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The Journal of Physiology May 2021The margin of human viability has extended to the extremes of gestational age (<24 weeks) when the lungs are immature and ventilator-induced lung injury is common....
KEY POINTS
The margin of human viability has extended to the extremes of gestational age (<24 weeks) when the lungs are immature and ventilator-induced lung injury is common. Artificial placenta technology aims to extend gestation ex utero in order to allow the lungs additional time to develop prior to entering an air-breathing environment. We compared the haemodynamics and cerebral oxygenation of piglets in the immediate period post-oxygenator (OXY) transition against both paired in utero measures and uniquely against piglets transitioned onto mechanical ventilation (VENT). Post-transition, OXY piglets became hypotensive with reduced carotid blood flow in comparison with both paired in utero measures and VENT piglets. The addition of a pump to the oxygenator circuit may be required to ensure haemodynamic stability in the immediate post-transition period.
ABSTRACT
Gestational age at birth is a major predictor of wellbeing; the lower the gestational age, the greater the risk of mortality and morbidity. At the margins of human viability (<24 weeks gestation) immature lungs combined with the need for early ventilatory support means lung injury and respiratory morbidity is common. The abrupt haemodynamic changes consequent on birth may also contribute to preterm-associated brain injury, including intraventricular haemorrhage. Artificial placenta technology aims to support oxygenation, haemodynamic stability and ongoing fetal development ex utero until mature enough to safely transition to a true ex utero environment. We aimed to characterize the impact of birth transition onto either an oxygenator circuit or positive pressure ventilation on haemodynamic and cerebral oxygenation of the neonatal piglet. At 112 days gestation (term = 115 days), fetal pigs underwent instrumentation surgery and transitioned onto either an oxygenator (OXY, n = 5) or ventilatory support (VENT, n = 8). Blood pressure (BP), carotid blood flow and cerebral oxygenation in VENT piglets rose from in utero levels to be significantly higher than OXY piglets post-transition. OXY piglet BP, carotid blood flow and carotid oxygen delivery (DO ) decreased from in utero levels post-transition; however, cerebral regional oxygen saturation (rSO ) was maintained at fetal-like levels. OXY piglets became hypoxaemic and retained CO . Whether OXY piglets are able to maintain cerebral rSO under these conditions for a prolonged period is yet to be determined. Improvements to OXY piglet oxygenation may lie in maintaining piglet BP at in utero levels and enhancing oxygenator circuit flow.
Topics: Animals; Female; Gestational Age; Hemodynamics; Lung; Oxygenators; Pregnancy; Respiration, Artificial; Swine
PubMed: 33745149
DOI: 10.1113/JP280803 -
ASAIO Journal (American Society For... 2015Hemolysis can occur as a consequence of extracorporeal membrane oxygenation (ECMO) and is associated with increased mortality and morbidity. Shear stress generated by...
Hemolysis can occur as a consequence of extracorporeal membrane oxygenation (ECMO) and is associated with increased mortality and morbidity. Shear stress generated by flow through the circuit and oxygenator is believed to cause ECMO-induced hemolysis. We hypothesize that either a smaller dimension oxygenator or an in-line hemofilter will increase ECMO-associated hemolysis. Circuits were configured with a Quadrox-D Adult oxygenator (surface area 1.8 m), Quadrox-iD Pediatric oxygenator (surface area 0.8 m), or Quadrox-D Adult oxygenator with an in-line hemofilter (N = 4) and ran for 6 hours. Samples were collected hourly from the ECMO circuit and a time-based hemolysis control. Plasma hemoglobin levels were assayed. Circuit-induced hemolysis at each time point was defined as the change in plasma hemoglobin standardized to the time-based hemolysis control. Plasma hemoglobin increased with the use of the smaller dimension pediatric oxygenator as compared with the adult oxygenator when controlling for ECMO run time (p = 0.02). Furthermore, there was a greater pressure gradient with the smaller dimension pediatric oxygenator (p < 0.05). Plasma hemoglobin did not change with the addition of the in-line hemofilter. The use of a smaller dimension pediatric oxygenator resulted in greater hemolysis and a higher pressure gradient. This may indicate that the increased shear forces augment ECMO-induced hemolysis.
