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Molecules (Basel, Switzerland) Dec 2020Oxidative stress-induced lipid peroxidation (LPO) due to neutrophil-derived reactive oxygen species plays a key role in the early stage of the acute respiratory distress...
BACKGROUND
Oxidative stress-induced lipid peroxidation (LPO) due to neutrophil-derived reactive oxygen species plays a key role in the early stage of the acute respiratory distress syndrome (ARDS). Monitoring of oxidative stress in this patient population is of great interest, and, ideally, this can be done noninvasively. Recently, propionaldehyde, a volatile chemical compound (VOC) released during LPO, was identified in the breath of lung transplant recipients as a marker of oxidative stress. The aim of the present study was to identify if markers of oxidative stress appear in the oxygenator outflow gas of patients with severe ARDS treated with veno-venous extracorporeal membrane oxygenation (ECMO).
METHODS
The present study included patients with severe ARDS treated with veno-venous ECMO. Concentrations of acetone, isoprene, and propionaldehyde were measured in inspiratory air, exhaled breath, and oxygenator inflow and outflow gas at corresponding time points. Ion-molecule reaction mass spectrometry was used to measure VOCs in a sequential order within the first 24 h and on day three after ECMO initiation.
RESULTS
Nine patients (5 female, 4 male; age = 42.1 ± 12.2 year) with ARDS and already established ECMO therapy (pre-ECMO PaO/FiO = 44.0 ± 11.5 mmHg) were included into analysis. VOCs appeared in comparable amounts in breath and oxygenator outflow gas (acetone: 838 (422-7632) vs. 1114 (501-4916) ppbv; isoprene: 53.7 (19.5-244) vs. 48.7 (37.9-108) ppbv; propionaldehyde: 53.7 (32.1-82.2) vs. 42.9 (24.8-122) ppbv). Concentrations of acetone, isoprene, and propionaldehyde in breath and oxygenator outflow gas showed a parallel course with time.
CONCLUSIONS
Acetone, isoprene, and propionaldehyde appear in breath and oxygenator outflow gas in comparable amounts. This allows for the measurement of these VOCs in a critically ill patient population via the ECMO oxygenator outflow gas without the need of ventilator circuit manipulation.
Topics: Adolescent; Adult; Aldehydes; Breath Tests; Extracorporeal Membrane Oxygenation; Female; Humans; Male; Middle Aged; Oxygenators; Pilot Projects; Respiration, Artificial; Respiratory Distress Syndrome
PubMed: 33396196
DOI: 10.3390/molecules26010145 -
Brazilian Journal of Cardiovascular... Feb 2023Extracorporeal perfusion flow type requires further investigation. The aim of this study is to compare the effects of pulsatile and nonpulsatile flow on oxygenator... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Extracorporeal perfusion flow type requires further investigation. The aim of this study is to compare the effects of pulsatile and nonpulsatile flow on oxygenator fibers that were analyzed by scanning electron microscope (SEM) and to extensively study patients' coagulation profiles, inflammatory markers, and functional blood tests.
METHODS
Twelve patients who had open heart surgery were randomly divided into two groups; the nonpulsatile flow (group NP, six patients) and pulsatile flow (group P, six patients) groups. Both superficial view and axial sections of the oxygenator fiber samples were examined under SEM to compare the thickness of absorbed blood proteins and amount of blood cells on the surface of oxygenators. Platelet count, coagulation profile, and inflammatory predictors were also studied from the blood samples.
RESULTS
Fibrinogen levels after cardiopulmonary bypass were significantly lower in group NP (group P, 2.57±2.78 g/L; group NP; 2.39±0.70 g/L, P=0.03). Inflammatory biomarkers such as C-reactive protein, interleukin (IL)-6, IL-12, apelin, S100β, and tumor necrosis factor alpha were comparable in both groups. Axial sections of the oxygenator fiber samples had a mean thickness of 45.2 µm and 46.5 µm in groups P and NP, respectively, and this difference is statistically significant (P=0.006). Superficial view of the fiber samples showed obviously lower platelet, leukocyte, and erythrocyte levels in group P.
CONCLUSION
Our study demonstrated that both cellular elements and protein adsorption on oxygenator fibers are lower in the group P than in the group NP. Pulsatile perfusion has better biocompatibility on extracorporeal circulation when analyzed by SEM technique.
