Gas Exchange Membrane Research Articles

The new advanced membrane gas exchanger

Current membrane oxygenators are constructed for patients with a body surface under 2.2 m(2). If the body surface exceeds 2.5 m(2), commercially available devices may not allow adequate oxygenation during cardiopulmonary bypass. To address this, a hollow-fiber oxygenator with an enlarged contact surface of 1.81 m(2) was tested. In an experimental set-up, six calves of mean weight 85.4 ± 3 kg were connected to cardiopulmonary bypass. They were randomly assigned to a standard oxygenator (n = 3; ADMIRAL, Euroset, Medola, Italy) with a surface of 1.35 m(2) or to an enlarged surface oxygenator (n = 3; AMG, Euroset). Blood samples were taken before bypass, after 10 min on bypass, and after 1, 2, 5 and 6 h of perfusion. Analysis of variance was used for repeated measurements. The mean flow rate was 6.5 l/min for 6 h. The total oxygen transfer at 6 h was significantly higher in the high-surface group (P < 0.05). Blood trauma, evaluated by plasma hemoglobin and lactate dehydrogenase levels, did not detect any significant hemolysis. Thrombocytes and white blood cell count profiles showed no significant differences between the two groups at 6 h of perfusion (P = 0.06 and 0.80, respectively). At the end of testing, no clot deposition was found in the oxygenator, and there was no evidence of peripheral emboli. The results suggest that the new oxygenator allows very good gas transfer and may be used for patients with a large body surface area.

Addition of Acetylsalicylic Acid to Heparin for Anticoagulation Management During Pumpless Extracorporeal Lung Assist

Pump-driven extracorporeal membrane oxygenation (ECMO) or pumpless arterio-venous interventional lung assist (iLA) is associated with possible complications, mainly consisting of bleeding or thrombosis/clotting by cellular deposits on the membrane or extracorporeal circuit surfaces, which may reduce gas-exchange capacity. In this study, we report our experiences with the addition of low-dose acetylsalicylic acid (ASA 1.5 mg/kg body weight/d) to heparin for anticoagulation of a pumpless low-resistance gas-exchange membrane (Novalung GmbH, Talheim, Germany). We assessed changes in coagulation parameters and the demand for transfusion of blood components. Furthermore, we compared the function of the artificial membranes (oxygen transfer and capacity of CO2 removal) of the ASA group (n = 15) with that of a matched-pair control group treated with heparin alone. The mean duration of iLA treatment was 6.6 ± 3.7 days. The addition of ASA did not increase bleeding activity or the demand for transfusion. Relative changes of CO2 removal on day 3 expressed as a percentage in the ASA group were (mean value) -11.8% in comparison with control (-3.0%, p = 0.266), but the relative amount of oxygen transfer tended to be increased in the ASA group (+3.9%) and to be decreased in the control group (-14.7%, p = 0.214). PaO2/FiO2 ratio was significantly improved in the ASA group compared with the control group at day 5. The use of membranes per patient (membrane/patient ratio) tended to be decreased in patients treated with ASA (1.12 ± 0.34) in comparison with control (1.33 ± 0.62, p = 0.157). In the ASA group, one patient died due to multiple organ failure, whereas in the control group, five patients died. We conclude that supplementation of low-dose ASA during pumpless extracorporeal lung support is safe and might preserve the function of oxygen transfer.

Development of a biohybrid lung - unaffected gastransfer of Poly-4-Methyl-1-Pentene gasexchange membranes by endothelialisation

Objectives: The use of extracorporeal membrane oxygenators is limited by adverse reactions like the activation of the coagulation cascade leading to an insufficient gasexchange. Endothelialization is an important tool to optimize the blood compatibility of artificial materials Aiming towards the development of a bioartificial lung, the effect by endothelialisation of poly-4-methyl-1-pentene gasexchange membranes (PMP) respecting the gasexchange capability was evaluated.

A microfluidic respiratory assist device with high gas permeance for artificial lung applications

One of the principal challenges in artificial lung technology has been the ability to provide levels of oxygen and carbon dioxide exchange that rival those of the natural human lung, while mitigating the deleterious interaction between blood and the surface of the synthetic gas exchange membrane. This interaction is exacerbated by the large oxygenator surface area required to achieve sufficient levels of gas transfer. In an effort to address this challenge, microfluidics-based artificial lung technologies comprising stacked microchannel networks have been explored by several groups. Here we report the design, fabrication and initial testing of a parallel plate multilayered silicone-based microfluidic construct containing ultrathin gas exchange membranes, aimed at maximizing gas transfer efficiency while minimizing membrane-blood contact area. The device comprises a branched microvascular network that provides controlled wall shear stress and uniform blood flow, and is designed to minimize blood damage, thrombosis and inflammatory responses seen in current oxygenators. Initial testing indicates that flow distribution through the multilayer structure is uniform and that the thin membrane can withstand pressures equivalent to those expected during operation. Oxygen transfer using phosphate buffered saline as the carrier fluid has also been assessed, demonstrating a sharp increase in oxygen transfer as membrane thickness is reduced, consistent with the expected values of oxygen permeance for thin silicone membranes.

