Journal articles on the topic 'Hyperoxia'
To see the other types of publications on this topic, follow the link: Hyperoxia.
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Hyperoxia.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Cucchiaro, Giovanni, Arthur H. Tatum, Michael C. Brown, Enrico M. Camporesi, John W. Daucher, and Tawfic S. Hakim. "Inducible nitric oxide synthase in the lung and exhaled nitric oxide after hyperoxia." American Journal of Physiology-Lung Cellular and Molecular Physiology 277, no. 3 (September 1, 1999): L636—L644. http://dx.doi.org/10.1152/ajplung.1999.277.3.l636.
Full textAbstract:
The effect of hyperoxia on nitric oxide (NO) production in intact animals is unknown. We described the effects of hyperoxia on inducible nitric oxide synthase (iNOS) expression and NO production in the lungs of rats exposed to high concentrations of oxygen. Animals were placed in sealed Plexiglas chambers and were exposed to either 85% oxygen (hyperoxic group) or 21% oxygen (negative control group). Animals were anesthetized after 24 and 72 h of exposure and were ventilated via a tracheotomy. We measured NO production in exhaled air (ENO) by chemiluminescence. The lungs were then harvested and processed for detection of iNOS by immunohistochemistry and Western blotting analysis. The same experiments were repeated in animals exposed to hyperoxia for 72 h after they were infused with l-arginine. We used rats that were injected intraperitoneally with Escherichia coli lipopolysaccharide to induce septic shock as a positive control group. Hyperoxia and septic shock induced expression of iNOS in the lung. However, ENO was elevated only in septic shock rats but was normal in the hyperoxic group. Exogenous infusion of l-arginine after hyperoxia did not increase ENO. To exclude the possibility that in the hyperoxic group NO was scavenged by oxygen radicals to form peroxynitrite, lungs were studied by immunohistochemistry for the detection of nitrotyrosine. Nitrotyrosine was found in septic shock animals but not in the hyperoxic group, further suggesting that NO is not synthesized in rats exposed to hyperoxia. We conclude that hyperoxia induces iNOS expression in the lung without an increase in NO concentration in the exhaled air.
2
Mak, Susanna, Zoltan Egri, Gemini Tanna, Rebecca Colman, and Gary E. Newton. "Vitamin C prevents hyperoxia-mediated vasoconstriction and impairment of endothelium-dependent vasodilation." American Journal of Physiology-Heart and Circulatory Physiology 282, no. 6 (June 1, 2002): H2414—H2421. http://dx.doi.org/10.1152/ajpheart.00947.2001.
Full textAbstract:
High arterial blood oxygen tension increases vascular resistance, possibly related to an interaction between reactive oxygen species and endothelium-derived vasoactive factors. Vitamin C is a potent antioxidant capable of reversing endothelial dysfunction due to increased oxidant stress. We tested the hypotheses that hyperoxic vasoconstriction would be prevented by vitamin C, and that acetylcholine-mediated vasodilation would be blunted by hyperoxia and restored by vitamin C. Venous occlusion strain gauge plethysmography was used to measure forearm blood flow (FBF) in 11 healthy subjects and 15 congestive heart failure (CHF) patients, a population characterized by endothelial dysfunction and oxidative stress. The effect of hyperoxia on FBF and derived forearm vascular resistance (FVR) at rest and in response to intra-arterial acetylcholine was recorded. In both healthy subjects and CHF patients, hyperoxia-mediated increases in basal FVR were prevented by the coinfusion of vitamin C. In healthy subjects, hyperoxia impaired the acetylcholine-mediated increase in FBF, an effect also prevented by vitamin C. In contrast, hyperoxia had no effect on verapamil-mediated increases in FBF. In CHF patients, hyperoxia did not affect FBF responses to acetylcholine or verapamil. The addition of vitamin C during hyperoxia augmented FBF responses to acetylcholine. These results suggest that hyperoxic vasoconstriction is mediated by oxidative stress. Moreover, hyperoxia impairs acetylcholine-mediated vasodilation in the setting of intact endothelial function. These effects of hyperoxia are prevented by vitamin C, providing evidence that hyperoxia-derived free radicals impair the activity of endothelium-derived vasoactive factors.
3
Yao, Qin, Musa A. Haxhiu, Syed I. Zaidi, Shijian Liu, Anjum Jafri, and Richard J. Martin. "Hyperoxia enhances brain-derived neurotrophic factor and tyrosine kinase B receptor expression in peribronchial smooth muscle of neonatal rats." American Journal of Physiology-Lung Cellular and Molecular Physiology 289, no. 2 (August 2005): L307—L314. http://dx.doi.org/10.1152/ajplung.00030.2005.
Full textAbstract:
Airway hyperreactivity is one of the hallmarks of hyperoxic lung injury in early life. As neurotrophins such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are potent mediators of neuronal plasticity, we hypothesized that neurotrophin levels in the pulmonary system may be disturbed by hyperoxic exposure. We therefore evaluated the effects of hyperoxia on the expression of BDNF, NGF, and their corresponding high-affinity receptors, TrkB and TrkA, respectively, in the lung of rat pups. Five-day-old Sprague-Dawley rat pups were randomized to hyperoxic or control groups and then continuously exposed to hyperoxia (>95% oxygen) or normoxia over 7 days. At both mRNA and protein levels, BDNF was detected in lung but not in trachea; its level was substantially enhanced in lungs from the hyperoxia-exposed rat pups. Distribution of BDNF mRNA by in situ hybridization indicates that peribronchial smooth muscle was the major source of increased BDNF production in response to hyperoxic exposure. Interestingly, hyperoxia-induced elevation of BDNF was not accompanied by any changes of NGF levels in lung. Furthermore, hyperoxic exposure increased the expression of TrkB in peribronchial smooth muscle but had no effect on the distribution of the specific NGF receptor TrkA. These findings indicate that hyperoxic stress not only upregulates BDNF at mRNA and protein levels but also enhances TrkB within peribronchial smooth muscle. However, there was no corresponding effect on NGF and TrkA receptors. We speculate that the increased level of BDNF may contribute to hyperoxia-induced airway hyperresponsiveness in early postnatal life.
4
Buckley, S., W. Shi, L. Barsky, and D. Warburton. "TGF-β signaling promotes survival and repair in rat alveolar epithelial type 2 cells during recovery after hyperoxic injury." American Journal of Physiology-Lung Cellular and Molecular Physiology 294, no. 4 (April 2008): L739—L748. http://dx.doi.org/10.1152/ajplung.00294.2007.
