceptable correlation between oxygenator exhaust gas CO(2) and oxygenator outlet pCO(2) were observed (R(2)= 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.

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.

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.

Extracorporeal membrane oxygenation (ECMO) is a life support system that circulates the blood through an oxygenating system to temporarily (days to months) support heart or lung function during cardiopulmonary failure until organ recovery or replacement. Currently, the need for high levels of systemic anticoagulation and the risk for bleeding are main drawbacks of ECMO that can be addressed with a redesigned ECMO system. Our lab has developed an approach using microelectromechanical systems (MEMS) fabrication techniques to create novel gas exchange membranes consisting of a rigid silicon micropore membrane (SμM) support structure bonded to a thin film of gas-permeable polydimethylsiloxane (PDMS). This study details the fabrication process to create silicon membranes with highly uniform micropores that have a high level of pattern fidelity. The oxygen transport across these membranes was tested in a simple water-based bench-top set-up as well in a porcine in vivo model. It was determined that the mass transfer coefficient for the system using SµM-PDMS membranes was 3.03 ± 0.42 mL O2 min−1 m−2 cm Hg−1 with pure water and 1.71 ± 1.03 mL O2 min−1 m−2 cm Hg−1 with blood. An analytic model to predict gas transport was developed using data from the bench-top experiments and validated with in vivo testing. This was a proof of concept study showing adequate oxygen transport across a parallel plate SµM-PDMS membrane when used as a membrane oxygenator. This work establishes the tools and the equipoise to develop future generations of silicon micropore membrane oxygenators.

Flow distribution is key in artificial lungs, as it directly influences gas exchange performance as well as clot forming and blood damaging potential. The current state of computational fluid dynamics (CFD) in artificial lungs can only give insight on a macroscopic level due to model simplification applied to the fiber bundle. Based on our recent work on wound fiber bundles, we applied particle image velocimetry (PIV) to the model of an artificial lung prototype intended for neonatal use to visualize flow distribution in a stacked fiber bundle configuration to (i) evaluate the feasibility of PIV for artificial lungs, (ii) validate CFD in the fiber bundle of artificial lungs, and (iii) give a suggestion how to incorporate microscopic aspects into mainly macroscopic CFD studies. To this end, we built a fully transparent model of an artificial lung prototype. To increase spatial resolution, we scaled up the model by a factor of 5.8 compared with the original size. Similitude theory was applied to ensure comparability of the flow distribution between the device of original size and the scaled-up model. We focused our flow investigation on an area (20 × 70 × 43 mm) in a corner of the model with a Stereo-PIV setup. PIV data was compared to CFD data of the original sized artificial lung. From experimental PIV data, we were able to show local flow acceleration and declaration in the fiber bundle and meandering flow around individual fibers, which is not possible using state-of-the-art macroscopic CFD simulations. Our findings are applicable to clinically used artificial lungs with a similar stacked fiber arrangement (e.g., Novalung iLa and Maquet QUADROX-I). With respect to some limitations, we found PIV to be a feasible experimental flow visualization technique to investigate blood-sided flow in the stacked fiber arrangement of artificial lungs.

Stability and antithrombotic functionality of endothelial cells on silicone hollow fibers (SiHFs) are critical in the development of biohybrid artificial lungs. Here we aimed to enhance endothelial cell retention and anti-thrombotic function by low (12 dyn/cm2 , 24 h) fluid shear stress ("flow") preconditioning of endothelial cells seeded on collagen-immobilized SiHFs. The response of endothelial cells without preconditioning (48 h static culture) and with preconditioning (24 h static culture followed by 24 h flow preconditioning) on hollow fibers to high fluid shear stress (30 dyn/cm2 , 1 h) was assessed in a parallel-plate flow chamber. Finite element (FE) modeling was used to simulate shear stress within the flow chamber. We found that collagen immobilization on hollow fibers using carbodiimide bonds provided sufficient stability to high shear stress. Flow preconditioning for 24 h before treatment with high shear stress for 1 h on collagen-immobilized hollow fibers increased cell retention (1.3-fold). The FE model showed that cell flattening due to flow preconditioning reduced maximum shear stress on cells by 32%. Flow preconditioning prior to exposure to high fluid shear stress enhanced the production of nitric oxide (1.3-fold) and prostaglandin I2 (1.2-fold). In conclusion, flow preconditioning of endothelial cells on collagen-immobilized SiHFs enhanced cell retention and antithrombotic function, which could significantly improve current biohybrid artificial lungs.