Topics: Humans; Oxygenators, Membrane; Pulsatile Flow; Electrons; Extracorporeal Circulation; Cardiopulmonary Bypass; Interleukin-6
PubMed: 35895987
DOI: 10.21470/1678-9741-2021-0519 -
Journal of Cardiac Surgery Dec 2022There continues to be an unmet therapeutic need for an alternative treatment strategy for respiratory distress and lung disease. We are developing a portable...
There continues to be an unmet therapeutic need for an alternative treatment strategy for respiratory distress and lung disease. We are developing a portable cardiopulmonary support system that integrates an implantable oxygenator with a hybrid, dual-support, continuous-flow total artificial heart (TAH). The TAH has a centrifugal flow pump that is rotating about an axial flow pump. By attaching the hollow fiber bundle of the oxygenator to the base of the TAH, we establish a new cardiopulmonary support technology that permits a patient to be ambulatory during usage. In this study, we investigated the design and improvement of the blood flow pathway from the inflow-to-outflow of four oxygenators using a mathematical model and computational fluid dynamics (CFD). Pressure loss and gas transport through diffusion were examined to assess oxygenator design. The oxygenator designs led to a resistance-driven pressure loss range of less than 35 mmHg for flow rates of 1-7 L/min. All of the designs met requirements. The configuration having an outside-to-inside blood flow direction was found to have higher oxygen transport. Based on this advantageous flow direction, two designs (Model 1 and 3) were then integrated with the axial-flow impeller of the TAH for simulation. Flow rates of 1-7 L/min and speeds of 10,000-16,000 RPM were analyzed. Blood damage studies were performed, and Model 1 demonstrated the lowest potential for hemolysis. Future work will focus on developing and testing a physical prototype for integration into the new cardiopulmonary assist system.
Topics: Humans; Equipment Design; Oxygenators; Heart, Artificial; Hemodynamics
PubMed: 36403254
DOI: 10.1111/jocs.17210 -
Scientific Reports Mar 2021Tumors experience temporal and spatial fluctuations in oxygenation. Hypoxia inducible transcription factors (HIF-α) respond to low levels of oxygen and induce re-supply...
Tumors experience temporal and spatial fluctuations in oxygenation. Hypoxia inducible transcription factors (HIF-α) respond to low levels of oxygen and induce re-supply oxygen. HIF-α stabilization is typically facultative, induced by hypoxia and reduced by normoxia. In some cancers, HIF-α stabilization becomes constitutive under normoxia. We develop a mathematical model that predicts how fluctuating oxygenation affects HIF-α stabilization and impacts net cell proliferation by balancing the base growth rate, the proliferative cost of HIF-α expression, and the mortality from not expressing HIF-α during hypoxia. We compare optimal net cell proliferation rate between facultative and constitutive HIF-α regulation in environments with different oxygen profiles. We find that that facultative HIF-α regulation promotes greater net cell proliferation than constitutive regulation with stochastic or slow periodicity in oxygenation. However, cell fitness is nearly identical for both HIF-α regulation strategies under rapid periodic oxygenation fluctuations. The model thus indicates that cells constitutively expressing HIF-α may be at a selective advantage when the cost of expression is low. In cancer, this condition is known as pseudohypoxia or the "Warburg Effect". We conclude that rapid and regular cycling of oxygenation levels selects for pseudohypoxia, and that this is consistent with the ecological theory of optimal defense.
Topics: Cell Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Models, Biological; Oxygen; Protein Stability; Stochastic Processes; Tumor Microenvironment
PubMed: 33707510
DOI: 10.1038/s41598-021-85184-8 -
The British Journal of Radiology Mar 2019Hypoxia is known to be a poor prognostic indicator for nearly all solid tumours and also is predictive of treatment failure for radiotherapy, chemotherapy, surgery and... (Review)
Review
Hypoxia is known to be a poor prognostic indicator for nearly all solid tumours and also is predictive of treatment failure for radiotherapy, chemotherapy, surgery and targeted therapies. Imaging has potential to identify, spatially map and quantify tumour hypoxia prior to therapy, as well as track changes in hypoxia on treatment. At present no hypoxia imaging methods are available for routine clinical use. Research has largely focused on positron emission tomography (PET)-based techniques, but there is gathering evidence that MRI techniques may provide a practical and more readily translational alternative. In this review we focus on the potential for imaging hypoxia by measuring changes in longitudinal relaxation [R; termed oxygen-enhanced MRI or tumour oxygenation level dependent (TOLD) MRI] and effective transverse relaxation [R*; termed blood oxygenation level dependent (BOLD) MRI], induced by inhalation of either 100% oxygen or the radiosensitising hyperoxic gas carbogen. We explain the scientific principles behind oxygen-enhanced MRI and BOLD and discuss significant studies and their limitations. All imaging biomarkers require rigorous validation in order to translate into clinical use and the steps required to further develop oxygen-enhanced MRI and BOLD MRI into decision-making tools are discussed.
