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Anesthesiology Aug 1977
Review
Topics: Acute Disease; Critical Care; Europe; Heart Ventricles; Hemodynamics; History, 20th Century; Humans; Iatrogenic Disease; Intensive Care Units; Intermittent Positive-Pressure Breathing; Oxygen; Oxygen Inhalation Therapy; Oxygenators, Membrane; Poliomyelitis; Positive-Pressure Respiration; Pulmonary Circulation; Regional Blood Flow; Respiration, Artificial; Respiratory Care Units; Respiratory Insufficiency; United States
PubMed: 327863
DOI: 10.1097/00000542-197708000-00003 -
PloS One 2015This study focusses on the development of a biomimetic oxygenator test device. Due to limited biocompatibility, current oxygenators do not allow mid- to long-term...
OBJECTIVE
This study focusses on the development of a biomimetic oxygenator test device. Due to limited biocompatibility, current oxygenators do not allow mid- to long-term therapy. Tissue engineering uses autologous cell sources to overcome the immunogenic barriers of biomaterials. Surface coating with endothelial cells might improve hemocompatibility and thus prevent immunogenic reactions of the body. In this study this concept is applied to endothelialise a gas-permeable membrane to develop a biomimetic oxygenator test-device (ENDOXY).
METHODS
ENDOXY-a multifunctional test-system was developed to endothelialise a gas-permeable membrane suitable for cell culture and to test the cell retention under shear stress and to measure gas transfer through it.
RESULTS
Successful endothelialisation of the membrane was achieved and cells showed characteristic endothelial morphologies. They stained positive for endothelial markers. The number of cells aligned with shear stress and cell retention after blood perfusing experiments was high. Gas transfer is observed via uncoated and endothelialised membranes.
CONCLUSION
The study showed promising results with regard to system design, endothelialisation, and cell retention under shear stress conditions. It strongly encourages further research into the system by testing different membrane materials to design a biomimetic membrane surface and pave way for a fully hemocompatible oxygenator.
Topics: Biomimetic Materials; Endothelial Cells; Equipment Design; Materials Testing; Oxygenators, Membrane; Stress, Mechanical; Tissue Engineering
PubMed: 26682907
DOI: 10.1371/journal.pone.0142961 -
Molecular Cell Dec 2017Physiologic and environmental factors can modulate antibiotic activity and thus pose a significant challenge to antibiotic treatment. The quinolone class of antibiotics,...
Physiologic and environmental factors can modulate antibiotic activity and thus pose a significant challenge to antibiotic treatment. The quinolone class of antibiotics, which targets bacterial topoisomerases, fails to kill bacteria that have grown to high density; however, the mechanistic basis for this persistence is unclear. Here, we show that exhaustion of the metabolic inputs that couple carbon catabolism to oxidative phosphorylation is a primary cause of growth phase-dependent persistence to quinolone antibiotics. Supplementation of stationary-phase cultures with glucose and a suitable terminal electron acceptor to stimulate respiratory metabolism is sufficient to sensitize cells to quinolone killing. Using this approach, we successfully sensitize high-density populations of Escherichia coli, Staphylococcus aureus, and Mycobacterium smegmatis to quinolone antibiotics. Our findings link growth-dependent quinolone persistence to discrete impairments in respiratory metabolism and identify a strategy to kill non-dividing bacteria.
Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Carbon; Cell Respiration; Drug Resistance, Bacterial; Microbial Sensitivity Tests; Oxidative Phosphorylation; Oxygen; Quinolones
PubMed: 29225037
DOI: 10.1016/j.molcel.2017.11.012 -
The New Phytologist Feb 2011Temperature crucially affects the speed of metabolic processes in poikilotherm organisms, including plants. The instantaneous temperature responses of O(2)-reduction and... (Review)
Review
Temperature crucially affects the speed of metabolic processes in poikilotherm organisms, including plants. The instantaneous temperature responses of O(2)-reduction and CO(2)-release can be approximated by Arrhenius kinetics, even though respiratory gas exchange of plants is the net effect of many constituent biochemical processes. Nonetheless, the classical Arrhenius equation must be modified to account for a dynamic response to measurement temperatures. We show that this dynamic response is readily explained by combining Arrhenius and Michaelis-Menten kinetics, as part of a fresh appraisal of metabolic interpretations of instantaneous temperature responses. In combination with recent experimental findings, we argue that control of mitochondrial electron flow is shared among cytochrome oxidase and alternative oxidase under in vivo conditions, and is continuously coordinated. In this way, upstream carbohydrate metabolism and downstream electron transport appear to be optimized according to the demand of ATP, TCA-cycle intermediates and anabolic reducing power under differing metabolic states. We provide a link to the 'Growth and Maintenance Paradigm' of respiration and argue that respiratory temperature responses can be used as a tool to probe metabolic states of plant tissue, such that we can learn more about the mechanisms that govern longer-term acclimatization responses of plant metabolism.