Reduced Thrombocyte Adhesion to Endothelialized Poly 4-Methyl-1-Pentene Gas Exchange Membranes—A First Step Toward Bioartificial Lung Development

Polymeric materials used in biomedical devices, bioartificial organs, or for the fabrication of tissue engineering scaffolds should completely prevent the activation of the coagulation system and subsequent clot formation. Surface endothelialization is considered an important tool to optimize the blood compatibility of synthetic materials, as a functional endothelial cell layer on an artificial material may help control hemostasis and, therefore, provide a solution to improve the biocompatibility of these materials. Here we report on the endothelialization of poly 4-methyl-1-pentene (PMP) gas exchange membranes using human cord blood-derived late outgrowth endothelial colony forming cells. We achieved complete endothelialization of PMP membranes; and when seeded and cultivated on the membrane, cord blood-derived late outgrowth endothelial colony forming cells maintained both endothelial characteristics and functionality. Endothelialization resulted in significantly lower platelet adhesion and activation compared with unseeded membranes. Of importance, the endothelial layer had no major impact on gas permeability of PMP membranes. This study is a first promising step toward the development of a biofunctionalized surface for the use in gas exchange devices with blood contacting surfaces and a straightforward approach toward a long-term bio-hybrid lung replacement system.

ECMO et SDRA : Canulation

Initially, extra corporeal membrane oxygenation (ECMO) was a respiratory assistance technique that used a membrane gas exchanger. By extension, ECMO is now a respiratory and cardiorespiratory assistance technique, used in case of respiratory and/or cardiac weakness. The hemodynamic support can be partial or total. ECMO is easily implanted thanks to peripheral vascular approaches. This kind of assistance uses the concept of “blood extracorporeal circulation”. The basic circuit is simple and includes a pump, an oxygenator (allowing CO 2 removal) and peripheral vascular approaches (one for drainage and one for reinjection). It is easy and fast to set up and can be done bedside. Despite recent technological progress, few centers use temporary respiratory assistance. However, some thoracic surgical units use ECMO in the framework of therapeutic interventions (lung transplantation in particular); in addition, some intensive care units use ECMO in the management and treatment of ARDS. In this chapter, we will first present the techniques of ECMO that can be used in the framework of ARDS, then we will describe the material, and finally we will study the area of implantation. In adult pulmonary pathologies, the key point is to develop the notion of “minimal strategy” with the use of an adjuvant partial extracorporeal circulation, allowing ad integrum recovering of patients. In the near future, technological improvement and a better knowledge of indications should improve the prognostic of patients under ECMO.

Branched vascular network architecture: A new approach to lung assist device technology

A lung assist device would serve an important clinical need as a bridge to transplant or destination therapy for patients with end-stage lung disease. A new lung assist device has been developed that incorporates a branched network of vascular channels adjacent to a gas chamber, separated by a thin, gas-permeable membrane. This study investigated 2 potential gas exchange membranes within this new architecture. Oxygen and carbon dioxide exchange within the device was tested in vitro using 3 gas-permeable membranes. Two of the membranes, silicone only and silicone-coated microporous polymer, were plasma impermeable. The third, a microporous polymer, was used as a control. Gas exchange testing was done using anticoagulated porcine blood over a range of flow rates. Oxygen and carbon dioxide transfer was demonstrated in the device and increased nearly linearly from 0.6 to 8.0 mL/min blood flow for all of the membranes. There was no significant difference in the gas transfer between the silicone and the silicone-coated microporous polymer membranes. The transfer of oxygen and carbon dioxide in the device was similar to existing hollow fiber oxygenators controlling for surface area. The silicone and silicone-coated microporous polymer membranes both show promise as gas-permeable membranes in a new lung assist device design. Further optimization of the device by improving the membranes and reducing the channel diameter in the vascular network will improve gas transfer. The current device may be scaled up to function as an adult lung assist device.

