Changes In Oxygen Tension Research Articles

Endometriosis development in relation to hypoxia: a murine model study.

Endometriosis, due to its ambiguous symptoms, still remains one of the most difficult female diseases to treat, with an average diagnosis time of 7-9years. The changing level of hypoxia plays an important role in a healthy endometrium during menstruation and an elevated expression of the hypoxia-inducible factor 1-alpha (HIF-1α) has been demonstrated in ectopic endometria. HIF-1α mediates the induction of proangiogenic factors and the development of angiogenesis is a critical step in the establishment and pathogenesis of endometriosis. Although the inhibition of angiogenesis has been proposed as one of the actionable therapeutic modalities, vascular normalization and re-oxygenation may become a possible new approach for therapeutic intervention. Our goal was to investigate whether a selected murine model of endometriosis would be suitable for future studies on new methods for treating endometriosis. Non-invasive, high-resolution ultrasound-monitored observation was selected as the preclinical approach to obtain imaging of the presence and volume of the endometriotic-like lesions. The EF5 (2-(2-Nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide) compound that selectively binds to reduced proteins in hypoxic cells was used for hypoxia detection. The expression of Pten and other crucial genes linking endometriosis and hypoxia were also assessed. Using EF5, a pentafluorinated derivative of the 2-nitroimidazole that is metabolically reduced by oxygen-inhibitable nitroreductase, we confirmed that hypoxia did develop in the selected model and was detected in uterine and ectopic endometriotic lesions. Moreover, the changes in oxygen tension also influenced the expression level of significant genes related to endometriosis, like Pten, Trp53, Hif1a, Epas1, and Vegfa. Their strong modulation evidenced here is indicative of model reliability. Using high-resolution ultrasound-based imaging, we present a non-invasive method of visualization that enables the detection and observation of lesion evolution throughout the duration of the experiment, which is fundamental for further preclinical studies and treatment evaluation. The selected model and method of visualization appear to be suitable for the study of new treatment strategies based on hypoxia alleviation and blood flow restoration.

Glucose deprivation impairs hypoxia-inducible factor-1α synthesis

Hypoxia-inducible factors (HIFs) are key transcriptional mediators of the hypoxic response and are implicated in oncogenesis. HIFα is regulated by a well-characterized, oxygen-dependent degradation pathway involving the von Hippel Lindau (VHL) tumor suppressor protein. However, comparatively little is known about HIFα regulation at the translational level, particularly under cellular stress. There is evidence that HIFα expression not only responds to changes in oxygen tension, but also nutrient availability. In this study, we monitored global translation rates, ATP levels and HIF1α synthesis rates in response to glucose starvation or glycolysis inhibition. We found that both global and HIF1α-specific translation rates decline under glucose deprivation that is concomitant with ATP reduction. These results are in contrast with previous reports showing preferential HIF1α synthesis despite global translation suppression under hypoxia and suggest that a glucose requirement in cellular metabolism is associated with HIF1α translation.

Organ chips with integrated multifunctional sensors enable continuous metabolic monitoring at controlled oxygen levels

Despite remarkable advances in Organ-on-a-chip (Organ Chip) microfluidic culture technology, recreating tissue-relevant physiological conditions, such as the region-specific oxygen concentrations, remains a formidable technical challenge, and analysis of tissue functions is commonly carried out using one analytical technique at a time. Here, we describe two-channel Organ Chip microfluidic devices fabricated from polydimethylsiloxane and gas impermeable polycarbonate materials that are integrated with multiple sensors, mounted on a printed circuit board and operated using a commercially available Organ Chip culture instrument. The novelty of this system is that it enables the recreation of physiologically relevant tissue-tissue interfaces and oxygen tension as well as non-invasive continuous measurement of transepithelial electrical resistance, oxygen concentration and pH, combined with simultaneous analysis of cellular metabolic activity (ATP/ADP ratio), cell morphology, and tissue phenotype. We demonstrate the reliable and reproducible functionality of this system in living human Gut and Liver Chip cultures. Changes in tissue barrier function and oxygen tension along with their functional and metabolic responses to chemical stimuli (e.g., calcium chelation, oligomycin) were continuously and noninvasively monitored on-chip for up to 23 days. A physiologically relevant microaerobic microenvironment that supports co-culture of human intestinal cells with living Lactococcus lactis bacteria also was demonstrated in the Gut Chip. The integration of multi-functional sensors into Organ Chips provides a robust and scalable platform for the simultaneous, continuous, and non-invasive monitoring of multiple physiological functions that can significantly enhance the comprehensive and reliable evaluation of engineered tissues in Organ Chip models in basic research, preclinical modeling, and drug development.

