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Critical Care (London, England) Apr 2021
Topics: Carboxyhemoglobin; Equipment and Supplies Utilization; Extracorporeal Membrane Oxygenation; Hemolysis; Humans; Oxygenators
PubMed: 33906676
DOI: 10.1186/s13054-021-03582-w -
The Journal of Extra-corporeal... Mar 2005A clinically relevant rat cardiopulmonary bypass (CPB) model would be a valuable tool for investigating pathophysiological and therapeutic strategies on bypass. Previous...
A clinically relevant rat cardiopulmonary bypass (CPB) model would be a valuable tool for investigating pathophysiological and therapeutic strategies on bypass. Previous rat CPB models have been described in the literature; however, they have many limitations, including large circuit surface area, the inability to achieve full bypass, and donor blood requirements for prime. Therefore, we have established a rat CPB model designed to overcome these limitations. The miniature circuit consisted of a filtered reservoir, heat exchanger, membrane oxygenator (surface area = 0.02 m2) with a static priming volume of 2.8 mL, and an inline blood gas monitor. The circuit was primed with 9.5+/-0.5 mL of crystalloid solution and CPB was established on male Sprague-Dawley rats (430-475 g, n = 5) by cannulating the left common carotid artery and the right external jugular vein. The animals were placed on CPB at full flow (111+/-13 mL/kg/ min) for 1 hour and were monitored for and additional 2 hours after the CPB procedure. Hemodynamics, hemoglobin concentration (Hb), and blood gases were analyzed at three time intervals: before, during, and after CPB. The circuit performance was evaluated according to prime volume, compliance, hemodynamic parameters, and gas and heat exchange as described by modified AMMI standards. Data are expressed as mean+/-SD and a repeated-measures analysis of variance with post-Hoc test was used for data comparison between the three time intervals. The ratio of oxygenator surface area to subject body weight for this model is comparable with that of current human adult CPB practice (0.05 m2/kg vs 0.057 m2/kg) Full CPB was achieved and we observed clinically acceptable PaO2, PaCO2, and SvO2 values (209+/-86 mmHg, 25+/-2 mmHg, 78+/-8%, respectively) while on CPB. The use of asanguinous prime did produce statistically significant Hg reduction (15.7+/-0.76 vs. 9.2+/-0.59 g/dL) comparable with clinical practice. No statistically significant differences between pre- and post-CPB hemodynamics and blood gases were found in our study. We have established a miniature circuit consisting of asanquineous prime for a rat CPB model that maintains clinically acceptable results regarding hemodynamic parameters, blood gases, and hemodilution. This model would be valuable for further use in clinically relevant research studies.
Topics: Animals; Carbon Dioxide; Cardiopulmonary Bypass; Extracorporeal Membrane Oxygenation; Models, Animal; Oxygen; Oxygenators, Membrane; Rats; Rats, Sprague-Dawley
PubMed: 15804160
DOI: No ID Found -
The Journal of Extra-corporeal... Mar 2020Creation of water condensation in blood oxygenators is a phenomenon that is constantly present during cardiopulmonary bypass and in medium- to long-term extracorporeal...
Creation of water condensation in blood oxygenators is a phenomenon that is constantly present during cardiopulmonary bypass and in medium- to long-term extracorporeal life support. Clinical observation of condensation at the oxygenator exit is still a common event normally associated with sudden cooling of the gas flow proximal to the outlet cover (after exiting the fiber bundle), where the warming effect of blood is no longer present. Condensation could progressively obstruct a certain number of fibers, reducing the efficiency of gaseous exchange in the membrane of the oxygenator surface. The study included 48 patients divided into four oxygenator groups of 12 each: group 1 used an Inspire 6 F oxygenator from Livanova; group 2, an Affinity Fusion from Medtronic; group 3, an Alone from Eurosets, and group 4, an ECMO Alone from Eurosets; while the last group used an ECMO Alone oxygenator from Eurosets with polymethylpentene fiber. Each group of oxygenators comprising 12 patients were divided into two groups, namely, A and B, with six patients in each group. Group A used mild hypothermia during the procedure, and group B of six patients used normothermia; Groups A and B were further subdivided into four subgroups: A1, A2, B1, and B2, each consists of three patients; subgroups A1 and B1 used negative aspiration (-8 mmHg) measuring humidity (%) and temperature (°C) in the gas oxygenator output; consequently, a measurement system was necessary to be created; Subgroups A2 and B2 did not use negative aspiration in the oxygenator outlet. No statistically significant difference for PaO and humidity values was found in polypropylene and polymethylpentene oxygenators with mild hypothermia management with vacuum and without vacuum in the gas outlet in the first 60 minutes and 60 minutes later during cardiopulmonary bypass. In normothermia, a statistically significant difference in the PaO-humidity relationship was observed with polypropylene and polymethylpentene fiber models. Results of this study show an inversely proportional correlation between gas exchange and condensation in statistically significant values during the use of normothermia and a reduction in oxygenation performance, in polypropylene and polymethylpentene fiber oxygenators.
