-
Cardiovascular Engineering and... Apr 2022Extracorporeal membrane oxygenation has gained increasing attention in the treatment of patients with acute and chronic cardiopulmonary and respiratory failure. However,...
PURPOSE
Extracorporeal membrane oxygenation has gained increasing attention in the treatment of patients with acute and chronic cardiopulmonary and respiratory failure. However, clotting within the oxygenators or other components of the extracorporeal circuit remains a major complication that necessitates at least a device exchange and bears risks of adverse events for the patients. In order to better predict thrombus growth within oxygenators, we present an approach for in-vitro visualization of thrombus growth using real-time X-ray imaging.
METHODS
An in-vitro test setup was developed using low-dose anticoagulated ovine blood and allowing for thrombus growth within 4 h. The setup was installed in a custom-made X-ray setup that uses phase-contrast for imaging, thus providing enhanced soft-tissue contrast, which improves the differentiation between blood and potential thrombus growth. During experimentation, blood samples were drawn for the analysis of blood count, activated partial thromboplastin time and activated clotting time. Additionally, pressure and flow data was monitored and a full 360° X-ray scan was performed every 15 min.
RESULTS
Thrombus formation indicated by a pressure drop and changing blood parameters was monitored in all three test devices. Red and white thrombi (higher/lower attenuation, respectively) were successfully segmented in one set of X-ray images.
CONCLUSION
We showed the feasibility of a new in-vitro method for real-time thrombus growth visualization by means of phase contrast X-ray imaging. In addition, with more blood parameters that are clinically relevant, this approach might contribute to improved oxygenator exchange protocols in the clinical routine.
Topics: Animals; Extracorporeal Membrane Oxygenation; Feasibility Studies; Humans; Lung; Oxygenators, Membrane; Sheep; Thrombosis; X-Rays
PubMed: 34532837
DOI: 10.1007/s13239-021-00579-y -
Free Radical Biology & Medicine Dec 2017Molecular oxygen is one of the most important variables in modern cell culture systems. Fluctuations in its concentration can affect cell growth, differentiation,... (Review)
Review
Molecular oxygen is one of the most important variables in modern cell culture systems. Fluctuations in its concentration can affect cell growth, differentiation, signaling, and free radical production. In order to maintain culture viability, experimental validity, and reproducibility, it is imperative that oxygen levels be consistently maintained within physiological "normoxic" limits. Use of the term normoxia, however, is not consistent among scientists who experiment in cell culture. It is typically used to describe the atmospheric conditions of a standard incubator, not the true microenvironment to which the cells are exposed. This error may lead to the situation where cells grown in a standard "normoxic" oxygen concentration may actually be experiencing a wide range of conditions ranging from hyperoxia to near-anoxic conditions at the cellular level. This apparent paradox is created by oxygen's sluggish rate of diffusion through aqueous medium, and the generally underappreciated effects that cell density, media volume, and barometric pressure can have on pericellular oxygen concentration in a cell culture system. This review aims to provide an overview of this phenomenon we have termed "consumptive oxygen depletion" (COD), and includes a basic review of the physics, potential consequences, and alternative culture methods currently available to help circumvent this largely unrecognized problem.
Topics: Cell Count; Cell Culture Techniques; Cell Differentiation; Cell Hypoxia; Cell Proliferation; Cells, Cultured; Diffusion; Humans; Hyperoxia; Oxygen; Oxygen Consumption; Reproducibility of Results; Translational Research, Biomedical
PubMed: 29032224
DOI: 10.1016/j.freeradbiomed.2017.10.003 -
ASAIO Journal (American Society For... Jun 2023Recently three different neonatal extracorporeal membrane oxygenation (ECMO) circuits have been employed in our clinic. These circuits were compared for clotting and...
Recently three different neonatal extracorporeal membrane oxygenation (ECMO) circuits have been employed in our clinic. These circuits were compared for clotting and bleeding complications. Initially, we used an ECMO circuit containing a roller pump and venous bladder without severe complications. Manufacturing of circuit components was discontinued, necessitating the replacement of this circuit by a circuit with a centrifugal pump with 3/8 inch inlet and outlet. Acute increase of oxygenator resistance requiring emergency changeout became unexpectedly a regularly occurring complication. The increase in resistance was suspected to be caused by oxygenator clotting, although oxygenator function was preserved. To prevent this complication, we changed to a levitating centrifugal pump with 1/4 inch inlet and outlet, after which no oxygenator malfunction has been observed. Macroscopic and electron microscopic analysis demonstrates that small clots are formed within the circuit, presumably in or near the centrifugal pump, which are transported to the oxygenator and clog up the hollow fiber layer at the inlet side, barely penetrating the oxygenator beyond this first layer. Our results suggest that low blood velocities accompanied with recirculation of blood within or near the centrifugal pump and/or heat generation within the pump could contribute to the formation of these clots.