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.

Providing partial respiratory assistance by removing carbon dioxide (CO2 ) can improve clinical outcomes in patients suffering from acute exacerbations of chronic obstructive pulmonary disease and acute respiratory distress syndrome. An intravenous respiratory assist device with a small (25 Fr) insertion diameter eliminates the complexity and potential complications associated with external blood circuitry and can be inserted by nonspecialized surgeons. The impeller percutaneous respiratory assist catheter (IPRAC) is a highly efficient CO2 removal device for percutaneous insertion to the vena cava via the right jugular or right femoral vein that utilizes an array of impellers rotating within a hollow-fiber membrane bundle to enhance gas exchange. The objective of this study was to evaluate the effects of new impeller designs and impeller spacing on gas exchange in the IPRAC using computational fluid dynamics (CFD) and in vitro deionized water gas exchange testing. A CFD gas exchange and flow model was developed to guide a progressive impeller design process. Six impeller blade geometries were designed and tested in vitro in an IPRAC device with 2- or 10-mm axial spacing and varying numbers of blades (2-5). The maximum CO2 removal efficiency (exchange per unit surface area) achieved was 573 ± 8 mL/min/m(2) (40.1 mL/min absolute). The gas exchange rate was found to be largely independent of blade design and number of blades for the impellers tested but increased significantly (5-10%) with reduced axial spacing allowing for additional shaft impellers (23 vs. 14). CFD gas exchange predictions were within 2-13% of experimental values and accurately predicted the relative improvement with impellers at 2- versus 10-mm axial spacing. The ability of CFD simulation to accurately forecast the effects of influential design parameters suggests it can be used to identify impeller traits that profoundly affect facilitated gas exchange.

Summary Objective There is little available data on airway humidity during high-frequency ventilation (HFV). The purpose of this study is to evaluate the temperature drop in an endotracheal tube (ETT) during HFV. Methods We examined the airway temperature in a neonatal HFV system using Babylog® 8000 plus. We measured the temperature change of inspired gases in the ETT under various oscillatory frequencies and oscillatory volumes with a fixed base flow. The temperatures in the ETT during HFV were compared with the temperatures during conventional intermittent positive pressure ventilation (IPPV). Results As the oscillatory frequency was increased and the oscillatory volume (VThf) decreased, the difference in temperature between the Y piece and the inlet of an artificial lung in the ETT (ETT outside of body) increased. However, as the oscillatory frequency increased, there was no difference in the ETT temperature under constant oscillatory volume. In contrast, as the oscillatory volume was decreased, the difference in temperature in the ETT was greater under constant oscillatory frequency. Moreover, the temperature drop in the ETT with HFV was lower than that in the IPPV temperature with a similar respiratory volume. Conclusions The temperature change in the ETT was not dependent on the oscillatory frequency when the oscillatory volume was fixed; however, the temperature was dependent on the oscillatory volume when the oscillatory frequency was fixed. Pediatr Pulmonol. 2015; 50:173–178. © 2013 Wiley Periodicals, Inc.