Topics: Aged; Cardiopulmonary Bypass; Equipment Design; Extracorporeal Membrane Oxygenation; Humans; Oxygen; Oxygenators; Oxygenators, Membrane; Water
PubMed: 32280143
DOI: 10.1182/ject-1900028 -
The Journal of Thoracic and... Jul 2020
Topics: Extracorporeal Membrane Oxygenation; Heart-Lung Machine; Lung Transplantation; Oxygenators, Membrane; Reperfusion
PubMed: 31959446
DOI: 10.1016/j.jtcvs.2019.11.037 -
PloS One 2014Hypoxia influences many key biological functions. In cancer, it is generally believed that hypoxic condition is generated deep inside the tumor because of the lack of...
Hypoxia influences many key biological functions. In cancer, it is generally believed that hypoxic condition is generated deep inside the tumor because of the lack of oxygen supply. However, consumption of oxygen by cancer should be one of the key means of regulating oxygen concentration to induce hypoxia but has not been well studied. Here, we provide direct evidence of the mitochondrial role in the induction of intracellular hypoxia. We used Acetylacetonatobis [2-(2'-benzothienyl) pyridinato-kN, kC3'] iridium (III) (BTP), a novel oxygen sensor, to detect intracellular hypoxia in living cells via microscopy. The well-differentiated cancer cell lines, LNCaP and MCF-7, showed intracellular hypoxia without exogenous hypoxia in an open environment. This may be caused by high oxygen consumption, low oxygen diffusion in water, and low oxygen incorporation to the cells. In contrast, the poorly-differentiated cancer cell lines: PC-3 and MDAMB231 exhibited intracellular normoxia by low oxygen consumption. The specific complex I inhibitor, rotenone, and the reduction of mitochondrial DNA (mtDNA) content reduced intracellular hypoxia, indicating that intracellular oxygen concentration is regulated by the consumption of oxygen by mitochondria. HIF-1α was activated in endogenously hypoxic LNCaP and the activation was dependent on mitochondrial respiratory function. Intracellular hypoxic status is regulated by glucose by parabolic dose response. The low concentration of glucose (0.045 mg/ml) induced strongest intracellular hypoxia possibly because of the Crabtree effect. Addition of FCS to the media induced intracellular hypoxia in LNCaP, and this effect was partially mimicked by an androgen analog, R1881, and inhibited by the anti-androgen, flutamide. These results indicate that mitochondrial respiratory function determines intracellular hypoxic status and may regulate oxygen-dependent biological functions.
Topics: Biosensing Techniques; Blotting, Western; Cell Hypoxia; Cell Line, Tumor; Cell Respiration; Coordination Complexes; Glucose; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Microscopy, Confocal; Mitochondria; Neoplasms; Oxygen; Rotenone
PubMed: 24586439
DOI: 10.1371/journal.pone.0088911 -
The British Journal of Cancer.... Jul 1996The 40-year history of hypoxic cell sensitisation can be traced from hyperbaric oxygen to the present clinical studies with carbogen, nicotinamide and accelerated... (Review)
Review
The 40-year history of hypoxic cell sensitisation can be traced from hyperbaric oxygen to the present clinical studies with carbogen, nicotinamide and accelerated radiotherapy. A meta-analysis by Overgaard (1995) included 10703 cases entered into 83 randomised controlled trials and showed an overall improvement in local tumour control of 4.6% (P = 0.00001) and in survival of 2.8% (P = 0.005). Hyperbaric oxygen gave a 6.6% (P = 0.003) improvement in local control and hypoxic cell sensitisers 3.9% (P = 0.04). Despite this, the only hypoxic cell-sensitising method in routine clinical use is the giving of nimorazole in supraglottic and pharyngeal carcinomas. Acute, as well as chronic hypoxia has been recognised and nicotinamide, the amide derivative of B3 is believed to prevent the former. Thus ARCON (accelerated radiotherapy, carbogen and nicotinamide) has been introduced in the clinic in an effort to overcome tumour proliferation, chronic and acute hypoxia, respectively. The success of future randomised controlled trials would be improved greatly if methods were available to measure the concentration of hypoxic cells in tumours before treatment and thus select those where benefit may be gained. The use of ARCON recognises that tumour cell proliferation is an important cause of failure in addition to hypoxia. However, intrinsic radiosensitivity may also need to be taken into account in the future. Clinical trials aim to improve the therapeutic ratio and thus the study of morbidity is as important as local tumour control. International collaboration is essential if randomised controlled trials are to be carried out within reasonable periods of time.
Topics: Blood Transfusion; Carbon Dioxide; Cell Hypoxia; Humans; Hyperbaric Oxygenation; Neoplasms; Niacinamide; Oxygen; Radiation-Sensitizing Agents
PubMed: 8763896
DOI: No ID Found -
PLoS Computational Biology Jul 2021Radiologic images provide a way to monitor tumor development and its response to therapies in a longitudinal and minimally invasive fashion. However, they operate on a...
