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Oxidative Medicine and Cellular... 2018Most mammalian tissue cells experience oxygen partial pressures equivalent to 1-6% O (i.e., physioxia). In standard cell culture, however, headspace O levels are... (Review)
Review
Most mammalian tissue cells experience oxygen partial pressures equivalent to 1-6% O (i.e., physioxia). In standard cell culture, however, headspace O levels are usually not actively regulated and under these conditions are ~18%. This drives hyperoxia in cell culture media that can affect a wide variety of cellular activities and may compromise the ability of models to reproduce biology. Here, we review and discuss some specific O-consuming organelles and enzymes, including mitochondria, NADPH oxidases, the transplasma membrane redox system, nitric oxide synthases, xanthine oxidase, and monoamine oxidase with respect to their sensitivities to O levels. Many of these produce reactive oxygen and/or nitrogen species (ROS/RNS) as either primary end products or byproducts and are acutely sensitive to O levels in the range from 1% to 18%. Interestingly, many of them are also transcriptional targets of hypoxia-inducible factors (HIFs) and chronic cell growth at physioxia versus 18% O may alter their expression. Aquaporins, which facilitate hydrogen peroxide diffusion into and out of cells, are also regulated by HIFs, indicating that O levels may affect intercellular communication via hydrogen peroxide. The O sensitivities of these important activities emphasize the importance of maintaining physioxia in culture.
Topics: Animals; Cell Culture Techniques; Cell Respiration; Humans; Mitochondria; Oxygen; Oxygen Consumption; Reactive Oxygen Species
PubMed: 30363917
DOI: 10.1155/2018/8238459 -
Artificial Organs Mar 2021Extreme prematurity, defined as a gestational age of fewer than 28 weeks, is a significant health problem worldwide. It carries a high burden of mortality and... (Review)
Review
Extreme prematurity, defined as a gestational age of fewer than 28 weeks, is a significant health problem worldwide. It carries a high burden of mortality and morbidity, in large part due to the immaturity of the lungs at this stage of development. The standard of care for these patients includes support with mechanical ventilation, which exacerbates lung pathology. Extracorporeal life support (ECLS), also called artificial placenta technology when applied to extremely preterm (EPT) infants, offers an intriguing solution. ECLS involves providing gas exchange via an extracorporeal device, thereby doing the work of the lungs and allowing them to develop without being subjected to injurious mechanical ventilation. While ECLS has been successfully used in respiratory failure in full-term neonates, children, and adults, it has not been applied effectively to the EPT patient population. In this review, we discuss the unique aspects of EPT infants and the challenges of applying ECLS to these patients. In addition, we review recent progress in artificial placenta technology development. We then offer analysis on design considerations for successful engineering of a membrane oxygenator for an artificial placenta circuit. Finally, we examine next-generation oxygenators that might advance the development of artificial placenta devices.
Topics: Artificial Organs; Equipment Design; Extracorporeal Membrane Oxygenation; Female; Humans; Infant, Extremely Premature; Oxygenators, Membrane; Placenta; Pregnancy
PubMed: 32979857
DOI: 10.1111/aor.13827 -
Perfusion May 2023The novel Capiox NX19 adult oxygenator is, compared to its predecessors, improved with enhanced air removal technology, a polymer heat exchanger and smaller, innovative...
INTRODUCTION
The novel Capiox NX19 adult oxygenator is, compared to its predecessors, improved with enhanced air removal technology, a polymer heat exchanger and smaller, innovative hollow fibers resulting in a surface area reduction and a lower priming volume. The aim of this study was to evaluate the NX19 oxygenator performance in a clinical setting.
METHODS
A prospective multicenter study was performed involving three large European university hospitals. The Capiox NX19 ( = 150) performance was assessed during adult cardiopulmonary bypass and involved gaseous microemboli handling and gas transfer efficiency. The heat exchanger performance was evaluated separately in vitro.
RESULTS
The heat exchanger performance factors were 0.80 ± 0.03 and 0.58 ± 0.04 at pump flow rates of 3 L/min and 6 L/min, respectively. After priming, residual post-oxygenator gaseous microemboli count and volume were decreased by 91% and 93.7%, respectively. The gas compartment pressure was 6.0 ± 2.5 mmHg, while the O transfer was 69 ± 30 mL/min/m and the CO transfer 73 ± 34 mL/min/m. The O gradient was 44 ± 19 mmHg/LPM and the O diffusing capacity 0.38 ± 0.14 mL/min/mmHg. The shunt fraction was 0.19 ± 0.13, whereas oxygenator resistance and shear stress were 10.5 ± 3.7 mmHg/LPM and 5.1 ± 3.1 dyn/cm, respectively.