Topics: Adult; Child; Equipment Design; Extracorporeal Membrane Oxygenation; Hemofiltration; Hemoglobins; Hemolysis; Humans; In Vitro Techniques; Oxygenators, Membrane; Plasma; Pressure
PubMed: 25419829
DOI: 10.1097/MAT.0000000000000173 -
The Oncologist 2004Hypoxia is a characteristic feature of locally advanced solid tumors resulting from an imbalance between oxygen (O(2)) supply and consumption. Major causative factors of... (Review)
Review
Hypoxia is a characteristic feature of locally advanced solid tumors resulting from an imbalance between oxygen (O(2)) supply and consumption. Major causative factors of tumor hypoxia are abnormal structure and function of the microvessels supplying the tumor, increased diffusion distances between the nutritive blood vessels and the tumor cells, and reduced O(2) transport capacity of the blood due to the presence of disease- or treatment-related anemia. Tumor hypoxia is a therapeutic concern since it can reduce the effectiveness of radiotherapy, some O(2)-dependent cytotoxic agents, and photodynamic therapy. Tumor hypoxia can also negatively impact therapeutic outcome by inducing changes in the proteome and genome of neoplastic cells that further survival and malignant progression by enabling the cells to overcome nutritive deprivation or to escape their hostile environment. The selection and clonal expansion of these favorably altered cells further aggravate tumor hypoxia and support a vicious circle of increasing hypoxia and malignant progression while concurrently promoting the development of more treatment-resistant disease. This pattern of malignant progression, coupled with the demonstration of a relationship between falling hemoglobin level and worsening tumor oxygenation, highlights the need for effective treatment of anemia as one approach for correcting anemic hypoxia in tumors, and in so doing, possibly improving therapeutic response.
Topics: Adaptation, Physiological; Anemia; Cell Hypoxia; Cell Survival; Cell Transformation, Neoplastic; Disease Progression; Drug Resistance, Neoplasm; Humans; Neoplasms; Neovascularization, Pathologic; Oxygen
PubMed: 15591417
DOI: 10.1634/theoncologist.9-90005-4 -
Anesthesiology Nov 1992
Topics: Humans; Lung Injury; Oxygenators, Membrane; Respiratory Distress Syndrome
PubMed: 1443735
DOI: 10.1097/00000542-199211000-00002 -
Respiratory Medicine May 2021The Coronavirus pandemic has a high mortality rate in patients that are mechanically ventilated, which has led to an ever increasing interest in noninvasive forms of...
BACKGROUND
The Coronavirus pandemic has a high mortality rate in patients that are mechanically ventilated, which has led to an ever increasing interest in noninvasive forms of oxygenation. The use of these devices has the theoretical risk of increased exposure risk because of possible particulate generation. This study aimed to quantify the particulate generation associated with different oxygen devices.
METHODS
This was a prospective single center study conducted during September 2020 using ten healthy adult volunteers. Testing was conducted in a negative pressure hospital room using a light scattering particle counter. The oxygen devices used were a nasal cannula, an OxyMask™, a non-rebreathing mask, and a high flow system. Particle measurements were obtained at baseline in the room and then with each oxygen delivery device and pre-specified oxygen flow rates. These measurements were obtained different distances from the volunteer with their mouth open. A Wilcoxon/Kruskal-Wallis test was performed on each separate oxygen modality with all flow rates as one model.
RESULTS
The particle concentrations were slightly non-significantly increased with the OxyMask™ and non-rebreathing mask at the closest distance measured. As the distance increased, these counts decreased closer to ambient levels. The nasal cannula and high flow nasal cannula particle counts were not significantly different from ambient measurements at either distance.
CONCLUSION
Nasal cannula, OxyMask™, non-rebreathing mask, and high flow oxygen did not generate any additional aerosols or droplets above a baseline room measurement, but further studies are necessary to determine infectious risk.