Fructose vs. glucose: modulating stem cell growth and function through sugar supplementation.

In multicellular organisms, stem cells are impacted by microenvironmental resources such as nutrient availability and oxygen tension for their survival, growth, and differentiation. However, the accessibility of these resources in the pericellular environment greatly varies from organ to organ. This divergence in resource availability leads to variations in the potency and differentiation potential of stem cells. This study aimed to explore the distinct effects of glucose and fructose, as well as different oxygen tensions, on the growth dynamics, cytokine production, and differentiation of stem cells. We showed that replacing glucose with fructose subjected stem cells to stress, resulting in increased Hif1α expression and stability, which in turn led to a reduction in cell proliferation, and alterations in cytokine production. However, fructose failed to induce differentiation of human mesenchymal stem cells (hMSCs) as well as mouse fibroblasts into mature adipocytes compared to glucose, despite the upregulation of key markers of adipogenesis, including C/EBPβ, and PPARγ. Conversely, we showed that fructose induced undifferentiated mouse fibroblasts to release cytokines associated with senescence, including IL1α1, IL6, IL8, MCP1, and TNF1α, suggesting that these cells were undergoing lipolysis. Taken together, our results suggest that altering the culture conditions through changes in hexose levels and oxygen tension places considerable stress on stem cells. Additional research is required to further characterize the mechanisms governing stem cell response to their microenvironments.

Hypoxia Exposure Fine-Tunes Mitochondrial Function in Primary Dermal Fibroblasts Derived from Loggerhead Sea Turtles

Sea turtles are constantly exposed to changes in oxygen tension derived from extended breath-hold diving, but the cellular-level response to such changes is not completely understood. Most studies in hypoxia-tolerant reptiles have focused on the freshwater turtle Trachemys scripta, which responds to anoxia by inducing metabolic rewiring and preserving mitochondrial integrity, facilitating effcient mitochondrial respiration during reoxygenation. Here, we derived primary dermal fibroblasts from loggerhead sea turtles and western fence lizards to study the bioenergetic cellular response to hypoxia exposure in diving and non-diving reptiles. Cells from both species stained positive for the fibroblast markers vimentin and PDGFRb and responded to hypoxia exposure (0.1% O2) by accumulating HIF-1α. We measured oxygen consumption rates (OCR) in intact cells using Seahorse technology. We found that basal, maximal, and spare respiratory capacity was lower in lizard than in loggerhead cells at 26oC under normoxic (room air) conditions (p < 0.0001). Exposure to short (1h) and long-term hypoxia (24h) altered mitochondrial function in both species. Maximal and spare respiratory capacity were lower in loggerhead than in lizard cells (p < 0.01) after 1h hypoxia followed by 1h reoxygenation. In contrast, basal and maximal respiratory capacity was higher in loggerhead compared to lizard cells after 24h hypoxia (p < 0.04). Nonetheless, the overall OCR after 24h hypoxia in both species was lower than that observed after 1h hypoxia. Overall, there was a significant reduction in cellular respiration in both species from short-term to long-term hypoxia exposure. In lizard cells, basal OCR decreased by a factor of three while maximal OCR decreased by a factor of 4.5. In loggerhead cells, both the basal and maximal OCR decreased by a factor of two. Our results demonstrate species-specific regulation of cellular respiration after hypoxia exposure. Remarkably, loggerhead cells show a steady downregulation of cellular respiration in response to hypoxia exposure and faster recovery after extended hypoxia (24h) than lizard cells, aligning with the remarkable hypoxic tolerance exhibited by sea turtles, which can endure up to 7 hours of breath-holding underwater. Understanding the cellular mechanisms that drive hypoxic tolerance in diving animals can provide insights for treating human conditions characterized by hypoxia signaling. Ford Foundation. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The Role of Hypoxia Inducible Factor (HIF) 1α in the Pathogenesis of Liver Cirrhosis: A Narrative Literature Review