CONCLUSION
This multicenter study displayed good clinical safety and performance of the NX19 oxygenator.
Topics: Adult; Humans; Oxygenators, Membrane; Prospective Studies; Equipment Design; Extracorporeal Membrane Oxygenation; Cardiopulmonary Bypass; Gases
PubMed: 35348392
DOI: 10.1177/02676591221078942 -
Cellular and Molecular Life Sciences :... Jun 2012In recent years, significant progress has been achieved in the sensing and imaging of molecular oxygen (O(2)) in biological samples containing live cells and tissue. We... (Review)
Review
In recent years, significant progress has been achieved in the sensing and imaging of molecular oxygen (O(2)) in biological samples containing live cells and tissue. We review recent developments in the measurement of O(2) in such samples by optical means, particularly using the phosphorescence quenching technique. The main types of soluble O(2) sensors are assessed, including small molecule, supramolecular and particle-based structures used as extracellular or intracellular probes in conjunction with different detection modalities and measurement formats. For the different O(2) sensing systems, particular attention is paid to their merits and limitations, analytical performance, general convenience and applicability in specific biological applications. The latter include measurement of O(2) consumption rate, sample oxygenation, sensing of intracellular O(2), metabolic assessment of cells, and O(2) imaging of tissue, vasculature and individual cells. Altogether, this gives the potential user a comprehensive guide for the proper selection of the appropriate optical probe(s) and detection platform to suit their particular biological applications and measurement requirements.
Topics: Animals; Cell Respiration; Luminescent Measurements; Mice; Optical Devices; Oxygen; Rats
PubMed: 22249195
DOI: 10.1007/s00018-011-0914-0 -
International Journal of Molecular... Oct 2018Otto Warburg, a Nobel prize winner, observed that cancer cells typically "switch" from aerobic to anaerobic respiration. He hypothesized that mitochondrial damage... (Review)
Review
Otto Warburg, a Nobel prize winner, observed that cancer cells typically "switch" from aerobic to anaerobic respiration. He hypothesized that mitochondrial damage induces neoplastic transformation. In contrast, pathological aging is observed mainly in neuron cells in neurodegenerative diseases. Oxidative respiration is particularly active in neurons. There is inverse comorbidity between cancer and neurodegenerative diseases. This led to the creation of the "inverse Warburg hypothesis", according to which excessive mitochondrial activity induces pathological aging. The findings of our studies suggest that both the Warburg effect and the "inverse Warburg hypothesis" can be elucidated by the activation or suppression of apoptosis through oxidative respiration. The key outcome of our phylogenetic studies was the discovery that apoptosis and apoptosis-like cell death evolved due to an evolutionary "arms race" conducted between "prey" protomitochondrion and "predator" primitive eukaryotes. The ancestral protomitochondrial machinery produces and releases toxic mitochondrial proteins. Extant apoptotic factors evolved from these toxins. Our experiments indicate that the mitochondrial machinery is directly involved in adaptation to aerobic conditions. Additionally, our hypothesis is supported by the fact that different apoptotic factors are directly involved in respiration.
Topics: Aging; Animals; Apoptosis; Cell Respiration; Cell Transformation, Neoplastic; Energy Metabolism; Eukaryota; Humans; Mitochondria; Neoplasms; Neurodegenerative Diseases; Oxygen; Symbiosis
PubMed: 30308966
DOI: 10.3390/ijms19103100 -
ASAIO Journal (American Society For... Jul 2023Membrane oxygenator failure during venovenous (V-V) extracorporeal membrane oxygenation (ECMO) can lead to life-threatening hypoxia, high replacement costs, and may be...