Full textAbstract:
Hyperoxic rats treated with inosine during oxygen exposure have increased levels of active transforming growth factor (TGF)-β in the bronchoalveolar lavage (BAL), yet alveolar epithelial type 2 cells (AEC2) isolated from these animals demonstrate less hyperoxia-induced DNA damage and increased expression of active Smad2. To determine whether TGF-β1 signaling per se protected AEC2 against hyperoxic damage, freshly isolated AEC2 from hyperoxic rats were incubated with TGF-β1 for 24 h and assayed for DNA damage by fluorescein-activated cell sorter analysis of TdT-mediated dUTP nick end labeling. TGF-β1 was protective over a concentration range similar to that in BAL of inosine-treated hyperoxic animals (50–5,000 pg/ml). TGF-β1 also augmented hyperoxia-induced DNA repair activity and cell migration, stimulated autocrine secretion of fibronectin, accelerated closure of a monolayer scratch wound, and restored hyperoxia-depleted VEGF secretion by AEC2 to normoxic levels. The TGF-β receptor type I activin-like kinase-4, -5, and -7 inhibitor peptide SB-505124 abolished the protective effect of TGF-β on hyperoxic DNA damage and increased TdT-mediated dUTP nick end labeling in normoxic cells. These data suggest that endogenous TGF-β-mediated Smad signaling is required for AEC2 homeostasis in vitro, while exogenous TGF-β1 treatment of hyperoxia-damaged AEC2 results in a cell that is equipped to survive, repair, migrate, secrete matrix, and induce new blood vessel formation more efficiently than AEC2 primed by hyperoxia alone.
5
Dean, Jay B., Daniel K. Mulkey, Richard A. Henderson, Stephanie J. Potter, and Robert W. Putnam. "Hyperoxia, reactive oxygen species, and hyperventilation: oxygen sensitivity of brain stem neurons." Journal of Applied Physiology 96, no. 2 (February 2004): 784–91. http://dx.doi.org/10.1152/japplphysiol.00892.2003.
Full textAbstract:
Hyperoxia is a popular model of oxidative stress. However, hyperoxic gas mixtures are routinely used for chemical denervation of peripheral O2 receptors in in vivo studies of respiratory control. The underlying assumption whenever using hyperoxia is that there are no direct effects of molecular O2 and reactive O2 species (ROS) on brain stem function. In addition, control superfusates used routinely for in vitro studies of neurons in brain slices are, in fact, hyperoxic. Again, the assumption is that there are no direct effects of O2 and ROS on neuronal activity. Research contradicts this assumption by demonstrating that O2 has central effects on the brain stem respiratory centers and several effects on neurons in respiratory control areas; these need to be considered whenever hyperoxia is used. This mini-review summarizes the long-recognized, but seldom acknowledged, paradox of respiratory control known as hyperoxic hyperventilation. Several proposed mechanisms are discussed, including the recent hypothesis that hyperoxic hyperventilation is initiated by increased production of ROS during hyperoxia, which directly stimulates central CO2 chemoreceptors in the solitary complex. Hyperoxic hyperventilation may provide clues into the fundamental role of redox signaling and ROS in central control of breathing; moreover, oxidative stress may play a role in respiratory control dysfunction. The practical implications of brain stem O2 and ROS sensitivity are also considered relative to the present uses of hyperoxia in respiratory control research in humans, animals, and brain stem tissues. Recommendations for future research are also proposed.
6
Sadek, A., R. Khattab, A. Amer, and A. Youssef. "Protective role of caffeine versus N-acetylcysteine in hyperoxic acute lung injury in neonatal rats." Journal of Morphological Sciences 34, no. 02 (April 2017): 058–67. http://dx.doi.org/10.4322/jms.113617.
Full textAbstract:
Abstract Introduction: Prolonged breathing of high oxygen concentration leads to hyperoxic acute lung injury. Neonatal Respiratory diseases usually require increased supplement of high oxygen concentrations, so neonates are more susceptible to hyperoxic acute lung injury. The aim of this work was to investigate the protective role of caffeine versus N-acetylcysteine against hyperoxic acute lung injury in neonatal rats. Materials and Methods: 32 albino rats aged seven days were used in this experiment. The pups were divided into four groups; 1) Control or normoxic group; rats placed in normoxic chamber where fraction of inspired oxygen (FiO2) was 0.21, 2) Hyperoxic group; rats were placed in hyperoxic chamber (FiO2>0.8) using an oxygen flow of 1.5 Litre/min, 3) Hyperoxia-CAF group; rats exposed to hyperoxia and received a single intra-peritoneal injection of 20 mg/kg caffeine just prior to exposure, and 4) Hyperoxia-NAC group; rats exposed to hyperoxia and received a single intra-peritoneal injection of 150 mg/kg N-acetylcysteine just prior to exposure. 48 hours after exposure, lung specimens were processed for histological and immunohistochemical study using caspase-3, cluster of differentiation-68-antibody (CD68) and interleukin-1-beta (IL-1β). Results: Neonatal hyperoxia led to severe impairment in lung architecture, with a highly significant increase in alveolar macrophages. Also, caspase and IL-1β immune-reaction were increased significantly as compared to control group. Caffeine could improve the histolopathological picture of hyperoxic acute lung injury, and also could decrease alveolar macrophage count and IL-1β immune-reaction better than N-acetylcysteine. Conclusion: Caffeine is more effective than N-acetylcysteine in prophylaxis against hyperoxic acute lung injury in neonates.
7
Xu, Dong, Jill R. Guthrie, Sherry Mabry, Thomas M. Sack, and William E. Truog. "Mitochondrial aldehyde dehydrogenase attenuates hyperoxia-induced cell death through activation of ERK/MAPK and PI3K-Akt pathways in lung epithelial cells." American Journal of Physiology-Lung Cellular and Molecular Physiology 291, no. 5 (November 2006): L966—L975. http://dx.doi.org/10.1152/ajplung.00045.2006.