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 hrs at an activated clotting time of 350-400s. 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 hours (15.38 ± 9.65, p

The purpose of this study was to assess the biocompatibility of a newly developed long-term wearable artificial pump-lung (APL) in a clinically relevant ovine animal model. The wearable APL device was implanted in five sheep through left thoracotomy. The device was connected between the right atrium and pulmonary artery and evaluated for 30 days. Three sheep were used as the sham control. Platelet activation was assessed by measuring platelet surface P-selectin (CD62P) expression with flow cytometry and plasma soluble P-selectin with an enzyme-linked immunosorbent assay. Thrombotic deposition on the device components and hollow fiber membranes were analyzed with digital imaging and scanning electron microscopy. Surface P-selectin of the APL and sham groups changed significantly over the study period, but without significant differences between the two groups. Soluble P-selectin for the two groups peaked in the first 24 h after the surgery. Soluble P-selectin of the APL group remained slightly elevated over the study period compared to the presurgical baseline value and was slightly higher compared to that of the sham group. Plasma free hemoglobin remained in the normal ranges in all the animals. In spite of the surgery-related alteration in laboratory tests and elevation of platelet activation status, the APL devices in all the animals functioned normally (oxygen transfer and blood pumping) during the 30-day study period. The device flow path and membrane surface were free of gross thrombus. Electron microscopy images showed only scattered thrombi on the fibers (membrane surface and weft). In summary, the APL exhibited excellent biocompatibility. Two forms of platelet activation, surgery-related and device-induced, in the animals implanted with the wearable APL were observed. The limited device-induced platelet activation did not cause gross thrombosis and impair the long-term device performance.

Mechanical ventilation and extracorporeal membrane oxygenation are the only immediate options available for patients with respiratory failure. However, these options present significant shortcomings. To address this unmet need for respiratory support, innovative respiratory assist devices are being developed. In this study, we present the computational model-based design, and analysis of functional characteristics and hemocompatibility performance, of an innovative wearable artificial pump-lung (APL) for ambulatory respiratory support. Computer-aided design and computational fluid dynamics (CFD)-based modeling were utilized to generate the geometrical model and to acquire the fluid flow field, gas transfer, and blood damage potential. With the knowledge of flow field, gas transfer, and blood damage potential through the whole device, design parameters were adjusted to achieve the desired specifications based on the concept of virtual prototyping using the computational modeling in conjunction with consideration of the constraints on fabrication processes and materials. Based on the results of the CFD design and analysis, the physical model of the wearable APL was fabricated. Computationally predicted hydrodynamic pumping function, gas transfer, and blood damage potential were compared with experimental data from in vitro evaluation of the wearable APL. The hydrodynamic performance, oxygen transfer, and blood damage potential predicted with computational modeling, along with the in vitro experimental data, indicated that this APL meets the design specifications for respiratory support with excellent biocompatibility at the targeted operating condition.

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 48mL/min/L(blood) at a medium blood flow rate of about 300mL/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.

In this work an automatic control strategy is presented for the simultaneous control of oxygen and carbon dioxide blood gas partial pressures to be used during cardiopulmonary bypass surgery with heart-lung machine support. As the exchange of blood gases in the artificial extracorporeal lung is a highly nonlinear process comprising varying time delays, uncertainties, and time-varying parameters, it is currently being controlled manually by specially trained perfusionist staff. The new control strategy includes a feedback linearization routine with augmented time-delay compensation and two external linear gain-scheduled controllers, for partial oxygen and carbon dioxide pressures. The controllers were robustly tuned and tested in simulations with a detailed artificial lung (oxygenator) model in cardiopulmonary bypass conditions. Furthermore, the controllers were implemented in an ex vivo experiment using fresh porcine blood as a substitute fluid and a special deoxygenation technique to simulate a patient undergoing cardiopulmonary bypass. Both controllers showed robust stability during the experiments and a good disturbance rejection to extracorporeal blood flow changes. This automatic control strategy is proposed to improve patient's safety by fast control reference tracking and good disturbance rejection under varying conditions.