Topics: Humans; Infant, Newborn; Blood Coagulation; Extracorporeal Membrane Oxygenation; Hemostatics; Thrombosis; Oxygenators, Membrane
PubMed: 36574471
DOI: 10.1097/MAT.0000000000001878 -
Free Radical Biology & Medicine Jan 2019Molecular oxygen, reactive oxygen species and free radicals derived from oxygen play important roles in a broad spectrum of physiological and pathological processes. The...
Molecular oxygen, reactive oxygen species and free radicals derived from oxygen play important roles in a broad spectrum of physiological and pathological processes. The quantitative measurement of molecular oxygen in tissues by electron paramagnetic resonance (EPR) has great potential for understanding and diagnosing a number of diseases, and for developing and guiding therapies. This requires improvements in the free radical probe systems that sense and report molecular oxygen levels in vivo. We report on the encapsulation of existing free radical probes in lipophilic gel implants: an in-situ-oleogel and an emulgel, based only on well-known, safe excipients for the incorporation of lipophilic and hydrophilic radicals, respectively. The EPR signals of encapsulated radicals were not altered compared to dissolved radicals. The high solubility of oxygen in lipophilic solvents enhanced oxygen sensitivity. The gels extended the lifetime of the radicals in tissues from tens of minutes to many days, simplifying studies with extended series of measurements. The encapsulated radicals showed a good in vivo response to changes in oxygen supply and seem to circumvent concerns from toxicity of the radical probes. These gels simplify the development of new oxygen-sensitive free radical probes for EPR oximetry by making their in vivo stability, persistence and toxicity a function of the encapsulating gel and not a set of additional requirements for the free radical probe.
Topics: Animals; Cell Respiration; Cells, Cultured; Electron Spin Resonance Spectroscopy; Female; Free Radicals; Hydrophobic and Hydrophilic Interactions; Mice; Mice, Inbred C3H; Muscles; Organic Chemicals; Oximetry; Oxygen; Reactive Oxygen Species; Trityl Compounds
PubMed: 30416100
DOI: 10.1016/j.freeradbiomed.2018.10.442 -
The New Phytologist May 2011The oxygen availability to plant tissues can vary strongly in time and space. To endure short- or long-term oxygen deprivation, plants evolved a series of metabolic and... (Review)
Review
The oxygen availability to plant tissues can vary strongly in time and space. To endure short- or long-term oxygen deprivation, plants evolved a series of metabolic and morphological adaptations that have been extensively studied. However, our knowledge of the molecular regulation of these processes is not as well understood. In this review, the recent findings on the molecular effectors that regulate the response of higher plants to oxygen deficiency are discussed. Although no direct oxygen sensor has been discovered in plants so far, mechanisms that perceive low-oxygen derived signals have been reported, involving different sets of transcription factors (TFs). The ERF (Ethylene Responsive Factor) family especially appears to play a crucial role in the determination of survival to reduced oxygen availability in Arabidopsis and rice. This class of TFs displays a broad range of targets, being involved in both the metabolic reprogramming and the morphological adaptations exploited by plants when subjected to low-oxygen conditions.
Topics: Adaptation, Physiological; Cell Hypoxia; Models, Biological; Oxygen; Plants; Signal Transduction
PubMed: 21091695
DOI: 10.1111/j.1469-8137.2010.03562.x -
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 -
The Journal of Extra-corporeal... Jun 2012This report describes the assessment of three specific safety-related specifications in the consideration of an alternate oxygenator; first the grip strength...
This report describes the assessment of three specific safety-related specifications in the consideration of an alternate oxygenator; first the grip strength relationship between various oxygenator connectors and SMARxT tubing, second, the grip strength of various biopassive tubings and an isolated SMARxT connector, and finally, the accuracy of the arterial outlet temperature measurement. Grip strength experiments for the connections between the SMARxT tubing and the venous reservoir outlet and the oxygenator venous inlet and oxygenator arterial outlet of the Medtronic Affinity, Sorin Synthesis, Sorin Primox, and Terumo Capiox RX25 oxygenators were performed. In addition we compared the grip strength of polyvinyl chloride, Physio, Trillium, Carmeda, X-Coating, and SMARxT tubing. The accuracy of the integrated arterial outlet temperature probes was determined by comparing the temperatures measured by the integrated probe with a precision reference thermometer. Connector grip strength comparisons for the evaluation oxygenators with SMARxT tubing showed significant variation between oxygenators and connections (p = .02). Evaluation of the arterial outlet showed significant variation between evaluation oxygenators, while at the venous reservoir outlet and oxygenator inlet, there were no significant differences. Grip strength comparison data for the various tubing types demonstrated a main effect for tubing type F(5, 18) = 8.01, p = .002, eta(p)(2) = .77. Temperature accuracy measurements demonstrated that all oxygenators overread the arterial outlet temperature at 15 degrees C, whilst at temperatures > or = 25 degrees C, all oxygenators underread the arterial outlet temperature. The integrity of SMARxT tubing connection is influenced by the connector type, and may decline over time, highlighting the importance to not consider interchanging components of the bypass circuit as inconsequential.