Full textAbstract:
Oxygen toxicity is one of the major risk factors in the development of the chronic lung disease or bronchopulmonary dysplasia in premature infants. Using proteomic analysis, we discovered that mitochondrial aldehyde dehydrogenase (mtALDH or ALDH2) was downregulated in neonatal rat lung after hyperoxic exposure. To study the role of mtALDH in hyperoxic lung injury, we overexpressed mtALDH in human lung epithelial cells (A549) and found that mtALDH significantly reduced hyperoxia-induced cell death. Compared with control cells (Neo-A549), the necrotic cell death in mtALDH-overexpressing cells (mtALDH-A549) decreased from 25.3 to 6.5%, 50.5 to 9.1%, and 52.4 to 15.1% after 24-, 48-, and 72-h hyperoxic exposure, respectively. The levels of intracellular and mitochondria-derived reactive oxygen species (ROS) in mtALDH-A549 cells after hyperoxic exposure were significantly lowered compared with Neo-A549 cells. mtALDH overexpression significantly stimulated extracellular signal-regulated kinase (ERK) phosphorylation under normoxic and hyperoxic conditions. Inhibition of ERK phosphorylation partially eliminated the protective effect of mtALDH in hyperoxia-induced cell death, suggesting ERK activation by mtALDH conferred cellular resistance to hyperoxia. mtALDH overexpression augmented Akt phosphorylation and maintained the total Akt level in mtALDH-A549 cells under normoxic and hyperoxic conditions. Inhibition of phosphatidylinositol 3-kinase (PI3K) activation by LY294002 in mtALDH-A549 cells significantly increased necrotic cell death after hyperoxic exposure, indicating that PI3K-Akt activation by mtALDH played an important role in cell survival after hyperoxia. Taken together, these data demonstrate that mtALDH overexpression attenuates hyperoxia-induced cell death in lung epithelial cells through reduction of ROS, activation of ERK/MAPK, and PI3K-Akt cell survival signaling pathways.
8
Patel, Vivek, Katelyn Dial, Jiaqi Wu, Alex G. Gauthier, Wenjun Wu, Mosi Lin, Michael G. Espey, Douglas D. Thomas, Charles R. Ashby, and Lin L. Mantell. "Dietary Antioxidants Significantly Attenuate Hyperoxia-Induced Acute Inflammatory Lung Injury by Enhancing Macrophage Function via Reducing the Accumulation of Airway HMGB1." International Journal of Molecular Sciences 21, no. 3 (February 1, 2020): 977. http://dx.doi.org/10.3390/ijms21030977.
Full textAbstract:
Mechanical ventilation with hyperoxia is the major supportive measure to treat patients with acute lung injury and acute respiratory distress syndrome (ARDS). However, prolonged exposure to hyperoxia can induce oxidative inflammatory lung injury. Previously, we have shown that high levels of airway high-mobility group box 1 protein (HMGB1) mediate hyperoxia-induced acute lung injury (HALI). Using both ascorbic acid (AA, also known as vitamin C) and sulforaphane (SFN), an inducer of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), we tested the hypothesis that dietary antioxidants can mitigate HALI by ameliorating HMGB1-compromised macrophage function in phagocytosis by attenuating hyperoxia-induced extracellular HMGB1 accumulation. Our results indicated that SFN, which has been shown to attenute HALI in mice exposed to hyperoxia, dose-dependently restored hyperoxia-compromised macrophage function in phagocytosis (75.9 ± 3.5% in 0.33 µM SFN versus 50.7 ± 1.8% in dimethyl sulfoxide (DMSO) control, p < 0.05) by reducing oxidative stress and HMGB1 release from cultured macrophages (47.7 ± 14.7% in 0.33 µM SFN versus 93.1 ± 14.6% in DMSO control, p < 0.05). Previously, we have shown that AA enhances hyperoxic macrophage functions by reducing hyperoxia-induced HMGB1 release. Using a mouse model of HALI, we determined the effects of AA on hyperoxia-induced inflammatory lung injury. The i.p. administration of 50 mg/kg of AA to mice exposed to 72 h of ≥98% O2 significantly decreased hyperoxia-induced oxidative and nitrosative stress in mouse lungs. There was a significant decrease in the levels of airway HMGB1 (43.3 ± 12.2% in 50 mg/kg AA versus 96.7 ± 9.39% in hyperoxic control, p < 0.05), leukocyte infiltration (60.39 ± 4.137% leukocytes numbers in 50 mg/kg AA versus 100 ± 5.82% in hyperoxic control, p < 0.05) and improved lung integrity in mice treated with AA. Our study is the first to report that the dietary antioxidants, ascorbic acid and sulforaphane, ameliorate HALI and attenuate hyperoxia-induced macrophage dysfunction through an HMGB1-mediated pathway. Thus, dietary antioxidants could be used as potential treatments for oxidative-stress-induced acute inflammatory lung injury in patients receiving mechanical ventilation.
9
Houssière, Anne, Boutaina Najem, Nicolas Cuylits, Sophie Cuypers, Robert Naeije, and Philippe van de Borne. "Hyperoxia enhances metaboreflex sensitivity during static exercise in humans." American Journal of Physiology-Heart and Circulatory Physiology 291, no. 1 (July 2006): H210—H215. http://dx.doi.org/10.1152/ajpheart.01168.2005.
Full textAbstract:
Peripheral chemoreflex inhibition with hyperoxia decreases sympathetic nerve traffic to muscle circulation [muscle sympathetic nerve activity (MSNA)]. Hyperoxia also decreases lactate production during exercise. However, hyperoxia markedly increases the activation of sensory endings in skeletal muscle in animal studies. We tested the hypothesis that hyperoxia increases the MSNA and mean blood pressure (MBP) responses to isometric exercise. The effects of breathing 21% and 100% oxygen at rest and during isometric handgrip at 30% of maximal voluntary contraction on MSNA, heart rate (HR), MBP, blood lactate (BL), and arterial O2 saturation (SaO2) were determined in 12 healthy men. The isometric handgrips were followed by 3 min of postexercise circulatory arrest (PE-CA) to allow metaboreflex activation in the absence of other reflex mechanisms. Hyperoxia lowered resting MSNA, HR, MBP, and BL but increased SaO2 compared with normoxia (all P < 0.05). MSNA and MBP increased more when exercise was performed in hyperoxia than in normoxia (MSNA: hyperoxic exercise, 255 ± 100% vs. normoxic exercise, 211 ± 80%, P = 0.04; and MBP: hyperoxic exercise, 33 ± 9 mmHg vs. normoxic exercise, 26 ± 10 mmHg, P = 0.03). During PE-CA, MSNA and MBP remained elevated (both P < 0.05) and to a larger extent during hyperoxia than normoxia ( P < 0.05). Hyperoxia enhances the sympathetic and blood pressure (BP) reactivity to metaboreflex activation. This is due to an increase in metaboreflex sensitivity by hyperoxia that overrules the sympathoinhibitory and BP lowering effects of chemoreflex inhibition. This occurs despite a reduced lactic acid production.
10
Schauer, Steven G., Michael D. April, Jason F. Naylor, Nee-Kofi Mould-Millman, Vikhyat S. Bebarta, Tyson E. Becker, Joseph K. Maddry, and Adit A. Ginde. "Incidence of Hyperoxia in Combat Wounded in Iraq and Afghanistan: A Potential Opportunity for Oxygen Conservation." Military Medicine 184, no. 11-12 (May 29, 2019): 661–67. http://dx.doi.org/10.1093/milmed/usz125.