The small changes in oxygen tension that occur during viral hepatitis, metabolic disorders, steatohepatitis, inflammation, and carcinogenesis are sufficient to increase hypoxic response, namely an increase in HIF. HIF is a protein that belongs to the PAS (period circadian protein-aryl hydrocarbon receptor nuclear translocator-single-minded protein) family. HIF regulates the adaptation of cells to oxygen. HIF is a transcription factor containing α and β subunits. The expression of the α subunit is oxygen-dependent, while the β subunit is expressed continuously and independently of oxygen. HIFs regulate various signaling events by binding to specific DNA sequences known as hypoxia response elements (HREs) in target genes, leading to an increase or decrease in their transcription. HIF-1α is a key regulator of hypoxia signaling.

THE CATALYTIC PROPERTIES OF LACTATE DEHYDROGENASE IN SKELETAL MUSCLES AND LIVER OF THE MARSH FROG (PELOPHYLAX RIDIBUNDUS) DEPEND ON ITS ECOLOGICAL AND GEOGRAPHICAL LOCATION

The marsh frog (Pelophylax ridibundus) has a widespread distribution range, which is due to a variety of adaptations that contribute to the development of tolerance to a wide range of physicochemical environmental factors. Of particular interest are the adaptations of these animals to different levels of oxygen in mid- and high-altitude conditions. In this work, a comparative analysis of the kinetic parameters of lactate dehydrogenase (LDH) in the liver of marsh frogs living in the mountainous and lowland regions of Dagestan was carried out. Animals caught in their habitats were decapitated, the liver and calf muscles were isolated, and they were placed in liquid nitrogen. In the laboratory, the selected tissues were homogenized and mitochondria-free cytosol was obtained by differential centrifugation, in which LDH activity was determined. It was found that LDH activity is significantly higher in the tissues of frogs from mountainous regions: by 42.4% in the muscles and 2.38 times in the liver (p 0.05). The high efficiency of catalysis is ensured due to significant changes in the catalytic parameters of the enzyme: an increase in Vmax (50.9% in muscles and 70% in the liver (p 0.05)) and a decrease in Km. (45.9% in muscles and 69% in liver, (p 0.05)). A more pronounced difference, compared to muscles, between LDH activity in the liver of foothill and lowland populations of frogs suggests that the sensitivity of liver LDH to changes in oxygen tension is higher. The vector of a number of other kinetic parameters of LDH (Ki, Sopt, Δ) in the liver of animals from mountainous landscapes is absolutely opposite to that of skeletal muscles. High activity and modifications of the catalytic properties of LDH in the tissues of marsh frogs living in mid-mountain areas may play an important role in the adaptation of these animals to conditions of oxygen deficiency.

Abstract 26 The Role of Oxygen in Cord Blood Hematopoietic Stem and Progenitor Cell Expansion and Engraftment

Abstract Introduction Hematopoietic stem (HSC) and progenitor cells (HPCs) are exposed to differing oxygen tensions ranging from <1% to 21% as they reside in/move through different tissues or are harvested for clinical utility. Functional changes in HSCs/HPCs are induced by acute changes in oxygen tension (e.g., a change in percent of cells in cycle). Objectives We sought to determine if variable oxygen levels affect expansion and/or functional properties of cord blood (CB) HSCs/HPCs ex vivo and in vivo. Methods Human CB CD34+ cells were grown in expansion culture +/-UM171, an agonist of HSC self-renewal that expands transplantable CB HSCs, in five oxygen tensions: 1%O2, 3%O2, 5%O2, 14%O2, and 21%O2. HSCs/HPCs were enumerated by flow cytometry. Functional HPCs were enumerated by plating in semi solid media for colony forming unit assays (CFU). Cell cycle and reactive oxygen species (ROS) were measured by flow cytometry. Ability of expanded cells to engraft was determined by transplantation in non-lethally irradiated NSG mice. Results Immunophenotypic HPCs and functional HPC CFUs expanded significantly more after 7 days of growth in higher oxygen tensions (5%O2-21%O2) compared to lower (1%O2-3%O2), while immunophenotypic HSCs expanded best at 5% O2. HSCs/HPCs grown in low oxygen tensions had significantly lower ROS levels, significantly higher percentage of cells in G0, and were slightly but reproducibly smaller/less granular than those grown in high oxygen levels. HSC/HPC numbers were reduced in high oxygen tensions 1-2 days after plating but were better maintained in low, suggesting cells undergo a culture shock/stress after plating that is mitigated by reduced oxygen. In the presence of UM171, HSCs expanded significantly better at higher oxygen levels, but HPCs are better maintained in 5%O2. Ex vivo CD34+ expansions maintained under physiological O2 levels (1-14%O2) demonstrated significantly better/faster neutrophil recovery following transplantation compared to cells expanded at 21%O2 or input. Discussion HSCs/HPCs proliferate rapidly in high oxygen but have fewer quiescent cells, higher ROS, and are larger and more granular which are all characteristics associated with exhaustion. While high oxygen allows for faster growth, low tensions may mitigate cell stress and allow for prolonged growth (i.e., HSC/HPC expansion) while maintaining functional properties.