Topics: Biomarkers; Contrast Media; Humans; Magnetic Resonance Imaging; Neoplasms; Oxygen; Tumor Hypoxia
PubMed: 30272998
DOI: 10.1259/bjr.20180642 -
American Journal of Physiology. Cell... Sep 2015
Topics: Animals; Cell Hypoxia; Humans; Oxygen
PubMed: 26374688
DOI: 10.1152/ajpcell.zh0-7805-editorial.2015 -
Journal of Cardiothoracic Surgery Mar 2023The management of the oxygenator can be prolonged in the long-term procedures especially during extracorporeal membrane oxygenation (ECMO) for bridge to transplant or...
BACKGROUND
The management of the oxygenator can be prolonged in the long-term procedures especially during extracorporeal membrane oxygenation (ECMO) for bridge to transplant or bridge to recovery. Long-term use often involves an overrun of the time of use with respect to certification of the oxygenating module of 14 days, for the maintenance of performance and efficiency of the oxygenator. The evaluation of the long-term oxygenator efficiency is complex and depends on the: patient pathology, ECMO configuration, the management of coagulation and anticoagulation, materials selection and circuit components, the structure, design and performance of the oxygenator. In this context we investgated the long-term performance of the A.L.ONE Eurosets ECMO oxygenator in relation to the parameters prodromal to replacement.
METHODS
We retrospectively collected eight years data from Anthea Hospital GVM Care & Research, Bari, Italy on the long-term use exceeding 14 days of Eurosets A.L.ONE ECMO Adult oxygenator in Polymetylpentene fiber, for ECMO procedures, including the procedures: Veno Arterial (VA) ECMO post-cardiotomy or not, veno-venous (VV) ECMO. The primary end points were the evaluation of Gas Transfer: oxygen partial pressure (PO) post oxygenator, Carbon dioxide partial pressure (PCO) post oxygenator, the oxygen transfer across the oxygenator membrane V'O, differential CO content across oxygenator; Pressure monitoring: oxygenator pressure Drop in relation to Blood flow rate (BFR) (ΔP); Hematologic values: Hemoglobin, Fibrinogen, Platelets, aPTT, D-Dimer, LDH.
RESULTS
Nine VA ECMO patients who used the oxygenator for 18.5 days and two VV ECMO patients who used the oxygenators for 17.2 days on the seventeenth days reported average values PaO (267 ± 29 mmHg); PaCO (34 ± 4 mmHg) with gas blender values set to 3.8 ± 0.6 L/min of air and a FiO of 78 ± 5%; the transfer across the oxygenator membrane V'O was 189 ± 43 (ml/min/m). The mean peak of partial pressure of carbon dioxide from the gas exhaust of oxygenator (PCO) was 38 ± 4 mmHg; differential CO across the oxygenator "pre-oxygenator PCO-post-oxygenator PCO" (18 ± 6 mmHg); the mean blood flow rate (BFR) 4.5 ± 0.6 (L/minute); the pump revolution per minutes mean maximum rate was 4254 ± 345 (RPM); the mean pressure drop (ΔP) was 76 ± 12 mmHg; the mean peak of d-dimers (DDs) was 23.6 ± 0.8 mg / dL; the mean peak of LDH was 230 ± 55 (mg/dl); fibrinogen mean peak 223 ± 40 (mg/dl).