Radiologic images provide a way to monitor tumor development and its response to therapies in a longitudinal and minimally invasive fashion. However, they operate on a macroscopic scale (average value per voxel) and are not able to capture microscopic scale (cell-level) phenomena. Nevertheless, to examine the causes of frequent fast fluctuations in tissue oxygenation, models simulating individual cells' behavior are needed. Here, we provide a link between the average data values recorded for radiologic images and the cellular and vascular architecture of the corresponding tissues. Using hybrid agent-based modeling, we generate a set of tissue morphologies capable of reproducing oxygenation levels observed in radiologic images. We then use these in silico tissues to investigate whether oxygen fluctuations can be explained by changes in vascular oxygen supply or by modulations in cellular oxygen absorption. Our studies show that intravascular changes in oxygen supply reproduce the observed fluctuations in tissue oxygenation in all considered regions of interest. However, larger-magnitude fluctuations cannot be recreated by modifications in cellular absorption of oxygen in a biologically feasible manner. Additionally, we develop a procedure to identify plausible tissue morphologies for a given temporal series of average data from radiology images. In future applications, this approach can be used to generate a set of tissues comparable with radiology images and to simulate tumor responses to various anti-cancer treatments at the tissue-scale level.
Topics: Cell Hypoxia; Computational Biology; Computer Simulation; Humans; Mathematical Concepts; Models, Biological; Neoplasms; Oxygen; Radiography; Systems Analysis; Tumor Hypoxia; Tumor Microenvironment
PubMed: 34310608
DOI: 10.1371/journal.pcbi.1009206 -
Pigment Cell & Melanoma Research Apr 2009The tissue microenvironment plays a critical role in cell survival and growth and can contribute to cell transformation and tumor development. Cellular interactions with... (Review)
Review
The tissue microenvironment plays a critical role in cell survival and growth and can contribute to cell transformation and tumor development. Cellular interactions with the stroma and with other cells provide key signals that control cellular arrest or division, survival or death, and entrance or exit from a quiescent state. Together, these decisions are essential for maintenance of tissue homeostasis. Tissue oxygenation is an important component of the microenvironment that can acutely alter the behavior of a cell through the direct regulation of genes involved in cell survival, apoptosis, glucose metabolism, and angiogenesis. Loss of tissue homeostasis due to, for example, oncogene activation leads to the disruption of these signals and eventually can lead to cell transformation and tumor development. Here we review the role of tissue oxygenation, and in particular physiologic skin hypoxia, on cell survival and senescence and how it contributes to melanocyte transformation and melanoma development.
Topics: Animals; Cell Hypoxia; Cell Survival; Humans; Melanocytes; Melanoma; Oxygen; Skin
PubMed: 19222803
DOI: 10.1111/j.1755-148X.2009.00553.x -
Biochemical and Biophysical Research... Aug 2005By oxymetry and electron paramagnetic resonance (EPR), we investigated the effects of repeated anoxia/re-oxygenation (A/R) periods on the respiration and production of...
By oxymetry and electron paramagnetic resonance (EPR), we investigated the effects of repeated anoxia/re-oxygenation (A/R) periods on the respiration and production of free radicals by synoviocytes (rabbit HIG-82 cell line and primary equine synoviocytes) and equine articular chondrocytes. Three periods of 20 min anoxia followed by re-oxygenation were applied to 10(7)cells; O(2) consumption was measured before anoxia and after each re-oxygenation. After the last A/R, cellular free radical formation was investigated by EPR spectroscopy with spin trapping technique (n=3 for each cell line). Both types of synoviocytes showed a high O(2) consumption, which was slowered after anoxia. By EPR with the spin trap POBN, we proved a free radical formation. Results were similar for equine and rabbit synoviocytes. For chondrocytes, we observed a low O(2) consumption, unchanged by anoxia, and no free radical production. These observations suggest an oxidant activity of synoviocytes, potentially important for the onset of osteoarthritis.
Topics: Animals; Cartilage, Articular; Cell Hypoxia; Cells, Cultured; Chondrocytes; Free Radicals; Horses; Oxygen; Oxygen Consumption; Rabbits; Reactive Oxygen Species; Synovial Membrane
PubMed: 16036131
DOI: 10.1016/j.bbrc.2005.06.147 -
Plant Signaling & Behavior Jul 2020Membrane lipids change drastically in plants when they suffered from hypoxia (oxygen deficiency) stress. Overall, hypoxia stress lowers the contents of total lipids,...
Membrane lipids change drastically in plants when they suffered from hypoxia (oxygen deficiency) stress. Overall, hypoxia stress lowers the contents of total lipids, inhabits lipid biosynthesis, and stimulates lipid degradation, leading to the accumulation of free fatty acids. Lipid alterations include changes in the contents of lipid classes, the extent of saturation, and the length of acyl chains. But the detail and systematic studies about lipid changes, as well as the function mechanism in hypoxia stress are poorly understood. Here, the major unanswered questions and suggestions on the study of the function of lipid in hypoxia stress were provided.
Topics: Cell Hypoxia; Lipid Metabolism; Membrane Lipids; Oxygen
PubMed: 32463337
DOI: 10.1080/15592324.2020.1771938