Full textAbstract:
Abstract Introduction Oxygen supplementation is frequently used in critically injured trauma casualties in the combat setting. Oxygen supplies in the deployed setting are limited so excessive use of oxygen may unnecessarily consume this limited resource. We describe the incidence of supraphysiologic oxygenation (hyperoxia) within casualties in the Department of Defense Trauma Registry (DoDTR). Methods This is a subanalysis of previously published data from the DoDTR – we isolated casualties with a documented arterial blood gas (ABG) and categorized hyperoxia as an arterial oxygen >100 mmHg and extreme hyperoxia > 300 mmHg (a subset of hyperoxia). We defined serious injuries as those with an Abbreviated Injury Score (AIS) of 3 or greater. We defined a probable moderate traumatic brain injury of those with an AIS of 3 or greater for the head region and at least one Glasgow Coma Scale at 8 or less. Results Our initial search yielded 28,222 casualties, of which 10,969 had at least one ABG available. Within the 10,969, the proportion of casualties experiencing hyperoxia in this population was 20.6% (2,269) with a subset of 4.1% (452) meeting criteria for extreme hyperoxia. Among those with hyperoxia, the median age was 25 years (IQR 21–30), most were male (96.8%), most frequently US forces (41.4%), injured in Afghanistan (68.3%), injured by explosive (61.1%), with moderate injury scores (median 17, IQR 10–26), and most (93.8%) survived to hospital discharge. A total of 17.8% (1,954) of the casualties underwent endotracheal intubation: 27.5% (538 of 1,954) prior to emergency department (ED) arrival and 72.5% (1,416 of 1,954) within the ED. Among those intubated in the prehospital setting, upon ED arrival 35.1% (189) were hyperoxic, and a subset of 5.6% (30) that were extremely hyperoxic. Among those intubated in the ED, 35.4% (502) were hyperoxic, 7.9% (112) were extremely hyperoxic. Within the 1,277 with a probable TBI, 44.2% (565) experienced hyperoxia and 9.5% (122) met criteria for extreme hyperoxia. Conclusions In our dataset, more than 1 in 5 casualties overall had documented hyperoxia on ABG measurement, 1 in 3 intubated casualties, and almost 1 in 2 TBI casualties. With limited oxygen supplies in theater and logistical challenges with oxygen resupply, efforts to avoid unnecessary oxygen supplementation may have material impact on preserving this scarce resource and avoid potential detrimental clinical effects from supraphysiologic oxygen concentrations.
11
Petrache, Irina, Mary E. Choi, Leo E. Otterbein, Beek Yoke Chin, Lin L. Mantell, Stuart Horowitz, and Augustine M. K. Choi. "Mitogen-activated protein kinase pathway mediates hyperoxia-induced apoptosis in cultured macrophage cells." American Journal of Physiology-Lung Cellular and Molecular Physiology 277, no. 3 (September 1, 1999): L589—L595. http://dx.doi.org/10.1152/ajplung.1999.277.3.l589.
Full textAbstract:
We have previously demonstrated that the lungs of mice can exhibit increased programmed cell death or apoptosis after hyperoxic exposure in vivo. In this report, we show that hyperoxic exposure in vitro can also induce apoptosis in cultured murine macrophage cells (RAW 264.7) as assessed by DNA-laddering, terminal deoxynucleotidyltransferase dUTP nick end-labeling, and nucleosomal assays. To further delineate the signaling pathway of hyperoxia-induced apoptosis in RAW 264.7 macrophages, we first show that hyperoxia can activate the mitogen-activated protein kinase (MAPK) pathway, the extracellular signal-regulated kinases (ERKs) p42/p44, in a time-dependent manner as assessed by increased phosphorylation of ERK1/ERK2 by Western blot analyses. Neither the c-Jun NH2-terminal kinase/stress-activated protein kinase nor the p38 MAPK was activated by hyperoxia in these cells. Chemical or genetic inhibition of the ERK p42/p44 MAPK pathway by PD-98059, a selective inhibitor of MAPK kinase, and dominant negative mutants of ERK, respectively, attenuated hyperoxia-induced apoptosis as assessed by DNA laddering and nucleosomal ELISAs. Taken together, our data suggest that hyperoxia can induce apoptosis in cultured murine macrophages and that the MAPK pathway mediates hyperoxia-induced apoptosis.
12
Yamada, Mitsuhiro, Hiroshi Kubo, Seiichi Kobayashi, Kota Ishizawa, and Hidetada Sasaki. "Interferon-γ: a key contributor to hyperoxia-induced lung injury in mice." American Journal of Physiology-Lung Cellular and Molecular Physiology 287, no. 5 (November 2004): L1042—L1047. http://dx.doi.org/10.1152/ajplung.00155.2004.
Full textAbstract:
Hyperoxia-induced lung injury complicates the care of many critically ill patients who receive supplemental oxygen therapy. Hyperoxic injury to lung tissues is mediated by reactive oxygen species, inflammatory cell activation, and release of cytotoxic cytokines. IFN-γ is known to be induced in lungs exposed to high concentrations of oxygen; however, its contribution to hyperoxia-induced lung injury remains unclear. To determine whether IFN-γ contributes to hyperoxia-induced lung injury, we first used anti-mouse IFN-γ antibody to blockade IFN-γ activity. Administration of anti-mouse IFN-γ antibody inhibited hyperoxia-induced increases in pulmonary alveolar permeability and neutrophil migration into lung air spaces. To confirm that IFN-γ contributes to hyperoxic lung injury, we then simultaneously exposed IFN-γ-deficient (IFN-γ−/−) mice and wild-type mice to hyperoxia. In the early phase of hyperoxia, permeability changes and neutrophil migration were significantly reduced in IFN-γ−/− mice compared with wild-type mice, although the differences in permeability changes and neutrophil migration between IFN-γ−/− mice and wild-type mice were not significant in the late phase of hyperoxia. The concentrations of IL-12 and IL-18, two cytokines that play a role in IFN-γ induction, significantly increased in bronchoalveolar lavage fluid after exposure to hyperoxia in both IFN-γ−/− mice and wild-type mice, suggesting that hyperoxia initiates upstream events that result in IFN-γ production. Although there was no significant difference in overall survival, IFN-γ−/− mice had a better early survival rate than did the wild-type mice. Therefore, these data strongly suggest that IFN-γ is a key molecular contributor to hyperoxia-induced lung injury.
13
Chen, Yin, Dong Wei, Jin Zhao, Xiangnan Xu, and Jingyu Chen. "Reduction of hyperoxic acute lung injury in mice by Formononetin." PLOS ONE 16, no. 1 (January 7, 2021): e0245050. http://dx.doi.org/10.1371/journal.pone.0245050.