In Vivo Imaging of Lipid Droplets and Oxygen Status in Hepatic Tissues of Nonalcoholic Fatty Liver Model Mice Using a Lipophilic Ir(III) Complex

Nonalcoholic fatty liver disease (NAFLD) is becoming common worldwide. In pathophysiological studies of NAFLD, an in vivo optical probe that enables visualization of lipid droplets (LDs) and imaging of oxygen status in hepatic tissues simultaneously would be very useful. Here, we present the phosphorescent Ir(III) complex BTP ((btp)2Ir(acac) (btp = benzothienylpyridine, acac = acetylacetone)) as the first probe that meets this requirement. BTP was efficiently taken up into cultured 3T3-L1 adipocytes and selectively accumulated into LDs. Quantifying oxygen levels in LDs based on the phosphorescence lifetime of BTP allowed us to track changes in cellular oxygen tension after treatment with metabolic stimulants. Phosphorescence lifetime imaging microscopy combined with intravenously administered BTP in mice enabled specific visualization of LDs in hepatic lobules and simultaneous imaging of the oxygen gradient that decreased from the portal vein (PV) to the central vein (CV). NAFL model mice were created by feeding a high-fat diet (HFD) to mice for 3 or 7 days. The mice fed an HFD showed a marked increase in the amount and size of LDs in hepatocytes compared with those fed a normal diet, leading to abnormal microvascular structures. In addition, HFD-fed mice also exhibited reduced oxygen tension in areas other than the CV. Multicolor imaging with the LD-accumulated oxygen probe BTP and vasculature-staining FITC-lectin suggested that structural distortions of the sinusoidal microvasculature caused by enlarged LDs were associated with partial hypoxia in NAFL.

Association Between Changes in Norepinephrine Infusion Rate and Urinary Oxygen Tension After Cardiac Surgery

To determine if the administration of norepinephrine to patients recovering from on-pump cardiac surgery is associated with changes in urinary oxygen tension (PO2), an indirect index of renal medullary oxygenation. Single center, prospective observational study. Surgical intensive care unit (ICU). A nonconsecutive sample of 93 patients recovering from on-pump cardiac surgery. In the ICU, norepinephrine was the most commonly used vasopressor agent (90% of patients, 84/93), with fewer patients receiving epinephrine (48%, 45/93) or vasopressin (4%, 4/93). During the 30-to-60-minute period after increasing the infused dose of norepinephrine (n=89 instances), urinary PO2 decreased by (least squares mean ± SEM) 1.8 ± 0.5 mmHg from its baseline level of 25.1 ± 1.1 mmHg. Conversely, during the 30-to-60-minute period after the dose of norepinephrine was decreased (n=134 instances), urinary PO2 increased by 2.6 ± 0.5 mmHg from its baseline level of 22.7 ± 1.2 mmHg. No significant change in urinary PO2 was detected when the dose of epinephrine was decreased (n=21). There were insufficient observations to assess the effects of increasing the dose of epinephrine (n=11) or of changing the dose of vasopressin (n <4). In patients recovering from on-pump cardiac surgery, changes in norepinephrine dose are associated with reciprocal changes in urinary PO2, potentially reflecting an effect of norepinephrine on renal medullary oxygenation.

Enhancing bacterial cellulose production with hypoxia-inducible factors.