379: Improved Bloodcompatibility of a Poly-4-Methyl-1-Pentene Gas Exchange Membrane by Endothelialization

The use of artificial medical devices with blood contacting surfaces is inter alia limited by activation of the coagulation system. Aiming towards the engineering of a bioartificial lung, the improvement of the bloodcompatibility by a seeded endothelial monolayer onto a heparin/albumin coated gas exchange membrane (PMP) was investigated.

Improvement of bloodcompatibility of a poly-4-methyl-1-pentene gas exchange membrane by endothelialization

Objectives: The use of artificial medical devices with blood contacting surfaces is inter alia limited by activation of the coagulation system. Aiming towards the engineering of a bioartificial lung, the improvement of the bloodcompatibility by a seeded endothelial monolayer onto a heparin/albumin coated gas exchange membrane (PMP) was investigated.

Different Patterns of Physiological and Molecular Response to Drought in Seedlings of Malt‐ and Feed‐type Barleys (Hordeum vulgare)

AbstractA number of physiological and molecular characteristics are proposed as selection criteria for drought tolerance. This study measured the associations between physiological and molecular characteristics of drought response in malting and fodder spring barleys. Plants of 13 malt‐ and 14 feed‐type Polish genotypes were exposed to drought at the four‐leaf stage for 7 days. Drought susceptibility indexes (DSI) were calculated for membrane integrity, water status, gas exchange and PSII photochemical activity. Accumulation of HVA1 and SRG6 transcripts in drought was measured with real‐time PCR. A wide range of variation in the drought response was observed among studied genotypes. Malting barleys were less sensitive to drought than feed‐barleys according to all the traits studied. In both groups, different patterns of relationships between traits were observed. In malting genotypes only, CO2 assimilation rates in drought, as well as PSII efficiency were related to both water content and the accumulation of HVA1 transcript in leaves. On the other hand the SRG6 expression was highly correlated in both groups of barley with the photochemical efficiency of PSII. The results suggest that different physiological, biochemical and molecular characteristics should be applied in the selection towards drought resistance in the case of malting and fodder barleys.

Immersed superhydrophobic surfaces: Gas exchange, slip and drag reduction properties

Superhydrophobic surfaces combine high aspect ratio micro- or nano-topography and hydrophobic surface chemistry to create super water-repellent surfaces. Most studies consider their effect on droplets, which ball-up and roll-off. However, their properties are not restricted to modification of the behaviour of droplets, but potentially influence any process occurring at the solid-liquid interface. Here, we highlight three recent developments focused on the theme of immersed superhydrophobic surfaces. The first illustrates the ability of a superhydrophobic surface to act as a gas exchange membrane, the second demonstrates a reduction in drag during flow through small tubes and the third considers a macroscopic experiment demonstrating an increase in the terminal velocity of settling spheres.

Continuously infusing hyperpolarized 129Xe into flowing aqueous solutions using hydrophobic gas exchange membranes.

Hyperpolarized (HP) (129)Xe yields high signal intensities in nuclear magnetic resonance (NMR) and, through its large chemical shift range of approximately 300 ppm, provides detailed information about the local chemical environment. To exploit these properties in aqueous solutions and living tissues requires the development of methods for efficiently dissolving HP (129)Xe over an extended time period. To this end, we have used commercially available gas exchange modules to continuously infuse concentrated HP (129)Xe into flowing liquids, including rat whole blood, for periods as long as one hour and have demonstrated the feasibility of dissolved-phase MR imaging with submillimeter resolution within minutes. These modules, which exchange gases using hydrophobic microporous polymer membranes, are compatible with a variety of liquids and are suitable for infusing HP (129)Xe into the bloodstream in vivo. Additionally, we have developed a detailed mathematical model of the infused HP (129)Xe signal dynamics that should be useful in designing improved infusion systems that yield even higher dissolved HP (129)Xe signal intensities.

Role of hemoglobin oxygenation in the modulation of red blood cell mechanical properties by nitric oxide