Artificial lungs composed of bundles of micro-porous hollow fiber membranes (HFMs), which are made from polymeric materials such as poly (methylpentene) and poly(propylene), are routinely employed to both oxygenate blood and remove carbon dioxide (CO2) in an extraluminal blood flow format. The efficiency of CO2 and oxygen (O2) gas exchange in the current artificial lung model, which is based on passive diffusion, is limited by the fiber surface area to blood volume ratio with devices requiring approximately 1–2 m2 of HFM surface to provide adequate gas exchange (1,2). Such large blood-contacting surfaces present significant challenges to hemocompatibility, necessitating aggressive anticoagulation and stimulating research into devices with improved efficiency (i.e., smaller) and hemocompatibility. A wide variety of surface modification techniques have been evaluated to reduce the thrombogenicity of blood-contacting biomaterials, although there have been relatively few reports specifically focused on the HFMs utilized in artificial lung applications. Siloxane-grafted HFMs prepared by a plasma polymerization process with 1,3,3,7-tetramethyhydrocyclosiloxane (TMCTS)-coated fibers have shown reduced thrombogenesis relative to unmodified fibers (3). Plasma polymerization techniques have a number of advantages with regard to surface modification including: facile preparation of a thin, conformal, and pinhole-free coating; amenability to a wide variety of substrates; achievement of good adhesion between coating and substrate; and the ability to generate coatings that present excellent thermal and chemical resistance (4,5). Another approach to improving artificial lung biocompatibility is to effectively reduce the required HFM surface area by increasing the gas exchange rate of HFM-based devices. Increasing the efficiency of CO2 removal is especially important because the natural concentration gradient for CO2 diffusion is much smaller than that for O2 addition. Furthermore, in many patients with respiratory failure, the need for CO2 removal is more important clinically, as oxygenation can be provided by nasal cannula or lung-protective ventilation (1,6–8). In a previous study, we reported the development of a bioactive HFM that could improve CO2 removal rates in lung failure patients (9). Carbonic anhydrase (CA) was covalently immobilized to the surface of a conventional HFM, and by catalyzing the dehydration of bicarbonate in blood was shown to facilitate diffusion of CO2 toward the fiber membranes, essentially mimicking the function of the enzyme on lung capillary surfaces. Results indicated that CO2 exchange rates from buffer were increased by as much as 75% in the model device. In this brief report, we addressed whether the attachment of CA onto a HFM surface increased fiber thrombogenicity, which would negate the biocompatibility benefits associated with a smaller device. A commercial poly(propylene) HFM (Celgard, Charlotte, NC,USA) was used as the base material and for control purposes. Fibers representing the intermediate modification steps of siloxane coating and amine grafting on siloxane (Alung Technologies, Pittsburgh, PA, USA) as well as the final CA-modified fiber were evaluated. A second control of a commercial poly (methyl pentene) HFM (Oxyplus, Membrana, Wuppertal, Germany) was also included.

We report on the experimental application of nafamostat mesilate (NM, 6-amidino-2-naphthyl p-guanidinobenzoate dimethanesulfonate, FUT), a new anticoagulant, to extracorporeal lung assist (ECLA) with an artificial membrane lung. Venovenous ECLA, from the jugular vein to the femoral vein, was performed with a hollow-fiber membrane lung at a blood flow rate of approximate 82 ml kg-1 min-1 for 24 h in 7 dogs under anesthesia and hypoventilation. Heparin (10 U ml-1 in a priming lactated Ringer solution of 140 ml, and 200 U kg-1) was administered before blood access cannulation. After start of ECLA, however, no heparin was used, and nafamostat mesilate was continuously infused into the drainage line of the bypass circuit to control activated coagulation time (ACT) at about 150 to 200 s. To maintain the prolonged ACT, 8.0 +/- 1.7 mg kg-1 h-1 of NM was required. Arterial blood pressure and pulse rate decreased significantly. Though fibrin monomer test revealed hypercoagulability after 6 h of ECLA, platelet counts did not significantly decrease. Total blood loss remained less than 40 g. The artificial membrane lung sustained a good gas exchange and low flow resistance throughout ECLA. Macroscopic examination revealed small spotty thrombi in the artificial lung but no major pathologic changes of the visceral organs in the all dogs at autopsy. High-dose NM administration could control blood coagulation and decrease blood loss during ECLA for 24 h without deterioration of the artificial lung and systemic complication other than mild hypotension and bradycardia.