Komagataeibacter xylinus is an aerobic strain that produces bacterial cellulose (BC). Oxygen levels play a critical role in regulating BC synthesis in K. xylinus, and an increase in oxygen tension generally means a decrease in BC production. Fumarate nitrate reduction protein (FNR) and aerobic respiration control protein A (ArcA) are hypoxia-inducible factors, which can signal whether oxygen is present in the environment. In this study, FNR and ArcA were used to enhance the efficiency of oxygen signaling in K. xylinus, and globally regulate the transcription of the genome to cope with hypoxic conditions, with the goal of improving growth and BC production. FNR and ArcA were individually overexpressed in K. xylinus, and the engineered strains were cultivated under different oxygen tensions to explore how their overexpression affects cellular metabolism and regulation. Although FNR overexpression did not improve BC production, ArcA overexpression increased BC production by 24.0% and 37.5% as compared to the control under oxygen tensions of 15% and 40%, respectively. Transcriptome analysis showed that FNR and ArcA overexpression changed the way K. xylinus coped with oxygen tension changes, and that both FNR and ArcA overexpression enhanced the BC synthesis pathway. The results of this study provide a new perspective on the effect of oxygen signaling on growth and BC production in K. xylinus and suggest a promising strategy for enhancing BC production through metabolic engineering. KEY POINTS: • K. xylinus BC production increased after overexpression of ArcA • The young's modulus is enhanced by the ArcA overexpression • ArcA and FNR overexpression changed how cells coped with changes in oxygen tension.

Time Domains of Hypoxia Responses and -Omics Insights.

The ability to respond rapidly to changes in oxygen tension is critical for many forms of life. Challenges to oxygen homeostasis, specifically in the contexts of evolutionary biology and biomedicine, provide important insights into mechanisms of hypoxia adaptation and tolerance. Here we synthesize findings across varying time domains of hypoxia in terms of oxygen delivery, ranging from early animal to modern human evolution and examine the potential impacts of environmental and clinical challenges through emerging multi-omics approaches. We discuss how diverse animal species have adapted to hypoxic environments, how humans vary in their responses to hypoxia (i.e., in the context of high-altitude exposure, cardiopulmonary disease, and sleep apnea), and how findings from each of these fields inform the other and lead to promising new directions in basic and clinical hypoxia research.

Physioxia-induced downregulation of Tet2 in hematopoietic stem cells contributes to enhanced self-renewal

AbstractHematopoietic stem cells (HSCs) manifest impaired recovery and self-renewal with a concomitant increase in differentiation when exposed to ambient air as opposed to physioxia. Mechanism(s) behind this distinction are poorly understood but have the potential to improve stem cell transplantation. Single-cell RNA sequencing of HSCs in physioxia revealed upregulation of HSC self-renewal genes and downregulation of genes involved in inflammatory pathways and HSC differentiation. HSCs under physioxia also exhibited downregulation of the epigenetic modifier Tet2. Tet2 is α-ketoglutarate, iron- and oxygen-dependent dioxygenase that converts 5-methylcytosine to 5-hydroxymethylcytosine, thereby promoting active transcription. We evaluated whether loss of Tet2 affects the number and function of HSCs and hematopoietic progenitor cells (HPCs) under physioxia and ambient air. In contrast to wild-type HSCs (WT HSCs), a complete nonresponsiveness of Tet2−/− HSCs and HPCs to changes in oxygen tension was observed. Unlike WT HSCs, Tet2−/− HSCs and HPCs exhibited similar numbers and function in either physioxia or ambient air. The lack of response to changes in oxygen tension in Tet2−/− HSCs was associated with similar changes in self-renewal and quiescence genes among WT HSC-physioxia, Tet2−/− HSC-physioxia and Tet2−/− HSC-air. We define a novel molecular program involving Tet2 in regulating HSCs under physioxia.

CARDIAC ARRHYTHMIA AND HEMODYNAMIC EFFECTS DURING FIBEROPTIC BRONCHOSCOPY

Background: Arterial hypoxaemia is the commonest complication, since respiratory depressant drugs are used for premedication, and the airway is also partially occluded by the bronchoscope. The study is therefore designed to nd out the changes in arterial oxygen tension during FOB along with effect on central hemodynamics, electrocardiographically. Objectives: · To nd out the changes in arterial oxygen tension during FOB. · To study the effects of beroptic bronchoscopy on central hemodynamics, electrocardiographically. Methods: 100 patients aged 20 years and above undergoing FOB were evaluated for the arterial oxygen tension and cardiac rhythm changes at KNCH, Jodhpur. Results: All patients developed a fall in PaO2 following FOB which was highly signicant but hypoxaemia was noted only in 18 cases. There was a uniform rise in heart rate in all the patients after FOB which was statistically signicant. There was slight sinus tachycardia in most of the cases although E.C.G. indicated no major arrhythmias. There was no signicant change in pH level. Mean of SBP and mean of DBP was statistically signicant. Conclusion: All patients showed a decline in arterial PaO2 after FOB which was highly signicant. There was slight sinus tachycardia in most of cases. FOB itself does not endanger the patients with any signicant or serious complications.