Topics: Acclimatization; Carbohydrate Metabolism; Carbon Dioxide; Cell Respiration; Energy Metabolism; Mitochondria; Oxidoreductases; Oxygen; Plants; Stress, Physiological; Temperature
PubMed: 21223283
DOI: 10.1111/j.1469-8137.2010.03576.x -
Optics Letters Aug 2019Hypoxia, a low tissue oxygenation condition caused by insufficient oxygen supply, leads to potentially irreversible tissue damage, such as brain infarction during...
Hypoxia, a low tissue oxygenation condition caused by insufficient oxygen supply, leads to potentially irreversible tissue damage, such as brain infarction during stroke. Intravascular oxygenation has long been used by photoacoustic imaging, among other imaging modalities, to study hypoxia. However, intravascular oxygenation describes only the oxygen supply via microcirculation, which does not directly reflect the amount of free oxygen available for metabolism in the interstitial fluid. Therefore, to fully understand hypoxia, it is highly desirable to monitor blood oxygenation as well as tissue oxygenation during the same biological process. In this work, by combining high-resolution photoacoustic microscopy (PAM) and a novel bioreducible N-oxide-based hypoxia-sensitive probe HyP-650, we have demonstrated simultaneous imaging of intravascular oxygenation and tissue hypoxia. We have established detailed chemical, optical, and photoacoustic properties of HyP-650 for hypoxic activation in vitro and in living cells. We have also performed PAM on hindlimb ischemia models and tumor-bearing mice to study the correlation between intravascular oxygenation and tissue oxygenation at various hypoxic levels. We expect that Hyp-650 enhanced photoacoustic imaging will find a variety of applications in brain and cancer research.
Topics: Animals; Blood Vessels; Hindlimb; Ischemia; Mice; Microscopy; Oxygen; Photoacoustic Techniques; Tumor Hypoxia
PubMed: 31368965
DOI: 10.1364/OL.44.003773 -
The Journal of Biological Chemistry Jan 2007The protein complexes of the mitochondrial oxidative phosphorylation system were recently reported to form supramolecular assemblies termed respiratory supercomplexes or... (Review)
Review
The protein complexes of the mitochondrial oxidative phosphorylation system were recently reported to form supramolecular assemblies termed respiratory supercomplexes or respirasomes. These supercomplexes are considered to be of great functional importance. Here we review new insights into supercomplex structure and physiology.
Topics: Animals; Arabidopsis; Biochemistry; Cell Respiration; Chlamydomonas; Electron Transport; Electron Transport Chain Complex Proteins; Eukaryota; Mitochondria; Models, Biological; Oxidative Phosphorylation; Oxygen; Plant Physiological Phenomena; Plant Proteins; Submitochondrial Particles
PubMed: 17102127
DOI: 10.1074/jbc.R600031200 -
International Journal of Nanomedicine 2018Hypoxia exists to some degree in most solid tumors due to inadequate oxygen delivery of the abnormal vasculature which cannot meet the demands of the rapidly... (Review)
Review
Hypoxia exists to some degree in most solid tumors due to inadequate oxygen delivery of the abnormal vasculature which cannot meet the demands of the rapidly proliferating cancer cells. The levels of oxygenation within the same tumor are highly variable from one area to another and can change over time. Tumor hypoxia is an important impediment to effective cancer therapy. In radiotherapy, the primary mechanism is the creation of reactive oxygen species; hypoxic tumors are therefore radiation resistant. A number of chemotherapeutic drugs have been shown to be less effective when exposed to a hypoxic environment which can lead to further disease progression. Hypoxia is also a potent barrier to effective immunotherapy in cancer treatment. Because of the recognition of hypoxia as an important barrier to cancer treatment, a variety of approaches have been undertaken to overcome or reverse tumor hypoxia. Such approaches have included breathing hyperbaric oxygen, artificial hemoglobins, allosteric hemoglobin modifiers, hypoxia activated prodrugs and fluorocarbons (FCs). These approaches have largely failed due to limited efficacy and/or adverse side effects. Oxygen therapeutics, based on liquid FCs, can potentially increase the oxygen-carrying capacity of the blood to reverse tumor hypoxia. Currently, at least two drugs are in clinical trials to reverse tumor hypoxia; one of these is designed to improve permeability of oxygen into the tumor tissue and the other is based upon a low boiling point FC that transports higher amounts of oxygen per gram than previously tested FCs.
Topics: Animals; Cell Hypoxia; Humans; Immunotherapy; Neoplasms; Oxygen; Radiation-Sensitizing Agents; Tumor Hypoxia
PubMed: 30323592
DOI: 10.2147/IJN.S140462 -
Biochimica Et Biophysica Acta.... Aug 2017Tumor hypoxia has long been considered as a detrimental factor for the response to irradiation. In order to improve the sensitivity of tumors cells to radiation therapy,... (Review)
Review
Manipulation of tumor oxygenation and radiosensitivity through modification of cell respiration. A critical review of approaches and imaging biomarkers for therapeutic guidance.