Full textAbstract:
Background The antioxidant and anti-inflammatory features of Formononetin, an isoflavone constituent extracted from traditional Chinese medicine, have been reported. The present study investigated that whether Formononetin plays a benefit on hyperoxic ALI. Methods C57BL/6 mice were exposed to hyperoxia for 72 h to produce experimental hyperoxic ALI model. Formononetin or vehicle was administrated intraperitoneally. Samples from the lung were collected at 72 h post hyperoxia exposure for further study. Pulmonary microvascular endothelial cells isolated from the lung of C57BL/6 mice were used for in vitro study. Results Formononetin pretreatment notably attenuated hyperoxia-induced elevating pulmonary water content, upregulation of proinflammatory cytokine levels and increasing infiltration of neutrophil in the lung. Western blot analyses showed that Formononetin enhanced the expression of nuclear factor erythroid-2-related factor 2 (Nrf2) which is a key transcription factor regulating the expression of heme oxygenase-1 (HO-1). Formononetin increased HO-1 expression and activity compared with vehicle-treated animals. Moreover, Formononetin reversed hyperoxia-caused the reduction of M2 macrophage polarization. However, pretreatment of a HO-1 inhibitor reduced the protective effect of Formononetin on hyperoxic ALI. Cell study showed that the Formononetin-induced upregulation of HO-1 was abolished when the Nrf2 was silenced. Conclusions Formononetin pretreatment reduces hyperoxia-induced ALI via Nrf2/HO-1-mediated antioxidant and anti-inflammatory effects.
14
Agani, F. H., N. T. Kuo, C. H. Chang, I. A. Dreshaj, C. F. Farver, J. E. Krause, P. Ernsberger, M. A. Haxhiu, and R. J. Martin. "Effect of hyperoxia on substance P expression and airway reactivity in the developing lung." American Journal of Physiology-Lung Cellular and Molecular Physiology 273, no. 1 (July 1, 1997): L40—L45. http://dx.doi.org/10.1152/ajplung.1997.273.1.l40.
Full textAbstract:
This study was undertaken to characterize changes in the tachykinin system induced by hyperoxic exposure and the potential effects on airway contractile responses. We exposed 7-day-old rat pups to either room air or hyperoxia (> 95% O2) for 7 days to assess pulmonary beta-preprotachykinin (beta-PPT) gene expression, substance P (SP) levels, and airway contractile responses to cholinergic stimulation before and after neurokinin-1 (NK1) receptor blockade. Lung beta-PPT mRNA expression, lung and tracheal SP levels, and contractile responses to exogenous acetylcholine and electrical field stimulation were measured in vitro in normoxia- and hyperoxia-exposed tracheal cylinders. Hyperoxia caused a 1.1- to 2.6-fold increase in steady-state lung beta-PPT mRNA and a 50 and 32% increase in SP levels of lung and trachea, respectively. In response to cholinergic stimulation, maximal contractile force (Emax) of hyperoxia exposed tracheal muscle was significantly higher than for normoxic controls. Addition of the SP (NK1) receptor blocker CP-99994 (10 microM) decreased sensitivity to electrical field stimulation in both hyperoxic and normoxic trachea without a significant decline in Emax. These data provide evidence for both increased SP production and enhanced maximal contractile responses of hyperoxia-exposed neonatal trachea to cholinergic stimulation. The tachykinin peptide SP does not, however, appear to play a major role in the enhanced airway reactivity associated with hyperoxic lung injury during early postnatal life.
15
Pala Cifci, Seyhan, Yasemin Urcan Tapan, Bengu Turemis Erkul, Yusuf Savran, and Bilgin Comert. "The Impact of Hyperoxia on Outcome of Patients Treated with Noninvasive Respiratory Support." Canadian Respiratory Journal 2020 (May 6, 2020): 1–6. http://dx.doi.org/10.1155/2020/3953280.
Full textAbstract:
Objective. Oxygen therapy is one of the most common treatment modalities for hypoxemic patients, but target goals for normoxemia are not clearly defined. Therefore, iatrogenic hyperoxia is a very common situation. The results from the recent clinical researches about hyperoxia indicate that hyperoxia can be related to worse outcomes than expected in some critically ill patients. According to our literature knowledge, there are not any reports researching the effect of hyperoxia on clinical course of patients who are not treated with invasive mechanical ventilation. In this study, we aimed to determine the effect of hyperoxia on mortality, and length of stay and also possible side effects of hyperoxia on the patients who are treated with oxygen by noninvasive devices. Materials and Methods. One hundred and eighty-seven patients who met inclusion criteria, treated in Dokuz Eylul University Medical Intensive Care Unit between January 1, 2016, and October 31, 2018, were examined retrospectively. These patients’ demographic data, oxygen saturation (SpO2) values for the first 24 hours, APACHE II (Acute Physiology and Chronic Health Evaluation II) scores, whether they needed intubation, if they did how many days they got ventilated, length of stay in intensive care unit and hospital, maximum PaO2 values of the first day, oxygen treatment method of the first 24 hours, and the rates of mortality were recorded. Results. Hyperoxemia was determined in 62 of 187 patients who were not treated with invasive mechanic ventilation in the first 24 hours of admission. Upon further investigation of the relation between comorbid situations and hyperoxia, hyperoxia frequency in patients with COPD was detected to be statistically low (16% vs. 35%, p<0.008). Hospital mortality was significantly high (51.6% vs. 35.2%, p<0.04) in patients with hyperoxia. When the types of oxygen support therapies were investigated, hyperoxia frequency was found higher in patients treated with supplemental oxygen (nasal cannula, oronasal mask, high flow oxygen therapy) than patients treated with NIMV (44.2% vs. 25.5%, p<0.008). After exclusion of 56 patients who were intubated and treated with invasive mechanical ventilation after the first 24 hours, hyperoxemia was determined in 46 of 131 patients. Mortality in patients with hyperoxemia who were not treated with invasive mechanical ventilation during hospital stay was statistically higher when compared to normoxemic patients (41.3% vs 15.3%, p<0.001). Conclusion. We report that hyperoxemia increases the hospital mortality in patients treated with noninvasive respiratory support. At the same time, we determined that hyperoxemia frequency was lower in COPD patients and the ones treated with NIMV. Conservative oxygen therapy strategy can be suggested to decrease the hyperoxia prevalence and mortality rates.
16
Kim, Sei Won, In Kyoung Kim, Jick Hwan Ha, Chang Dong Yeo, Hyeon Hui Kang, Jin Woo Kim, and Sang Haak Lee. "Normobaric hyperoxia inhibits the progression of lung cancer by inducing apoptosis." Experimental Biology and Medicine 243, no. 9 (May 2018): 739–48. http://dx.doi.org/10.1177/1535370218774737.