PEAK EXPIRATORY FLOW RATE CHANGES AND HYPOXEMIA DURING FIBEROPTIC BRONCHOSCOPY

Background: Arterial hypoxaemia is the common complication, since respiratory depressant drugs are used for premedication, and the airway is also partially occluded by the bronchoscope. The study is therefore designed to nd out the changes in arterial oxygen tension and PEFR during FOB. Objectives: Ÿ To nd out the changes in arterial oxygen tension and in peak expiratory ow rate during FOB. Methods: 100 patients aged 20 years above undergoing FOB were evaluated for the arterial oxygen tension and peak expiratory ow rate changes at KNCH, Jodhpur. Results: All patients developed a fall in PaO2 following FOB but hypoxemia was noted only in 18 cases. The change in PEFR after FOB, no signicant statistical difference could be observed on statistically comparison. Conclusion: All patients showed a decline in arterial PaO2 after FOB which was highly signicant. FOB itself does not causes any signicant or serious complications.

HYPOXEMIA AND LUNG MECHANICS DURING FIBEROPTIC BRONCHOSCOPY

Background: Arterial hypoxaemia is the common complication, since respiratory depressant drugs are used for premedication, and the airway is also partially occluded by the bronchoscope. The study is therefore designed to nd out the changes in arterial oxygen tension and PFTduring FOB. Objectives: To nd out the changes in arterial oxygen tension and pulmonary function tests during FOB. Methods: One hundred patients aged 20 years above undergoing FOB were evaluated for the arterial oxygen tension and pulmonary function tests changes at KNCH, Jodhpur. Results: All patients developed a fall in PaO2 following FOB but hypoxemia was noted only in 18 cases. Bronchial washing, punch biopsy and brush biopsy did contribute to hypoxemia signicantly. The pulmonary functions which include change in V.C, FVC, FEV1 and PEFR after FOB, no statistical difference could be observed on statistically comparison. Conclusion: All patients showed a decline in arterial PaO2 after FOB which was highly signicant. FOB itself does not cause any signicant or serious complications.

Effects of Sodium Nitroprusside Administered Via a Subdural Intracranial Catheter on the Microcirculation, Oxygenation, and Electrocortical Activity of the Cerebral Cortex in a Pig Cardiac Arrest Model.

BackgroundPostischemic cerebral hypoperfusion has been indicated as an important contributing factor to secondary cerebral injury after cardiac arrest. We evaluated the effects of sodium nitroprusside administered via a subdural intracranial catheter on the microcirculation, oxygenation, and electrocortical activity of the cerebral cortex in the early postresuscitation period using a pig model of cardiac arrest.Methods and ResultsTwenty‐nine pigs were resuscitated with closed cardiopulmonary resuscitation after 14 minutes of untreated ventricular fibrillation. Thirty minutes after restoration of spontaneous circulation, 24 pigs randomly received either 4 mg of sodium nitroprusside (IT‐SNP group) or saline placebo (IT‐saline group) via subdural intracranial catheters and were observed for 5 hours. The same dose of sodium nitroprusside was administered intravenously in another 5 pigs. Compared with the IT‐saline group, the IT‐SNP group had larger areas under the curve for tissue oxygen tension and percent changes of arteriole diameter and number of perfused microvessels from baseline (all P<0.05) monitored on the cerebral cortex during the 5‐hour period, without severe hemodynamic instability. This group also showed faster recovery of electrocortical activity measured using amplitude‐integrated electroencephalography. Repeated‐measures analysis of variance revealed significant group–time interactions for these parameters. Intravenously administered sodium nitroprusside caused profound hypotension but did not appear to increase the cerebral parameters.ConclusionsSodium nitroprusside administered via a subdural intracranial catheter increased post–restoration of spontaneous circulation cerebral cortical microcirculation and oxygenation and hastened electrocortical activity recovery in a pig model of cardiac arrest. Further studies are required to determine its impact on the long‐term neurologic outcomes.