Topics: Body Temperature; Cardiopulmonary Bypass; Catheters, Indwelling; Equipment Safety; Extracorporeal Membrane Oxygenation; Hand Strength; Humans; Oxygenators; Thermometers; Validation Studies as Topic
PubMed: 22893983
DOI: No ID Found -
The Journal of Neuroscience : the... Jul 2015In terrestrial mammals, the oxygen storage capacity of the CNS is limited, and neuronal function is rapidly impaired if oxygen supply is interrupted even for a short...
In terrestrial mammals, the oxygen storage capacity of the CNS is limited, and neuronal function is rapidly impaired if oxygen supply is interrupted even for a short period of time. However, oxygen tension monitored by the peripheral (arterial) chemoreceptors is not sensitive to regional CNS differences in partial pressure of oxygen (PO2 ) that reflect variable levels of neuronal activity or local tissue hypoxia, pointing to the necessity of a functional brain oxygen sensor. This experimental animal (rats and mice) study shows that astrocytes, the most numerous brain glial cells, are sensitive to physiological changes in PO2 . Astrocytes respond to decreases in PO2 a few millimeters of mercury below normal brain oxygenation with elevations in intracellular calcium ([Ca(2+)]i). The hypoxia sensor of astrocytes resides in the mitochondria in which oxygen is consumed. Physiological decrease in PO2 inhibits astroglial mitochondrial respiration, leading to mitochondrial depolarization, production of free radicals, lipid peroxidation, activation of phospholipase C, IP3 receptors, and release of Ca(2+) from the intracellular stores. Hypoxia-induced [Ca(2+)]i increases in astrocytes trigger fusion of vesicular compartments containing ATP. Blockade of astrocytic signaling by overexpression of ATP-degrading enzymes or targeted astrocyte-specific expression of tetanus toxin light chain (to interfere with vesicular release mechanisms) within the brainstem respiratory rhythm-generating circuits reveals the fundamental physiological role of astroglial oxygen sensitivity; in low-oxygen conditions (environmental hypoxia), this mechanism increases breathing activity even in the absence of peripheral chemoreceptor oxygen sensing. These results demonstrate that astrocytes are functionally specialized CNS oxygen sensors tuned for rapid detection of physiological changes in brain oxygenation. Significance statement: Most, if not all, animal cells possess mechanisms that allow them to detect decreases in oxygen availability leading to slow-timescale, adaptive changes in gene expression and cell physiology. To date, only two types of mammalian cells have been demonstrated to be specialized for rapid functional oxygen sensing: glomus cells of the carotid body (peripheral respiratory chemoreceptors) that stimulate breathing when oxygenation of the arterial blood decreases; and pulmonary arterial smooth muscle cells responsible for hypoxic pulmonary vasoconstriction to limit perfusion of poorly ventilated regions of the lungs. Results of the present study suggest that there is another specialized oxygen-sensitive cell type in the body, the astrocyte, that is tuned for rapid detection of physiological changes in brain oxygenation.
Topics: Animals; Astrocytes; Cell Hypoxia; Cells, Cultured; Chemoreceptor Cells; Immunohistochemistry; Male; Mice; Mice, Knockout; Organ Culture Techniques; Oxygen; Rats; Rats, Sprague-Dawley; Respiratory Physiological Phenomena
PubMed: 26203141
DOI: 10.1523/JNEUROSCI.0045-15.2015 -
Advanced Science (Weinheim,... Apr 2023Tumor hypoxia drives resistance to many cancer therapies, including radiotherapy and chemotherapy. Methods that increase tumor oxygen pressures, such as hyperbaric...
Tumor hypoxia drives resistance to many cancer therapies, including radiotherapy and chemotherapy. Methods that increase tumor oxygen pressures, such as hyperbaric oxygen therapy and microbubble infusion, are utilized to improve the responses to current standard-of-care therapies. However, key obstacles remain, in particular delivery of oxygen at the appropriate dose and with optimal pharmacokinetics. Toward overcoming these hurdles, gas-entrapping materials (GeMs) that are capable of tunable oxygen release are formulated. It is shown that injection or implantation of these materials into tumors can mitigate tumor hypoxia by delivering oxygen locally and that these GeMs enhance responsiveness to radiation and chemotherapy in multiple tumor types. This paper also demonstrates, by comparing an oxygen (O )-GeM to a sham GeM, that the former generates an antitumorigenic and immunogenic tumor microenvironment in malignant peripheral nerve sheath tumors. Collectively the results indicate that the use of O -GeMs is promising as an adjunctive strategy for the treatment of solid tumors.
Topics: Humans; Oxygen; Neoplasms; Hyperbaric Oxygenation; Tumor Hypoxia; Tumor Microenvironment
PubMed: 36727291
DOI: 10.1002/advs.202205995 -
Anesthesiology Apr 1977
Review
Topics: Carbon Dioxide; Carotid Arteries; Catheterization; Embolism, Amniotic Fluid; Female; Femoral Artery; Femoral Vein; Hemodynamics; Humans; Oxygen Consumption; Oxygenators, Membrane; Pregnancy; Pulmonary Circulation; Respiratory Insufficiency; Silicones
PubMed: 320912
DOI: 10.1097/00000542-197704000-00008