Membrane oxygenator failure during venovenous (V-V) extracorporeal membrane oxygenation (ECMO) can lead to life-threatening hypoxia, high replacement costs, and may be associated with a hyperfibrinolytic state and bleeding. The current understanding of the underlying mechanisms that drive this is limited. The primary aim of this study therefore is to investigate the hematological changes that occur before and after membrane oxygenator and circuit exchanges (ECMO circuit exchange) in patients with severe respiratory failure managed on V-V ECMO. We analyzed 100 consecutive V-V ECMO patients using linear mixed-effects modeling to evaluate hematological markers in the 72 hours before and 72 hours after ECMO circuit exchange. A total of 44 ECMO circuit exchanges occurred in 31 of 100 patients. The greatest change from baseline to peak were seen in plasma-free hemoglobin (42-fold increase p < 0.01) and the D-dimer:fibrinogen ratio (1.6-fold increase p = 0.03). Bilirubin, carboxyhemoglobin, D-dimer, fibrinogen, and platelets also showed statistically significant changes ( p < 0.01), whereas lactate dehydrogenase did not ( p = 0.93). Progressively deranged hematological markers normalize more than 72 hours after ECMO circuit exchange, with an associated reduction in membrane oxygenator resistance. This supports the biologic plausibility that ECMO circuit exchange may prevent further complications such as hyperfibrinolysis, membrane failure, and clinical bleeding.
Topics: Humans; Extracorporeal Membrane Oxygenation; Hemorrhage; Oxygenators, Membrane; Respiratory Insufficiency
PubMed: 37146593
DOI: 10.1097/MAT.0000000000001976 -
Circulation. Heart Failure Apr 2023Exposure to hyperoxia, a high arterial partial pressure of oxygen (PaO2), may be associated with worse outcomes in patients receiving extracorporeal membrane oxygenator...
BACKGROUND
Exposure to hyperoxia, a high arterial partial pressure of oxygen (PaO2), may be associated with worse outcomes in patients receiving extracorporeal membrane oxygenator (ECMO) support. We examined hyperoxia in the Extracorporeal Life Support Organization Registry among patients receiving venoarterial ECMO for cardiogenic shock.
METHODS
We included Extracorporeal Life Support Organization Registry patients from 2010 to 2020 who received venoarterial ECMO for cardiogenic shock, excluding extracorporeal CPR. Patients were grouped based on PaO2 after 24 hours of ECMO: normoxia (PaO2 60-150 mmHg), mild hyperoxia (PaO2 151-300 mmHg), and severe hyperoxia (PaO2 >300 mmHg). In-hospital mortality was evaluated using multivariable logistic regression.
RESULTS
Among 9959 patients, 3005 (30.2%) patients had mild hyperoxia and 1972 (19.8%) had severe hyperoxia. In-hospital mortality increased across groups: normoxia, 47.8%; mild hyperoxia, 55.6% (adjusted odds ratio, 1.37 [95% CI, 1.23-1.53]; <0.001); severe hyperoxia, 65.4% (adjusted odds ratio, 2.20 [95% CI, 1.92-2.52]; <0.001). A higher PaO2 was incrementally associated with increased in-hospital mortality (adjusted odds ratio, 1.14 per 50 mmHg higher [95% CI, 1.12-1.16]; <0.001). Patients with a higher PaO2 had increased in-hospital mortality in each subgroup and when stratified by ventilator settings, airway pressures, acid-base status, and other clinical variables. In the random forest model, PaO2 was the second strongest predictor of in-hospital mortality, after older age.
CONCLUSIONS
Exposure to hyperoxia during venoarterial ECMO support for cardiogenic shock is strongly associated with increased in-hospital mortality, independent from hemodynamic and ventilatory status. Until clinical trial data are available, we suggest targeting a normal PaO2 and avoiding hyperoxia in CS patients receiving venoarterial ECMO.
Topics: Humans; Shock, Cardiogenic; Hyperoxia; Oxygenators, Membrane; Heart Failure; Oxygen; Hospital Mortality; Hypertension; Retrospective Studies
PubMed: 36871240
DOI: 10.1161/CIRCHEARTFAILURE.122.010328 -
The International Journal of Artificial... May 2023Aim of this work was to characterize possible central anatomical configurations in which a future artificial lung (AL) could be connected, in terms of oxygenation...
OBJECTIVES
Aim of this work was to characterize possible central anatomical configurations in which a future artificial lung (AL) could be connected, in terms of oxygenation performance.
METHODS
Pulmonary and systemic circulations were simulated using a numerical and an in vitro approach. The in vitro simulation was carried out in a mock loop in three phases: (1) normal lung, (2) pulmonary shunt (50% and 100%), and (3) oxygenator support in three anatomical configurations: right atrium-pulmonary artery (RA-PA), pulmonary artery-left atrium (PA-LA), and aorta-left atrium (Ao-LA). The numerical simulation was performed for the oxygenator support phase. The oxygen saturation (SO) of the arterial blood was plotted over time for two percentages of pulmonary shunt and three blood flow rates through the oxygenator.
