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Cellular and Molecular Life Sciences :... Nov 2009This article outlines the need for a homeostatic response to alterations in cellular oxygenation. It describes work on erythropoietin control that led to the discovery... (Review)
Review
This article outlines the need for a homeostatic response to alterations in cellular oxygenation. It describes work on erythropoietin control that led to the discovery of the hypoxia-inducible transcription factor (HIF-1) and the parallel recognition that this system was responsive to a widespread oxygen-sensing mechanism. Subsequently, multiple HIF isoforms have been shown to have overlapping but non-redundant functions, controlling expression of genes involved in diverse processes such as angiogenesis, vascular tone, metal transport, glycolysis, mitochondrial function, cell growth and survival. The major role of prolyl and asparaginyl hydroxylation in regulating HIFs is described, as well as the identification of PHD1-3 and FIH as the oxygen-sensing enzymes responsible for these hydroxylations. Current understanding of other processes that modulate overall HIF activity, including influences from other signalling mechanisms such as kinases and nitric oxide levels, and the existence of a variety of feedback loops are outlined. The effects of some mutations in this pathway are documented as is knowledge of other substrates for these enzymes. The importance of PHD1-3 and FIH, and the large family of 2-oxoglutarate and iron(II)-dependent dioxygenases of which they are a part, in biology and medicine are discussed.
Topics: Animals; Cell Hypoxia; Humans; Hypoxia-Inducible Factor 1; Mixed Function Oxygenases; Models, Biological; Oxygen; Oxygen Consumption; Protein Isoforms; Transcription Factors
PubMed: 19756382
DOI: 10.1007/s00018-009-0147-7 -
Redox Biology May 2024Mitochondrial respiration extends beyond ATP generation, with the organelle participating in many cellular and physiological processes. Parallel changes in components of...
Mitochondrial respiration extends beyond ATP generation, with the organelle participating in many cellular and physiological processes. Parallel changes in components of the mitochondrial electron transfer system with respiration render it an appropriate hub for coordinating cellular adaption to changes in oxygen levels. How changes in respiration under functional hypoxia (i.e., when intracellular O levels limit mitochondrial respiration) are relayed by the electron transfer system to impact mitochondrial adaption and remodeling after hypoxic exposure remains poorly defined. This is largely due to challenges integrating findings under controlled and defined O levels in studies connecting functions of isolated mitochondria to humans during physical exercise. Here we present experiments under conditions of hypoxia in isolated mitochondria, myotubes and exercising humans. Performing steady-state respirometry with isolated mitochondria we found that oxygen limitation of respiration reduced electron flow and oxidative phosphorylation, lowered the mitochondrial membrane potential difference, and decreased mitochondrial calcium influx. Similarly, in myotubes under functional hypoxia mitochondrial calcium uptake decreased in response to sarcoplasmic reticulum calcium release for contraction. In both myotubes and human skeletal muscle this blunted mitochondrial adaptive responses and remodeling upon contractions. Our results suggest that by regulating calcium uptake the mitochondrial electron transfer system is a hub for coordinating cellular adaption under functional hypoxia.
Topics: Humans; Calcium; Oxygen Consumption; Cell Respiration; Hypoxia; Muscle, Skeletal; Oxygen
PubMed: 38401291
DOI: 10.1016/j.redox.2024.103037 -
Perfusion May 2023The novel Capiox NX19 adult oxygenator is, compared to its predecessors, improved with enhanced air removal technology, a polymer heat exchanger and smaller, innovative...
INTRODUCTION
The novel Capiox NX19 adult oxygenator is, compared to its predecessors, improved with enhanced air removal technology, a polymer heat exchanger and smaller, innovative hollow fibers resulting in a surface area reduction and a lower priming volume. The aim of this study was to evaluate the NX19 oxygenator performance in a clinical setting.
METHODS
A prospective multicenter study was performed involving three large European university hospitals. The Capiox NX19 ( = 150) performance was assessed during adult cardiopulmonary bypass and involved gaseous microemboli handling and gas transfer efficiency. The heat exchanger performance was evaluated separately in vitro.
RESULTS
The heat exchanger performance factors were 0.80 ± 0.03 and 0.58 ± 0.04 at pump flow rates of 3 L/min and 6 L/min, respectively. After priming, residual post-oxygenator gaseous microemboli count and volume were decreased by 91% and 93.7%, respectively. The gas compartment pressure was 6.0 ± 2.5 mmHg, while the O transfer was 69 ± 30 mL/min/m and the CO transfer 73 ± 34 mL/min/m. The O gradient was 44 ± 19 mmHg/LPM and the O diffusing capacity 0.38 ± 0.14 mL/min/mmHg. The shunt fraction was 0.19 ± 0.13, whereas oxygenator resistance and shear stress were 10.5 ± 3.7 mmHg/LPM and 5.1 ± 3.1 dyn/cm, respectively.
CONCLUSION
This multicenter study displayed good clinical safety and performance of the NX19 oxygenator.
Topics: Adult; Humans; Oxygenators, Membrane; Prospective Studies; Equipment Design; Extracorporeal Membrane Oxygenation; Cardiopulmonary Bypass; Gases
PubMed: 35348392
DOI: 10.1177/02676591221078942 -
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 -
ASAIO Journal (American Society For... Jul 2023Membrane oxygenator failure during venovenous (V-V) extracorporeal membrane oxygenation (ECMO) can lead to life-threatening hypoxia, high replacement costs, and may be...