CONCLUSIONS
The performance of the Eurosets A.L.ONE ECMO Adult polymethylpentene fiber oxygenator in our experience has proven efficiency in terms of O uptake and CO removal, blood fluid dynamics, metabolic compensation and heat exchange in the long-term treatment. The device was safe without iatrogenic problems over a period of 14 days in the patients undergoing ECMO VA and in all patients undergoing VV ECMO with continuous administration of anticoagulation therapy.
Topics: Humans; Adult; Extracorporeal Membrane Oxygenation; Carbon Dioxide; Retrospective Studies; Oxygenators, Membrane; Oxygen
PubMed: 36998079
DOI: 10.1186/s13019-023-02190-9 -
Frontiers in Bioscience (Landmark... Jul 2022This report aims to detail the use of the phosphorescence oxygen analyzer for investigation of thymic responses to pharmaceutical agents, in particular...
BACKGROUND
This report aims to detail the use of the phosphorescence oxygen analyzer for investigation of thymic responses to pharmaceutical agents, in particular immunosuppressants and immunomodulators. Sirolimus (a highly specific inhibitor of the 'molecular target of rapamycin', mTOR) and ozanimod (an agonist of the sphingosine 1-phosphate receptor, recently approved for treatment of multiple sclerosis and ulcerative colitis) are used for this purpose.
METHODS
Thymic fragments from mice were placed in glass vials containing phosphate-buffered saline, bovine albumin, and Pd(II) meso-tetra (sulfophenyl) tetrabenzoporphyrin. The vials were sealed from air, and the cellular oxygen consumption was monitored as function of time.
RESULTS
The decline of dissolved oxygen concentration with time (d[O2]/d) was linear; thus, its rate (thymocyte respiration) was expressed as μM O2 min-1. Cyanide inhibited respiration, confirming the oxygen consumption was in cytochrome oxidase. In age-matched mice, the rate of thymocyte respiration (mean ± SD, in μM O2 min-1 mg-1) was 0.046 ± 0.011 (median = 0.043, range = 0.028 to 0.062, n = 10). In thymic fragments from littermates, this rate was inhibited in the presence of sirolimus (16% lower) or ozanimod (29% lower).
CONCLUSIONS
Thymocyte respiration can serve as a surrogate biomarker for studying the mode-of-action and the cytotoxicity of immunotoxins and immunosuppressants.
Topics: Animals; Cattle; Cell Respiration; Immunosuppressive Agents; Mice; Oxygen; Oxygen Consumption; Sirolimus
PubMed: 36042174
DOI: 10.31083/j.fbl2708230 -
Critical Care (London, England) Apr 2023
Topics: Humans; Extracorporeal Membrane Oxygenation; Oxygenators; Thrombosis; Fibrinolysis; Thrombolytic Therapy
PubMed: 37060093
DOI: 10.1186/s13054-023-04433-6 -
International Journal of Molecular... Dec 2020In eukaryotic algae, respiratory O uptake is enhanced after illumination, which is called light-enhanced respiration (LER). It is likely stimulated by an increase in...
In eukaryotic algae, respiratory O uptake is enhanced after illumination, which is called light-enhanced respiration (LER). It is likely stimulated by an increase in respiratory substrates produced during photosynthetic CO assimilation and function in keeping the metabolic and redox homeostasis in the light in eukaryotic cells, based on the interactions among the cytosol, chloroplasts, and mitochondria. Here, we first characterize LER in photosynthetic prokaryote cyanobacteria, in which respiration and photosynthesis share their metabolisms and electron transport chains in one cell. From the physiological analysis, the cyanobacterium sp. PCC 6803 performs LER, similar to eukaryotic algae, which shows a capacity comparable to the net photosynthetic O evolution rate. Although the respiratory and photosynthetic electron transports share the interchain, LER was uncoupled from photosynthetic electron transport. Mutant analyses demonstrated that LER is motivated by the substrates directly provided by photosynthetic CO assimilation, but not by glycogen. Further, the light-dependent activation of LER was observed even with exogenously added glucose, implying a regulatory mechanism for LER in addition to the substrate amounts. Finally, we discuss the physiological significance of the large capacity of LER in cyanobacteria and eukaryotic algae compared to those in plants that normally show less LER.
Topics: Cell Respiration; Cyanobacteria; Electron Transport; Light; Oxidation-Reduction; Oxygen; Photosynthesis
PubMed: 33396191
DOI: 10.3390/ijms22010342