RESULTS
During the pulmonary shunt phase, SO reached a steady state value (of 68% for a 50% shunt and of nearly 0% for a 100% shunt) 20 min after the shunt was set. During the oxygenator support phase, physiological values of SO were reached for RA-PA and PA-LA, in case of a 50% pulmonary shunt. For the same conditions, Ao-LA could reach a maximum SO of nearly 60%. Numerical results were congruous to the in vitro simulation ones.
CONCLUSIONS
Both in vitro and numerical simulations were able to properly characterize oxygenation properties of a future AL depending on its placement. Different anatomical configurations perform differently in terms of oxygenation. Right to right and right to left connections perform better than left to left ones.
Topics: Lung; Pulmonary Artery; Heart Atria; Oxygenators; Ventilators, Mechanical; Oxygen
PubMed: 37051677
DOI: 10.1177/03913988231168163 -
Journal of Artificial Organs : the... Mar 2024Hollow fiber membrane is incorporated into an extracorporeal membrane oxygenator (ECMO), and the function of the membrane determines the ECMO's functions, such as gas... (Review)
Review
Hollow fiber membrane is incorporated into an extracorporeal membrane oxygenator (ECMO), and the function of the membrane determines the ECMO's functions, such as gas transfer rate, biocompatibility, and durability. In Japan, the membrane oxygenator to assist circulation and ventilation is approved for ECMO support. However, in all cases, the maximum use period has been only 6 h, and so-called 'off-label use' is common for ECMO support of severely ill COVID-19 patients. Under these circumstances, the HLS SET Advanced (Getinge Group Japan K.K.) was approved in 2020 for the first time in Japan as a membrane oxygenator with a two-week period of use. Following this membrane oxygenator, it is necessary to establish a domestic ECMO system that is approved for long-term use and suitable for supporting patients. Looking back on the evolution of ECMO so far, Japanese researchers and manufacturers have also contributed to the developments of ECMO globally. Currently, excellent membrane oxygenators and systems have been marketed by Japanese manufacturers and some of them are globally acclaimed, but in fact, most of the ECMO membranes are not made in Japan. Fortunately, Japan has led the world in the fields of membrane separation technology and hollow fiber membrane production. In the wake of this pandemic, from the perspective of medical and economic security, the practical use of purely domestic hollow fiber membranes and membrane oxygenators for long-term ECMO is imperative in anticipation of the next pandemic.
Topics: Humans; Oxygenators, Membrane; Extracorporeal Membrane Oxygenation; Equipment Design; Japan
PubMed: 36914927
DOI: 10.1007/s10047-023-01389-w -
Cellular and Molecular Life Sciences :... Nov 2009This article outlines the need for a homeostatic response to alterations in cellular oxygenation. It describes work on erythropoietin control that led to the discovery... (Review)
Review
This article outlines the need for a homeostatic response to alterations in cellular oxygenation. It describes work on erythropoietin control that led to the discovery of the hypoxia-inducible transcription factor (HIF-1) and the parallel recognition that this system was responsive to a widespread oxygen-sensing mechanism. Subsequently, multiple HIF isoforms have been shown to have overlapping but non-redundant functions, controlling expression of genes involved in diverse processes such as angiogenesis, vascular tone, metal transport, glycolysis, mitochondrial function, cell growth and survival. The major role of prolyl and asparaginyl hydroxylation in regulating HIFs is described, as well as the identification of PHD1-3 and FIH as the oxygen-sensing enzymes responsible for these hydroxylations. Current understanding of other processes that modulate overall HIF activity, including influences from other signalling mechanisms such as kinases and nitric oxide levels, and the existence of a variety of feedback loops are outlined. The effects of some mutations in this pathway are documented as is knowledge of other substrates for these enzymes. The importance of PHD1-3 and FIH, and the large family of 2-oxoglutarate and iron(II)-dependent dioxygenases of which they are a part, in biology and medicine are discussed.
Topics: Animals; Cell Hypoxia; Humans; Hypoxia-Inducible Factor 1; Mixed Function Oxygenases; Models, Biological; Oxygen; Oxygen Consumption; Protein Isoforms; Transcription Factors
PubMed: 19756382
DOI: 10.1007/s00018-009-0147-7