Full textAbstract:
Hypoxia is a critical characteristic of solid tumors with respect to cancer cell survival, angiogenesis, and metastasis. Hyperoxic treatment has been attempted to reverse hypoxia by enhancing the amount of dissolved oxygen in the plasma. In this study, we evaluated the effects of normobaric hyperoxia on the progression of lung cancer to determine whether oxygen toxicity can be used in cancer therapy. Following a tail vein injection of the Lewis lung carcinoma cells, C57BL/6J mice were exposed to a 24-h normobaric hyperoxia/normoxia cycle for two weeks. In addition, A549 lung cancer cells were incubated in a normobaric hyperoxia chamber for a 24-h period. As a result, the size and number of tumors in the lung decreased significantly with exposure to normobaric hyperoxia in the mouse model. Cell viability, colony-forming ability, migration, and invasion all decreased significantly in A549 cells exposed to normobaric hyperoxia and the normal control group exposed to normobaric hyperoxia showed no significant damage. Oxidative stress was more prominent with exposure to normobaric hyperoxia in cancer cells. A549 cells exposed to normobaric hyperoxia showed a significantly higher cell apoptosis ratio compared with A549 cells without normobaric hyperoxia exposure and normal human lung cells (BEAS-2B cells). The Bax/Bcl-2 mRNA expression ratio also increased significantly. Changes in the key regulators of apoptosis were similar between in vivo and in vitro conditions. The p-ERK level decreased, while the p-JNK level increased, after normobaric hyperoxia exposure in A549 cells. This study demonstrated the role of normobaric hyperoxia in inhibiting lung cancer. Normal tissue and cells showed no significant hyperoxic damage in our experimental setting. The anti-tumor effect of normobaric hyperoxia may due to the increased reactive oxygen species activity and apoptosis, which is related to the mitogen-activated protein kinase pathway. Impact statement Normobaric hyperoxia (NBO) is a feasible therapy for cancer with a low complication rate. Although NBO may be beneficial in cancer treatment, very few studies have been conducted; thus, the evidence is thin. This is the first study to clearly demonstrate morphological changes in lung cancer with NBO exposure and to investigate the underlying mechanisms both in vivo and in vitro. This study will arouse interest in NBO treatment and promote further research.
17
Thiruvenkataramani, Ranga Prasanth, Amal Abdul-Hafez, Ira Gewolb, and Bruce Uhal. "Mas Receptor Agonist AVE0991 increases surfactant protein expression under hyperoxic conditions in human lung epithelial cells." Journal of Lung, Pulmonary & Respiratory Research 7, no. 4 (November 17, 2020): 85–91. http://dx.doi.org/10.15406/jlprr.2020.07.00235.
Full textAbstract:
Background: Hyperoxia in pre-term neonates is a known risk factor of bronchopulmonary dysplasia (BPD). Hyperoxia is known to cause oxidative stress, inflammatory changes that leads to surfactant deactivation, and decreased surfactant expression. The previous research has shown short term exposure to hyperoxia increases surfactant protein expression but decreased expression in long term exposure. Local tissue renin-angiotensin system (RAS) is associated with tissue injury and repair and it may play a role in BPD. Endogenous peptide angiotensin 1-7 acts on the MAS receptor. The activation of the MAS receptor was previously shown to have protective pulmonary responses. However, the effect of MAS receptor activation on surfactant proteins in hyperoxic conditions has not been tested. Objective: To determine the effects of hyperoxia with or without MAS receptor activation on Surfactant proteins. Methods: Human epithelial cell line A549 and human primary alveolar epithelial cells (AECs) were cultured to sub-confluence (60-75%) and treated with hyperoxia (95% oxygen) and normoxia (21% oxygen) for 72 hours with or without the MAS receptor agonist (AVE0991) in serum-free F-12 nutrient media. Cells were lysed and cell lysates were collected for western blot. The statistical analysis was done using Student-Newman-Keuls Multiple comparison test. Results: Surfactant protein concentration increased in AVE treated group under the hyperoxic condition when compared to the control group in both A549 cells and human primary AECs. Surfactant protein was in higher concentration in AVE0991 treated cells in both hyperoxic and normoxic conditions when compared to the non-treated control group. Conclusions: MAS receptor activation via AVE0991 causes an increase in Surfactant protein concentration in both hyperoxic and normoxic conditions. As per our experiments, hyperoxic conditions decrease the production of surfactant protein when compared to normoxic conditions. These results may reveal a novel potential drug for BPD treatment and decrease its severity.
18
Sutherland, Megan R., Megan O'Reilly, Kelly Kenna, Kimberley Ong, Richard Harding, Foula Sozo, and M. Jane Black. "Neonatal hyperoxia: effects on nephrogenesis and long-term glomerular structure." American Journal of Physiology-Renal Physiology 304, no. 10 (May 15, 2013): F1308—F1316. http://dx.doi.org/10.1152/ajprenal.00172.2012.
Full textAbstract:
Preterm neonates are born while nephrogenesis is ongoing and are commonly exposed to factors in the extrauterine environment that may impair renal development. Supplemental oxygen therapy exposes the preterm infant to a hyperoxic environment that may induce oxidative stress. Our aim was to determine the immediate and long-term effects of exposure to hyperoxia, during the period of postnatal nephrogenesis, on renal development. Newborn mice (C57BL/6J) were kept in a normoxic (room air, 21% oxygen) or a controlled hyperoxic (65% oxygen) environment from birth to postnatal day 7 ( P7d). From P7d, animals were maintained in room air until early adulthood at postnatal day 56 ( P56d) or middle age (10 mo; P10mo). Pups were assessed for glomerular maturity and renal corpuscle cross-sectional area at P7d (control n = 14; hyperoxic n = 14). Nephron number and renal corpuscle size were determined stereologically at P56d (control n = 14; hyperoxic n = 14) and P10mo (control n = 10; hyperoxic n = 10). At P7d, there was no effect of hyperoxia on glomerular size or maturity. In early adulthood ( P56d), body weights, relative kidney weights and volumes, and nephron number were not different between groups, but the renal corpuscles were significantly enlarged. This was no longer evident at P10mo, with relative kidney weights and volumes, nephron number, and renal corpuscle size not different between groups. Furthermore, hyperoxia exposure did not significantly accelerate glomerulosclerosis in middle age. Hence, our findings show no overt long-term deleterious effects of early life hyperoxia on glomerular structure.
19
Krieger, B. P., W. H. Loomis, G. T. Czer, and R. G. Spragg. "Mechanisms of interaction between oxygen and granulocytes in hyperoxic lung injury." Journal of Applied Physiology 58, no. 4 (April 1, 1985): 1326–30. http://dx.doi.org/10.1152/jappl.1985.58.4.1326.