It has been previously demonstrated that both externally generated and internally synthesized nitric oxide (NO) can affect red blood cell (RBC) deformability. Further studies have shown that the RBC has active NO synthesizing mechanisms and that these mechanisms may play role in maintaining normal RBC mechanical properties. However, hemoglobin within the RBC is known to be a potent scavenger of NO; oxy-hemoglobin scavenges NO faster than deoxy-hemoglobin via the dioxygenation reaction to nitrate. The present study aimed at investigating the role of hemoglobin oxygenation in the modulation of RBC rheologic behavior by NO. Human blood was obtained from healthy volunteers, anticoagulated with sodium heparin (15 IU/mL), and the hematocrit was adjusted to 0.4 L/L by adding or removing autologous plasma. Several two mL aliquots of blood were equilibrated at room temperature (22 ± 2 °C) with moisturized air or 100% nitrogen by a membrane gas exchanger, The NO donor sodium nitroprusside (SNP), at a concentration range of 10 −7–10 −4 M, was added to the equilibrated aliquots which were maintained under the same conditions for an additional 60 min. The effect of the non-specific NOS inhibitor l-NAME was also tested at a concentration of 10 −3 M. RBC deformability was measured using an ektacytometer with an environment corresponding to that used for the prior incubation (i.e., oxygenated or deoxygenated). Our results indicate an improvement of RBC deformability with the NO donor SNP that was much more pronounced in the deoxygenated aliquots. SNP also had a more pronounced effect on RBC aggregation for deoxygenated RBC. Conversely, l-NAME had no effect on deoxygenated blood but resulted in impaired deformability, with no change in aggregation for oxygenated blood. These findings can be explained by a differential behavior of hemoglobin under oxygenated and deoxygenated conditions; the influence of oxygen partial pressure on NOS activity may also play a role. It is therefore critical to consider the oxygenation state of intracellular hemoglobin while studying the role of NO as a regulator of RBC mechanical properties.

Comorbidities in heart failure: a key issue

Comorbidities in heart failure: a key issue

Extracorporeal circulatory systems in the interhospital transfer of critically ill patients: experience of a single institution

BACKGROUND AND OBJECTIVES:Critically ill patients with acute circulatory failure cannot be moved to other institutions unless stabilized by mechanical support systems. Extracorporeal heart and lung assist systems are increasingly used as a bridge to end-organ recovery or transplantation, and as an ultimate rescue tool in cardiopulmonary resuscitation.PATIENTS AND METHODS:From July 2001 to April 2008, we had 38 requests for extracorporeal support for interhospital transfer carried out by the air medical service. Respiratory failure was present in 29 patients, who were provided with pumpless extracorporeal lung assist (PECLA) or veno-venous extracorporeal membrane oxygenation (ECMO). Cardiac failure dominated in 9 patients, who underwent implantation of extracorporeal life support (ECLS). Underlying diseases were acute respiratory distress syndrome in 15 patients, pneumonia in 7, prior lung transplant status in 4, cardiogenic shock in 7, and septic shock in 4.RESULTS:All assist systems were connected via peripheral vessels by the Seldinger technique. Transport was uneventful in all cases with no technical failures. On arrival at the specialized care hospital, two patients had leg ischemia and underwent relocation of the arterial cannula. After a mean (SD) support of 5.1 (3.0) days for PECLA, 3.5 (2.9) days for ECLS, and 7.3 (5.8) days for ECMO, 60%, 66%, and 66% of patients, respectively, could be successfully weaned from the systems. Discharge rates were 45% for PECLA, 44% for ECLS, and 56% for ECMO.CONCLUSION:Our experience proves that minimized extracorporeal assist devices allow safe assistance of patients with isolated or combined heart and lung failure in need of interhospital transfer. Critically ill patients get a chance to reach a center of maximum medical care.

Extrakorporale Lungenunterstützungsverfahren (ECMO/iLA)

The management of acute lung injury in adults requires specific therapeutic measures including techniques of extracorporeal lung support. In patients suffering from severe acute respiratory distress syndrome (ARDS) with life-threatening hypoxaemia, a pump-driven, veno-venous extracorporeal membrane oxygenation (ECMO) has been established. Recently, a pumpless extracorporeal lung support system was developed using an arterio-venous bypass into which a gas exchange membrane is integrated ("interventional lung assist" [iLA]). ILA provides effective CO2 elimination and a moderate improvement in oxygenation. In both techniques, an improvement in survival has not been demonstrated in prospective investigations. ECMO and iLA might be associated with serious complications (bleeding, ischaemia), thus further randomised prospective studies are warranted to elucidate specific indications. In patients with severe asthma or exacerbation of chronic obstructive pulmonary disease, iLA might represent an attractive rescue therapy in the future.

Genotypic differences in leaf biochemical, physiological and growth responses to ozone in 20 winter wheat cultivars released over the past 60 years