Nitric Oxide Production and Regulation in the Teleost Cardiovascular System.

Nitric Oxide (NO) is a free radical with numerous critical signaling roles in vertebrate physiology. Similar to mammals, in the teleost system the generation of sufficient amounts of NO is critical for the physiological function of the cardiovascular system. At the same time, NO amounts are strictly controlled and kept within basal levels to protect cells from NO toxicity. Changes in oxygen tension highly influence NO bioavailability and can modulate the mechanisms involved in maintaining the NO balance. While NO production and signaling appears to have general similarities with mammalian systems, the wide range of environmental adaptations made by fish, particularly with regards to differing oxygen availabilities in aquatic habitats, creates a foundation for a variety of in vivo models characterized by different implications of NO production and signaling. In this review, we present the biology of NO in the teleost cardiovascular system and summarize the mechanisms of NO production and signaling with a special emphasis on the role of globin proteins in NO metabolism.

Mobilising patients with severe acquired brain injury in intensive care (MAWERIC) – Protocol for a randomised cross-over trial

IntroductionIn the early phase after severe brain injury, patients are often bedridden in an attempt to control intracranial homeostasis; however, prolonged immobilisation may trigger complications. There is limited knowledge about the physiological effects of mobilisation in this early phase. ObjectiveTo investigate changes in brain tissue oxygen tension when patients are mobilised using a Sara Combilizer® in the early phase after severe brain injury, in a randomised cross-over design. MethodsPatients with traumatic brain injury, subarachnoid haemorrhage or intracranial haematoma, will be randomised to early mobilisation or rest (no mobilisation = control) on the first day that the patient is deemed to be fit for mobilisation, and the opposite on the next day. On both days, patients will undergo continuous multimodal monitoring measuring brain tissue oxygen tension (primary outcome), invasive blood pressure, heart rate, middle cerebral artery blood flow velocity by transcranial Doppler ultrasound, intracranial pressure, and microdialysis markers of cerebral oxidative metabolism. DiscussionIntensive care unit patients with acute brain injury are frequently immobilised in the early phase after the ictus. The optimal timing and intensity of mobilisation is unknown. The present study attempts to establish if early mobilisation is safe with respect to intracranial homeostasis.Protocol version 1.1.Date: 19.02.2022.Ethical registration: H-21002728; approved on August 11, 2021.GDPR registration: P-2021 − 105; approved on February 10, 2021.ClinicalTrials.govidentifier:NCT05038930; approved on September 8, 2021.Electronic case report file: REDCap-database; created on August 13, 2021.

An observational study to find out changes in arterial oxygen tension during fiberoptic bronchoscopy

Background: Arterial hypoxaemia is the commonest complication, since respiratory depressant drugs are used for premedication, and the airway is also partially occluded by the bronchoscope. The study is therefore designed to find out the changes in arterial oxygen tension during (FOB) along with effect on central hemodynamics, pre and post procedure ECG and PFT. Objectives were to find out the changes in arterial oxygen tension during FOB, to study the effects of FOB on central hemodynamics, electrocardiographically and pulmonary function tests.Methods: One hundred patients aged 20 years undergoing FOB were evaluated for the arterial oxygen tension and cardiac rhythm changes at KNCH, Jodhpur during 12 months study period from 2019 to 2020.Results: All patients developed a fall in PaO2 following FOB but hypoxaemia was noted only in 18 cases. Bronchial washing, punch biopsy and brush biopsy did contribute to hypoxaemia significantly. There was a uniform rise in heart rate in all the patients after FOB which was statistically significant. There was slight sinus tachycardia in most of the cases although ECG indicated no major arrhythmias. The pulmonary functions which include change in VC, FVC, FEV1 and PEFR after FOB, on statistically comparison no statistical difference could be observed. There was no significant change in PaCO2 level and pH level. Mean of SBP and mean of DBP was statistically significant.Conclusions: All patients showed a decline in arterial PaO2 after FOB which was highly significant. There was slight sinus tachycardia in most of cases. FOB itself does not endanger the patients with any significant or serious complications.