Full textAbstract:
Hyperoxia and infused granulocytes act synergistically in producing a nonhydrostatic high-permeability lung edema in the isolated perfused rabbit lung within 4 h, which is substantially greater than that seen with hyperoxia alone. We hypothesized that the interaction between hyperoxia and granulocytes was principally due to a direct effect of hyperoxia on the lung itself. Isolated perfused rabbit lungs that were preexposed to 2 h of hyperoxia (95% O2–5% CO2) prior to the infusion of unstimulated granulocytes (under normoxic conditions) developed significant nonhydrostatic lung edema (P = 0.008) within 2 h when compared with lungs that were preexposed to normoxia (15% O2–5% CO2) prior to granulocyte perfusion. The edema in the hyperoxic-preexposed lungs was accompanied by significant increases in bronchoalveolar lavage (BAL) protein, BAL granulocytes, BAL thromboxane and prostacyclin levels, perfusate chemotactic activity, and lung lipid peroxidation. These findings suggest that the synergistic interaction between hyperoxia and granulocytes in producing acute lung injury involves a primary effect of hyperoxia on the lung itself.
20
Lee, Sang-Min, Joseph N. McLaughlin, Daniel R. Frederick, Lin Zhu, Kalidasan Thambiayya, Karla J. Wasserloos, Iris Kaminski, et al. "Metallothionein-induced zinc partitioning exacerbates hyperoxic acute lung injury." American Journal of Physiology-Lung Cellular and Molecular Physiology 304, no. 5 (March 1, 2013): L350—L360. http://dx.doi.org/10.1152/ajplung.00243.2012.
Full textAbstract:
Hypozincemia, with hepatic zinc accumulation at the expense of other organs, occurs in infection, inflammation, and aseptic lung injury. Mechanisms underlying zinc partitioning or its impact on extrahepatic organs are unclear. Here we show that the major zinc-binding protein, metallothionein (MT), is critical for zinc transmigration from lung to liver during hyperoxia and preservation of intrapulmonary zinc during hyperoxia is associated with an injury-resistant phenotype in MT-null mice. Particularly, lung-to-liver zinc ratios decreased in wild-type (WT) and increased significantly in MT-null mice breathing 95% oxygen for 72 h. Compared with female adult WT mice, MT-null mice were significantly protected against hyperoxic lung injury indicated by reduced inflammation and interstitial edema, fewer necrotic changes to distal airway epithelium, and sustained lung function at 72 h hyperoxia. Lungs of MT-null mice showed decreased levels of immunoreactive LC3, an autophagy marker, compared with WT mice. Analysis of superoxide dismutase (SOD) activity in the lungs revealed similar levels of manganese-SOD activity between strains under normoxia and hyperoxia. Lung extracellular SOD activity decreased significantly in both strains at 72 h of hyperoxia, although there was no difference between strains. Copper-zinc-SOD activity was ∼4× higher under normoxic conditions in MT-null compared with WT mice but was not affected in either group by hyperoxia. Collectively the data suggest that genetic deletion of MT-I/II in mice is associated with compensatory increase in copper-zinc-SOD activity, prevention of hyperoxia-induced zinc transmigration from lung to liver, and hyperoxia-resistant phenotype strongly associated with differences in zinc homeostasis during hyperoxic acute lung injury.
21
Narasaraju, Telugu A., Nili Jin, Chintagari R. Narendranath, Zhongming Chen, Deming Gou, and Lin Liu. "Protein nitration in rat lungs during hyperoxia exposure: a possible role of myeloperoxidase." American Journal of Physiology-Lung Cellular and Molecular Physiology 285, no. 5 (November 2003): L1037—L1045. http://dx.doi.org/10.1152/ajplung.00008.2003.
Full textAbstract:
Several studies have suggested that exposure to hyperoxia causes lung injury through increased generation of reactive oxygen and nitrogen species. The present study was aimed to investigate the effects of hyperoxia exposure on protein nitration in lungs. Rats were exposed to hyperoxia (>95%) for 48, 60, and 72 h. Histopathological analysis showed a dramatic change in the severity of lung injury in terms of edema and hemorrhage between 48- and 60-h exposure times. Western blot for nitrotyrosine showed that several proteins with molecular masses of 29-66 kDa were nitrated in hyperoxic lung tissues. Immunohistochemical analyses indicate nitrotyrosine staining of alveolar epithelial and interstitial regions. Furthermore, immunoprecipitation followed by Western blot revealed the nitration of surfactant protein A and t1α, proteins specific for alveolar epithelial type II and type I cells, respectively. The increased myeloperoxidase (MPO) activity and total nitrite levels in bronchoalveolar lavage and lung tissue homogenates were observed in hyperoxic lungs. Neutrophils and macrophages isolated from the hyperoxia-exposed rats, when cocultured with a rat lung epithelial L2 cell line, caused a significant protein nitration in L2 cells. Inclusion of nitrite further increased the protein nitration. These studies suggest that protein nitration during hyperoxia may be mediated in part by MPO generated from activated phagocytic cells, and such protein modifications may contribute to hyperoxia-mediated lung injury.
22
Sopi, Ramadan B., Richard J. Martin, Musa A. Haxhiu, Ismail A. Dreshaj, Qin Yao, Anjum Jafri, and Syed I. A. Zaidi. "Role of brain-derived neurotrophic factor in hyperoxia-induced enhancement of contractility and impairment of relaxation in lung parenchyma." American Journal of Physiology-Lung Cellular and Molecular Physiology 295, no. 2 (August 2008): L348—L355. http://dx.doi.org/10.1152/ajplung.00067.2008.
Full textAbstract:
Prolonged hyperoxic exposure contributes to neonatal lung injury, and airway hyperreactivity is characterized by enhanced contraction and impaired relaxation of airway smooth muscle. Our previous data demonstrate that hyperoxia in rat pups upregulates expression of brain-derived neurotrophic factor (BDNF) mRNA and protein, disrupts NO-cGMP signaling, and impairs cAMP production in airway smooth muscle. We hypothesized that BDNF-tyrosine kinase B (TrkB) signaling plays a functional role in airway hyperreactivity via upregulation of cholinergic mechanisms in hyperoxia-exposed lungs. Five-day-old rat pups were exposed to ≥95% oxygen or room air for 7 days and administered daily tyrosine kinase inhibitor K-252a (50 μg·kg−1·day−1 ip) to block BDNF-TrkB signaling or vehicle. Lungs were removed for HPLC measurement of ACh or for in vitro force measurement of lung parenchymal strips. ACh content doubled in hyperoxic compared with room air-exposed lungs. K-252a treatment of hyperoxic pups restored ACh content to room air levels. Hyperoxia increased contraction and impaired relaxation of lung strips in response to incremental electrical field stimulation. K-252a administration to hyperoxic pups reversed this increase in contraction and decrease in relaxation. K-252a or TrkB-Fc was used to block the effect of exogenous BDNF in vitro. Both K-252a and TrkB-Fc blocked the effects of exogenous BDNF. Hyperoxia decreased cAMP and cGMP levels in lung strips, and blockade of BDNF-TrkB signaling restored cAMP but not cGMP to control levels. Therefore, hyperoxia-induced increase in activity of BDNF-TrkB receptor signaling appears to play a critical role in enhancing cholinergically mediated contractile responses of lung parenchyma.