Topics: Adult; Aerosols; Environmental Exposure; Female; Humans; Male; Oxygenators; Particulate Matter; Respiration, Artificial; Respiratory Therapy
PubMed: 33836331
DOI: 10.1016/j.rmed.2021.106386 -
Experimental Physiology Jan 2003The origin of significant differences between the apparent affinities of heart mitochondrial respiration for exogenous ADP in isolated mitochondria in vitro and in... (Comparative Study)
Comparative Study Review
The origin of significant differences between the apparent affinities of heart mitochondrial respiration for exogenous ADP in isolated mitochondria in vitro and in permeabilized cardiomyocytes or skinned fibres in situ is critically analysed. All experimental data demonstrate the importance of structural factors of intracellular arrangement of mitochondria into functional complexes with myofibrils and sarcoplasmic reticulum in oxidative muscle cells and the control of outer mitochondrial membrane permeability. It has been shown that the high apparent K(m) for exogenous ADP (250-350 mM) in permeabilized cells and in ghost cells (without myosin) and fibres (diameter 15-20 mm) is independent of intrinsic MgATPase activity. However, the K(m) may be decreased significantly by a selective proteolytic treatment, which also destroys the regular arrangement of mitochondria between sarcomeres and increases the accessibility of endogenous ADP to the exogenous pyruvate kinase-phosphoenolpyruvate system. The confocal microscopy was used to study the changes in intracellular distribution of mitochondria and localization of cytoskeletal proteins, such as desmin, tubulin and plectin in permeabilized cardiac cells during short proteolytic treatment. The results show the rapid collapse of microtubular and plectin networks but not of desmin localization under these conditions. These results point to the participation of cytoskeletal proteins in the intracellular organization and control of mitochondrial function in the cells in vivo, where mitochondria are incorporated into functional complexes with sarcomeres and sarcoplasmic reticulum.
Topics: Adenosine Diphosphate; Animals; Ca(2+) Mg(2+)-ATPase; Cell Respiration; Cells, Cultured; Cytoskeleton; Heart; Homeostasis; Microscopy, Confocal; Mitochondria; Muscle Fibers, Skeletal; Myocardium; Myocytes, Cardiac; Oxygen; Rats; Rats, Wistar
PubMed: 12525866
DOI: 10.1113/eph8802511 -
ASAIO Journal (American Society For... Feb 2021Sedation management during extracorporeal membrane oxygenation(ECMO) is a common challenge encountered by treating intensivists. Data about the safety of propofol use... (Observational Study)
Observational Study
Sedation management during extracorporeal membrane oxygenation(ECMO) is a common challenge encountered by treating intensivists. Data about the safety of propofol use during ECMO has been contradictory. We aimed to investigate associated risks of propofol use on oxygenator lifespan and to explore the effect of propofol use on oxygenator membranes when therapeutic anticoagulation was omitted. Adult respiratory ECMO patients who received propofol were retrospectively compared with those who did not, and outcomes were assessed by means of duration of oxygenator functionality before requiring an exchange, and number of exchanges during propofol use and/or ECMO support. Out of the 63patients included in the analysis, 46%received propofol during ECMO as part of sedation regimen. The use of propofol was not found to be associated with an increased incidence of oxygenator failure when compared with cohorts who did not receive propofol (21% propofol arm vs. 6% control, p = 0.13). When analyzed for anticoagulation omission effects, propofol did not increase the risk of oxygenator failure (p = 0.63). The only predictor that statistically predicted the risk of oxygenator failure was development of heparin-induced thrombocytopenia (HIT) during ECMO. The results of this study further support the previously reported safety of propofol utilization during respiratory ECMO even in the absence of anticoagulation.
Topics: Adult; Extracorporeal Membrane Oxygenation; Female; Humans; Hypnotics and Sedatives; Male; Oxygenators, Membrane; Propofol; Prosthesis Failure; Retrospective Studies
PubMed: 32639256
DOI: 10.1097/MAT.0000000000001207 -
Artificial Organs Feb 2018Extracorporeal membrane oxygenation (ECMO) is a life support system that circulates the blood through an oxygenating system to temporarily (days to months) support heart...