AbstractOzone (O3) concentrations in periurban areas in East Asia are sufficiently high to decrease crop yield. However, little is known about the genotypic differences in O3 sensitivity in winter wheat in relation to year of cultivar release. This paper reports genotypic variations in O3 sensitivity in 20 winter wheat cultivars released over the past 60 years in China highlighting O3‐induced mechanisms. Wheat plants were exposed to elevated O3 (82 ppb O3, 7 h day−1) or charcoal‐filtered air (&lt;5 ppb O3) for 21 days in open top chambers. Responses to O3 were assessed by the levels of antioxidative activities, protein alteration, membrane lipid peroxidation, gas exchange, leaf chlorophyll, dark respiration and growth. We found that O3 significantly reduced foliar ascorbate (−14%) and soluble protein (−22%), but increased peroxidase activity (+46%) and malondialdehyde (+38%). Elevated O3 depressed light saturated net photosynthetic rate (−24%), stomatal conductance (−8%) and total chlorophyll (−11%), while stimulated dark respiration (+28%) and intercellular CO2 concentration (+39%). O3 also reduced overall plant growth, but to a greater extent in root (−32%) than in shoot (−17%) biomass. There was significant genotypic variation in potential sensitivity to O3 that did not correlate to observed O3 tolerance. Sensitivity to O3 in cultivars of winter wheat progressed with year of release and correlated with stomatal conductance and dark respiration in O3‐exposed plants. O3‐induced loss in photosynthetic rate was attributed primarily to impaired activity of mesophyll cells and loss of integrity of cellular membrane as evidenced by increased intercellular CO2 concentration and lipid peroxidation. Our findings demonstrated that higher sensitivity to O3 in the more recently released cultivars was induced by higher stomatal conductance, larger reduction in antioxidative capacity and lower levels of dark respiration leading to higher oxidative damage to proteins and integrity of cellular membranes.

From Baghdad to Germany: Use of a New Pumpless Extracorporeal Lung Assist System in Two Severely Injured US Soldiers

The authors describe a new extracorporeal pumpless interventional lung assist system (iLA) that was implemented in two US soldiers with severe acute respiratory distress syndrome received from enemy action in Iraq, who were at risk for critical hypoxemia/hypercapnia. The system is characterized by a new low-resistance gas exchange membrane that is integrated in an arterial-venous bypass established by cannulation of the femoral artery and vein. Cardiovascular stability is essential to produce sufficiently high blood flow rates over the gas exchange unit. After implantation of the interventional lung assist, oxygenation increased and carbon dioxide elimination improved rapidly. Ventilator settings were able to be adjusted to the decreased pulmonary gas exchange needs, making protective lung strategies possible. Air transport of both patients with the running iLA system was uneventful. The iLA was removed after 15 and 8 days of continuous operation, respectively, and both soldiers were successfully weaned from mechanical ventilation. Interventional, extracorporeal pump-free pulmonary support opens up new possibilities for pulmonary protection due to ease of use, effectiveness, and low costs; however, there is concern of distal limb ischemia. Experiences to date are encouraging, although randomized studies are lacking, and the procedure carries significant risks.

Clinical experience with the iLA Membrane Ventilator pumpless extracorporeal lung-assist device

Extracorporeal gas exchange by extracorporeal membrane oxygenation has been established clinically in patients with acute lung failure. The interventional lung-assist (iLA) Membrane Ventilator device (Novalung®) is a sophisticated representative of a new generation of pumpless extracorporeal lung-assist devices that are driven by the patient’s cardiac output and therefore, do not require extracorporeal pump assistance. The system is characterized by a new membrane gas exchange system with optimized blood flow that is integrated in an arteriovenous bypass established by vascular cannulation. This particular pumpless extracorporeal lung-assist device was applied in 1800 patients for artificial lung assistance with easy use and low cost. This article reviews the present state of clinical Novalung device implementation focusing on encountered limitations and conceivable future developments in the field.

Feasibility Study of Using Brine for Carbon Dioxide Capture and Storage from Fixed Sources

A laboratory-scale reactor was developed to evaluate the capture of carbon dioxide (CO2) from a gas into a liquid as an approach to control greenhouse gases emitted from fixed sources. CO2 at 5–50% concentrations was passed through a gas-exchange membrane and transferred into liquid media—tap water or simulated brine. When using water, capture efficiencies exceeded 50% and could be enhanced by adding base (e.g., sodium hydroxide) or the combination of base and carbonic anhydrase, a catalyst that speeds the conversion of CO2 to carbonic acid. The transferred CO2 formed ions, such as bicarbonate or carbonate, depending on the amount of base present. Adding precipitating cations, like Ca++, produced insoluble carbonate salts. Simulated brine proved nearly as efficient as water in absorbing CO2, with less than a 6% reduction in CO2 transferred. The CO2 either dissolved into the brine or formed a mixture of gas and ions. If the chemistry was favorable, carbonate precipitate spontaneously formed. Energy expenditure of pumping brine up and down from subterranean depths was modeled. We conclude that using brine in a gas-exchange membrane system for capturing CO2 from a gas stream to liquid is technically feasible and can be accomplished at a reasonable expenditure of energy.