Membrane oxygenator failure during venovenous (V-V) extracorporeal membrane oxygenation (ECMO) can lead to life-threatening hypoxia, high replacement costs, and may be associated with a hyperfibrinolytic state and bleeding. The current understanding of the underlying mechanisms that drive this is limited. The primary aim of this study therefore is to investigate the hematological changes that occur before and after membrane oxygenator and circuit exchanges (ECMO circuit exchange) in patients with severe respiratory failure managed on V-V ECMO. We analyzed 100 consecutive V-V ECMO patients using linear mixed-effects modeling to evaluate hematological markers in the 72 hours before and 72 hours after ECMO circuit exchange. A total of 44 ECMO circuit exchanges occurred in 31 of 100 patients. The greatest change from baseline to peak were seen in plasma-free hemoglobin (42-fold increase p < 0.01) and the D-dimer:fibrinogen ratio (1.6-fold increase p = 0.03). Bilirubin, carboxyhemoglobin, D-dimer, fibrinogen, and platelets also showed statistically significant changes ( p < 0.01), whereas lactate dehydrogenase did not ( p = 0.93). Progressively deranged hematological markers normalize more than 72 hours after ECMO circuit exchange, with an associated reduction in membrane oxygenator resistance. This supports the biologic plausibility that ECMO circuit exchange may prevent further complications such as hyperfibrinolysis, membrane failure, and clinical bleeding.
Topics: Humans; Extracorporeal Membrane Oxygenation; Hemorrhage; Oxygenators, Membrane; Respiratory Insufficiency
PubMed: 37146593
DOI: 10.1097/MAT.0000000000001976 -
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 -
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 -
Biochimica Et Biophysica Acta Apr 2012The reactions between Complex IV (cytochrome c oxidase, CcOX) and nitric oxide (NO) were described in the early 60's. The perception, however, that NO could be... (Review)
Review
BACKGROUND
The reactions between Complex IV (cytochrome c oxidase, CcOX) and nitric oxide (NO) were described in the early 60's. The perception, however, that NO could be responsible for physiological or pathological effects, including those on mitochondria, lags behind the 80's, when the identity of the endothelial derived relaxing factor (EDRF) and NO synthesis by the NO synthases were discovered. NO controls mitochondrial respiration, and cytotoxic as well as cytoprotective effects have been described. The depression of OXPHOS ATP synthesis has been observed, attributed to the inhibition of mitochondrial Complex I and IV particularly, found responsible of major effects.
SCOPE OF REVIEW
The review is focused on CcOX and NO with some hints about pathophysiological implications. The reactions of interest are reviewed, with special attention to the molecular mechanisms underlying the effects of NO observed on cytochrome c oxidase, particularly during turnover with oxygen and reductants.
MAJOR CONCLUSIONS AND GENERAL SIGNIFICANCE
The NO inhibition of CcOX is rapid and reversible and may occur in competition with oxygen. Inhibition takes place following two pathways leading to formation of either a relatively stable nitrosyl-derivative (CcOX-NO) of the enzyme reduced, or a more labile nitrite-derivative (CcOX-NO(2)(-)) of the enzyme oxidized, and during turnover. The pathway that prevails depends on the turnover conditions and concentration of NO and physiological substrates, cytochrome c and O(2). All evidence suggests that these parameters are crucial in determining the CcOX vs NO reaction pathway prevailing in vivo, with interesting physiological and pathological consequences for cells.
Topics: Animals; Cell Respiration; Cytochromes c; Electron Transport Complex IV; Humans; Models, Biological; Nitric Oxide; Oxidation-Reduction; Oxygen; Signal Transduction
PubMed: 21939634
DOI: 10.1016/j.bbabio.2011.09.002 -
Revista Brasileira de Cirurgia... 2015To provide a brief review of the development of cardiopulmonary bypass. (Review)
Review
OBJECTIVE
To provide a brief review of the development of cardiopulmonary bypass.
METHODS
A review of the literature on the development of extracorporeal circulation techniques, their essential role in cardiovascular surgery, and the complications associated with their use, including hemolysis and inflammation.
RESULTS
The advancement of extracorporeal circulation techniques has played an essential role in minimizing the complications of cardiopulmonary bypass, which can range from various degrees of tissue injury to multiple organ dysfunction syndrome. Investigators have long researched the ways in which cardiopulmonary bypass may insult the human body. Potential solutions arose and laid the groundwork for development of safer postoperative care strategies.
CONCLUSION
Steady progress has been made in cardiopulmonary bypass in the decades since it was first conceived of by Gibbon. Despite the constant evolution of cardiopulmonary bypass techniques and attempts to minimize their complications, it is still essential that clinicians respect the particularities of each patient's physiological function.
Topics: Biomarkers; Cardiopulmonary Bypass; Cytokines; Equipment Design; Heart-Lung Machine; Hemolysis; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Oxygenators
PubMed: 26107456
DOI: 10.5935/1678-9741.20150021 -
Cell Sep 2016The 2016 Albert Lasker Basic Medical Research Award is being awarded to Gregg Semenza, William Kaelin, and Peter Ratcliffe for discovery of the pathway by which human...
The 2016 Albert Lasker Basic Medical Research Award is being awarded to Gregg Semenza, William Kaelin, and Peter Ratcliffe for discovery of the pathway by which human and animal cells sense and adapt to changes in oxygen availability-an essential requirement for survival. Bill and Peter joined Cell editor João Monteiro in an informal conversation about science, medicine, designing experiments, and training the next generation.
Topics: Animals; Awards and Prizes; Cell Hypoxia; Humans; Oxygen
PubMed: 27634317
DOI: 10.1016/j.cell.2016.08.048