Extracorporeal membrane oxygenation (ECMO) is a life support system that circulates the blood through an oxygenating system to temporarily (days to months) support heart or lung function during cardiopulmonary failure until organ recovery or replacement. Currently, the need for high levels of systemic anticoagulation and the risk for bleeding are main drawbacks of ECMO that can be addressed with a redesigned ECMO system. Our lab has developed an approach using microelectromechanical systems (MEMS) fabrication techniques to create novel gas exchange membranes consisting of a rigid silicon micropore membrane (SμM) support structure bonded to a thin film of gas-permeable polydimethylsiloxane (PDMS). This study details the fabrication process to create silicon membranes with highly uniform micropores that have a high level of pattern fidelity. The oxygen transport across these membranes was tested in a simple water-based bench-top set-up as well in a porcine in vivo model. It was determined that the mass transfer coefficient for the system using SµM-PDMS membranes was 3.03 ± 0.42 mL O min m cm Hg with pure water and 1.71 ± 1.03 mL O min m cm Hg with blood. An analytic model to predict gas transport was developed using data from the bench-top experiments and validated with in vivo testing. This was a proof of concept study showing adequate oxygen transport across a parallel plate SµM-PDMS membrane when used as a membrane oxygenator. This work establishes the tools and the equipoise to develop future generations of silicon micropore membrane oxygenators.
Topics: Animals; Diffusion; Dimethylpolysiloxanes; Equipment Design; Extracorporeal Membrane Oxygenation; Oxygen; Oxygenators, Membrane; Permeability; Porosity; Respiratory Insufficiency; Silicon; Swine
PubMed: 28800389
DOI: 10.1111/aor.12972 -
Journal of the American Chemical Society Feb 2023Hypoxia (low oxygen levels) occurs in a range of biological contexts, including plants, bacterial biofilms, and solid tumors; it elicits responses from these biological...
Hypoxia (low oxygen levels) occurs in a range of biological contexts, including plants, bacterial biofilms, and solid tumors; it elicits responses from these biological systems that impact their survival. For example, conditions of low oxygen make treating tumors more difficult and have a negative impact on patient prognosis. Therefore, chemical probes that enable the study of biological hypoxia are valuable tools to increase the understanding of disease-related conditions that involve low oxygen levels, ultimately leading to improved diagnosis and treatment. While small-molecule hypoxia-sensing probes exist, the majority of these image only very severe hypoxia (<1% O) and therefore do not give a full picture of heterogeneous biological hypoxia. Commonly used antibody-based imaging tools for hypoxia are less convenient than small molecules, as secondary detection steps involving immunostaining are required. Here, we report the synthesis, electrochemical properties, photophysical analysis, and biological validation of a range of indolequinone-based bioreductive fluorescent probes. We show that these compounds image different levels of hypoxia in 2D and 3D cell cultures. The resorufin-based probe was activated in conditions of 4% O and lower, while the Me-Tokyo Green-based probe was only activated in severe hypoxia─0.5% O and less. Simultaneous application of these compounds in spheroids revealed that compound images similar levels of hypoxia to pimonidazole, while compound images more extreme hypoxia in a manner analogous to EF5. Compounds and are therefore useful tools to study hypoxia in a cellular setting and represent convenient alternatives to antibody-based imaging approaches.
Topics: Humans; Hypoxia; Neoplasms; Oxygen; Fluorescent Dyes; Cell Hypoxia
PubMed: 36656915
DOI: 10.1021/jacs.2c12493 -
Biological Chemistry 2006Sufficient oxygen supply is crucial for the development and physiology of mammalian cells and tissues. When simple diffusion of oxygen becomes inadequate to provide the... (Review)
Review
Sufficient oxygen supply is crucial for the development and physiology of mammalian cells and tissues. When simple diffusion of oxygen becomes inadequate to provide the necessary flow of substrate, evolution has provided cells with tools to detect and respond to hypoxia by upregulating the expression of specific genes, which allows an adaptation to hypoxia-induced stress conditions. The modulation of cell signaling by hypoxia is an emerging area of research that provides insight into the orchestration of cell adaptation to a changing environment. Cell signaling and adaptation processes are often accompanied by rapid and/or chronic remodeling of membrane lipids by activated lipases. This review highlights the bi-directional relation between hypoxia and lipid signaling mechanisms.
Topics: Animals; Cell Hypoxia; Diglycerides; Humans; Lipid Metabolism; Oxygen; Signal Transduction
PubMed: 17081102
DOI: 10.1515/BC.2006.165