Using an airway mannequin and artificial lung model, we compared surgical cricothyroidotomy with a 6.0-mm cuffed Portex tracheostomy tube with wire-guided cricothyroidotomy using a 5.0-mm cuffed Melker or 6.0-mm uncuffed Melker tube. The trial was carried out by 27 anaesthetists using a randomised, crossover design. Surgical cricothyroidotomy proved significantly faster (mean (SD) time to first breath 44.3 (12.5) s for Portex surgical, 87.2 (21.6) s for cuffed Melker, 87.8 (19.2) s for uncuffed Melker, p < 0.001). With a standardised ventilator model, the cuffed tubes provided more effective ventilation (mean (SD) tidal volume 446 (41) ml Portex, 436 (52) ml cuffed Melker, 19 (5) ml uncuffed Melker, p < 0.001). Fourteen of the participants preferred the wire-guided system. We conclude that, in this model, a cuffed device is preferable when cricothyroidotomy is needed. In addition, the surgical method is quicker than a wire-guided approach.

Thrombosis and bleeding are major complications in cases of prolonged extracorporeal lung assist (ECLA) with an artificial-membrane lung. Antithrombogenic treatment of the artificial-membrane oxygenator and circuits is indispensable for safe ECLA. The efficacy of a new heparin-coated membrane lung with minimal systemic heparinization was evaluated for 7 days and compared with a nonheparin-coated membrane lung in goats. The animals were randomly assigned to either the heparin-coated membrane group (HM group, n = 5) or nonheparin-coated membrane group (NHM group, n = 5). Activated coagulation time (ACT) during ECLA was controlled to below 150 s in the HM group, and to near 200 s in the NHM group. All goats in the HM group were sustained on ECLA for 7 days, but two goats in the NHM group died on the 4th and 6th days, respectively. The mean systemic administration rate of heparin during ECLA was 22.4 +/- 4.4 U/kg/h in the HM group and 39.0 +/- 10.0 U/kg/h in the NHM group. There was a significant difference between the two groups (P < 0.05). The oxygen transfer rate, the Pco(2) difference, the perfusion resistance, and platelet counts showed no significant changes. There was no plasma leakage from the artificial lung. Although several clots were observed in the stagnant areas of the artificial lung, they did not lead to deterioration of the function of the artificial lung. The excellent antithrombogenicity, gas exchange ability, and durability of this new artificial lung with circuits might contribute to successful prolonged ECLA with minimal systemic heparinization.

Background: Massive alveolar lavage has been used clinically to remove materials accumulated in the alveoli. Recently, filling the lungs with oxygenated perfluorochemical (total liquid ventilation) has been investigated. However, effects of complete and prolonged filling of bilateral lungs with aqueous fluid, such as saline or Ringer’s solution, has not been evaluated, although it is possible to sustain gas exchange without the natural lung by using extracorporeal circulation and an artificial lung (extracorporeal lung assist: ECLA). It is also not known whether the lung can recover gas exchange ability after prolonged fluid filling. Methods: Normal mongrel dogs were endotracheally intubated under general anesthesia and mechanically ventilated. After initiation of venoarterial ECLA, warmed lactated Ringer’s solution was instilled into the lungs through the endotracheal tube, and the lungs were completely filled at a hydrostatic pressure of 15 cmH2O (fluid-filled group: group F). After the lungs were filled for 4 h, the fluid was drained and ventilation was re-instituted. ECLA, then mechanical ventilation was gradually weaned within 24 h after fluid drainage. In control group (group C), dogs were kept apneic for 4 h with their lungs inflated at an airway pressure of 15 cmH2O with air. Results: Transient hypoxemia occurred during fluid filling but every dog could be weaned from ECLA and mechanical ventilation to spontaneous respiration. The average rate of fluid absorption from the lung during fluid filling was 4.2±1.8 ml kg−1 h−1. After fluid drainage and restart of mechanical ventilation, bilateral lungs were expanded and well aerated. Total static respiratory system compliance (static compliance) remained unchanged even after fluid filling, and the weight of the lung water did not increase significantly compared to that in group C. Total urine volume was significantly increased in group F. Histologically, alveolar structures were preserved and no interstitial edema or bleeding was seen in either group. Conclusion: Complete filling of the bilateral lungs for 4 h with lactated Ringer’s solution under ECLA causes no deterioration in gas exchange or static compliance in normal dogs, although transient hypoxemia occurs during fluid filling.