Tumor hypoxia has long been considered as a detrimental factor for the response to irradiation. In order to improve the sensitivity of tumors cells to radiation therapy, tumor hypoxia may theoretically be alleviated by increasing the oxygen delivery or by decreasing the oxygen consumption by tumor cells. Mathematical modelling suggested that decreasing the oxygen consumption should be more efficient than increasing oxygen delivery in order to alleviate tumor hypoxia. In this paper, we review several promising strategies targeting the mitochondrial respiration for which alleviation of tumor hypoxia and increase in sensitivity to irradiation have been demonstrated. Because the translation of these approaches into the clinical arena requires the use of pharmacodynamics biomarkers able to identify shift in oxygen consumption and tumor oxygenation, we also discuss the relative merits of imaging biomarkers (Positron Emission Tomography and Magnetic Resonance) that may be used for therapeutic guidance. This article is part of a Special Issue entitled Mitochondria in Cancer, edited by Giuseppe Gasparre, Rodrigue Rossignol and Pierre Sonveaux.
Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Biomarkers, Tumor; Cell Hypoxia; Combined Modality Therapy; Humans; Hyperbaric Oxygenation; Mitochondria; Neoplasm Proteins; Neoplasms; Oxygen; Oxygen Consumption; Radiation Tolerance; Tumor Microenvironment; Uncoupling Agents; Xenograft Model Antitumor Assays
PubMed: 28088332
DOI: 10.1016/j.bbabio.2017.01.002 -
Hematic Antegrade Repriming Reduces Emboli on Cardiopulmonary Bypass: A Randomized Controlled Trial.ASAIO Journal (American Society For... Mar 2023Particulate and gaseous microemboli (GME) are side effects of cardiac surgery that interfere with postoperative recovery by causing endothelial dysfunction and vascular... (Randomized Controlled Trial)
Randomized Controlled Trial
Particulate and gaseous microemboli (GME) are side effects of cardiac surgery that interfere with postoperative recovery by causing endothelial dysfunction and vascular blockages. GME sources during surgery are multiple, and cardiopulmonary bypass (CPB) is contributory to this embolic load. Hematic antegrade repriming (HAR) is a novel procedure that combines the benefits of repriming techniques with additional measures, by following a standardized procedure to provide a reproducible hemodilution of 300 ml. To clarify the safety of HAR in terms of embolic load delivery, a prospective and controlled study was conducted, by applying Doppler probes to the extracorporeal circuit, to determine the number and volume of GME released during CPB. A sample of 115 patients (n = 115) was considered for assessment. Both groups were managed under strict normothermia, and similar clinical conditions and protocols, receiving the same open and minimized circuit. Significant differences in GME volume delivery (control group [CG] = 0.28 ml vs. HAR = 0.08 ml; p = 0.004) and high embolic volume exposure (>1 ml) were found between the groups (CG = 30.36% vs. HAR = 4.26%; p = 0.001). The application of HAR did not represent an additional embolic risk and provided a four-fold reduction in the embolic volume delivered to the patient (coefficient, 0.24; 95% CI, 0.08-0.72; p = 0.01), which appears to enhance GME clearance of the oxygenator before CPB initiation.
Topics: Humans; Cardiopulmonary Bypass; Embolism, Air; Prospective Studies; Equipment Design; Oxygenators
PubMed: 35609139
DOI: 10.1097/MAT.0000000000001776 -
The Journal of Extra-corporeal... Sep 2022We present a 62-year-old patient with COVID-19 pneumonia on Veno-venous (VV) Extracorporeal Membrane Oxygenation (ECMO) with unique perturbations to pre and post...
We present a 62-year-old patient with COVID-19 pneumonia on Veno-venous (VV) Extracorporeal Membrane Oxygenation (ECMO) with unique perturbations to pre and post oxygenator pressures due to fibrin deposition in despite being on a Heparin/Bivalirudin infusion and activated Partial Thromboplastin Time (aPTT) within therapeutic range of 60-80 seconds. On Day 8 of ECMO support, it was noticed that flows steadily decreased despite unchanged RPMs. Unlike typical blood flow to circuit pressure relationships, the circuit pressures did not correlate with the observed decreased flow. The Delta Pressure (Δ) was not elevated. The patient's vitals were stable. On inspection post change-out, clots were noted in the oxygenator outlets. Oxygenator clots are usually associated with increased Δ. In this scenario, clots in the oxygenator blocked 1 of the 4 outlets in the oxygenator causing the flow, pressures, and Δ to drop consecutively. Due to reduced flow, the Δ was not elevated despite extensive clots. The fibrin clot location in the CardioHelp ECMO circuit may lead to unexpected pressure and flow alterations. Sole reliance on Δ as a marker for oxygenator clots may be misleading. Careful monitoring and timely diagnosis of coagulation status may lead to changes in anticoagulation goals and meaningfully impact patient outcomes.
Topics: Humans; Middle Aged; COVID-19; Oxygenators; Thrombosis; Extracorporeal Membrane Oxygenation; Fibrin
PubMed: 36742210
DOI: 10.1182/ject-239-241