The gas transfer performances in a gas/membrane/liquid system were investigated in detail with various membranes. It was found that the oxygen flux in the gas/membrane/liquid system was saturated when the oxygen flux (Fg-g) in the gas/membrane/gas system became more than 1.0 x 10(-5) cm3 (STP) cm-2s-1cm Hg-1 (Fcg-g). This was explained as follows: The resistance of a boundary layer at liquid phase is dominant, i.e., the membrane resistance is negligible in the region of Fg-g which is greater than Fcg-g. Consequently, Fg-g of the membrane should be designed to be greater than Fcg-g, in order to satisfy the gas transfer performance required for blood oxygenation. On the basis of the results above, we have developed a new three-layered composite hollow fiber membrane (MHF) consisting of an ultrathin polyurethane layer supported between two microporous polyethylene layers to prevent serum leakage. It was shown through the evaluation in vitro that MHF had good gas transfer performances for long-term perfusion, and no serum leakage was observed. These characteristics suggest that MHF is quite suitable for long-term usage such as extracorporeal membrane oxygenation (ECMO).

A simple analysis and graphic result are presented for characterizing the dependence of CO2 exchange on the sweep gas (ventilating gas) flowrate in artificial lungs. The analysis requires no knowledge of the device-specific mass transfer characteristics of an artificial lung, nor does it require detailed mathematical modeling or computer simulation. Rather, it uses appropriate normalization to establish generic features of the gas flow dependency of CO2 exchange that are applicable to all artificial lung devices. Principal results are that the transition from relatively gas flow-sensitive to gas flow-insensitive CO2 exchange occurs at sweep gas flowrates of approximately 40-60 times the CO2 exchange rate. Achieving a CO2 exchange rate within 85% of maximal (for a given oxygenator and blood-side conditions) requires a sweep gas flowrate of no less than approximately 50 times the nominal CO2 exchange rate. When the sweep gas flowrate is less than 20 times the CO2 exchange rate, CO2 exchange is highly gas flow dependent and less than one-half the maximal possible rate.

Purpose: To develop a reproducible, tissue equivalent, deformable lung phantom for verification of 4D‐CT scanning procedures, deformable image registration (DIR) and 4D dose calculation in moving/deformable anatomies.Methods and Materials: The phantom consists of a Lucite cylinder filled with water containing a latex balloon filled with dampened natural sponges. The balloon is attached to a piston that mimics the human diaphragm. Nylon wires and Lucite beads, emulating vascular and bronchial bifurcations, were glued at various locations, uniformly, throughout the sponges. The phantom is capable of simulating programmed irregular breathing patterns with varying periods and amplitudes. A deformable, tissue equivalent tumour holding radiochromic film was embedded in the sponge. Eight 3D‐CT datasets (0.7×0.7×1.25 mm) of the phantom in eight static positions of the piston were acquired. 3D trajectories of 12 anatomical point landmarks as well as the tumour center‐of‐mass were studied. Results: Reproducible lung deformation is achieved by piston‐provoked pressure changes in water surrounding the deforming balloon. The resulting mean density for the artificial lung was 0.243 g/cm3 comparable to 0.252 g/cm3 for a real lung. A truly 3D, non‐isotropic deformation of the balloon similar to a real lung has been obtained. The SI displacement of the landmarks varies between 94% and 3% of the diaphragm excursion for positions closer and farther away from the diaphragm, respectively. Reproducibility in the deformed phantom, established by seven repeat scans at the same phantom compression state, was within image resolution. The accuracy of DIR of the extreme phases was 0.7(±0.7) mm. Conclusions: Our novel phantom is tissue‐equivalent, deformable, and can reproducibly emulate 3D non‐isotropic lung deformations. The presence of vascular and bronchial bifurcations allows verification of DIR of 4D‐CT images of the phantom. Registered phases of the phantom can be used in 4D dose calculations that can be validated by comparison with dose measurements.