23
Lagishetty, Venu, Prasanna Tamarapu Parthasarathy, Oluwakemi Phillips, Jutaro Fukumoto, Young Cho, Itsuko Fukumoto, Huynh Bao, et al. "Dysregulation of CLOCK gene expression in hyperoxia-induced lung injury." American Journal of Physiology-Cell Physiology 306, no. 11 (June 1, 2014): C999—C1007. http://dx.doi.org/10.1152/ajpcell.00064.2013.
Full textAbstract:
Hyperoxic acute lung injury (HALI) is characterized by inflammation and epithelial cell death. CLOCK genes are master regulators of circadian rhythm also implicated in inflammation and lung diseases. However, the relationship of CLOCK genes in hyperoxia-induced lung injury has not been studied. This study will determine if HALI alters CLOCK gene expression. To test this, wild-type and NALP3−/− mice were exposed to room air or hyperoxia for 24, 48, or 72 h. In addition, mice were exposed to different concentrations of hyperoxia (50, 75, or 100% O2) or room air for 72 h. The mRNA and protein levels of lung CLOCK genes, based on quantitative PCR and Western blot analysis, respectively, and their target genes are significantly elevated in mice exposed to hyperoxia compared with controls. Alterations in CLOCK genes are associated with increased inflammatory markers in bronchoalveolar lavage fluid of hyperoxic mice compared with controls. Histological examination of mice lungs exposed to hyperoxia show increased inflammation and alveolar congestion compared with controls. Our results indicate sequential increase in CLOCK gene expression in lungs of mice exposed to hyperoxia compared with controls. Additionally, data suggest a dose-dependent increase in CLOCK gene expression with increased oxygen concentrations. To validate if the expression changes related to CLOCK genes are indeed associated with inflammation, NALP3−/− was introduced to analyze loss of function in inflammation. Western blot analysis showed significant CLOCK gene downregulation in NALP3−/− mice compared with wild-type controls. Together, our results demonstrate that hyperoxia-mediated lung inflammation is associated with alterations in CLOCK gene expression.
24
Singhal, Aneesh B., Xiaoying Wang, and Eng H. Lo. "Effects of Normobaric Hyperoxia in a Rat Model of Transient Focal Cerebral Ischemia and Reperfusion." Stroke 32, suppl_1 (January 2001): 316. http://dx.doi.org/10.1161/str.32.suppl_1.316-b.
Full textAbstract:
3 Background: The role of therapeutic oxygen in treatment of acute stroke is controversial. Oxygen improves cellular aerobic metabolism and can salvage ischemic tissue. However, oxygen free radicals can increase blood brain barrier (BBB) damage, and oxygen can induce vasoconstriction, which could worsen stroke outcome. We studied the effects of normobaric oxygen in cerebral ischemia and reperfusion. Methods: Rats were subjected to normobaric hyperoxia (FiO2 100%) or normoxia (FiO2 30%) during two hour filament occlusion and one hour reperfusion of the middle cerebral artery. Twenty-four hour infarct volumes, regional cerebral blood flow (rCBF) using laser Doppler flowmetry, and severity of BBB damage (assessed by quantifying Evan’s Blue dye (EB) leakage after one hour of reperfusion) were compared between groups. Results: Physiological parameters were similar in hyperoxic and control groups, except for paO2, which was expectedly higher in the hyperoxic group (pO2 484 mm Hg) as compared to controls (pO2 118 mm Hg). Mean rCBF dropped to 25% after onset of ischemia and recovered to 75–90% after arterial unocclusion, indicating successful reperfusion. Mean total (right hemispheric) infarct volume was 65 mm 3 in the hyperoxia group and 209 mm 3 in controls, p<0.001. The reduction in infarct volume was mostly in the cortex, where mean infarct volume was 11 mm 3 in hyperoxic rats and 129 mm 3 in controls (p<0.001). Mean striatal infarct volume was 54 mm 3 in hyperoxic rats and 80 mm 3 in controls (p<0.06). Mean total EB leak was 1592 ng/g in hyperoxic and 3955 ng/g in control rats (p<0.02), suggesting reduced BBB damage in hyperoxia. However, BBB damage and EB leak are likely related to infarct volume; after normalising for infarct volume, mean EB leak was 17 ng/mm3 in the hyperoxia group and 14 ng/mm3 in controls (p=0.5). Conclusion: Total and cortical infarct volumes can be significantly reduced with normobaric hyperoxia during transient cerebral ischemia and reperfusion. Hyperoxia does not decrease blood flow to ischemic brain, and its benefit in reducing infarct volume may outweigh any potential damage from BBB damage.
25
SEPEHR, REYHANEH, SAID H. AUDI, SEPIDEH MALEKI, KEVIN STANISZEWSKI, ANNIE L. EIS, GIRIJA G. KONDURI, and MAHSA RANJI. "OPTICAL IMAGING OF LIPOPOLYSACCHARIDE-INDUCED OXIDATIVE STRESS IN ACUTE LUNG INJURY FROM HYPEROXIA AND SEPSIS." Journal of Innovative Optical Health Sciences 06, no. 03 (July 2013): 1350017. http://dx.doi.org/10.1142/s179354581350017x.
Full textAbstract:
Reactive oxygen species (ROS) have been implicated in the pathogenesis of many acute and chronic pulmonary disorders such as acute lung injury (ALI) in adults and bronchopulmonary dysplasia (BPD) in premature infants. Bacterial infection and oxygen toxicity, which result in pulmonary vascular endothelial injury, contribute to impaired vascular growth and alveolar simplification seen in the lungs of premature infants with BPD. Hyperoxia induces ALI, reduces cell proliferation, causes DNA damage and promotes cell death by causing mitochondrial dysfunction. The objective of this study was to use an optical imaging technique to evaluate the variations in fluorescence intensities of the auto-fluorescent mitochondrial metabolic coenzymes, NADH and FAD in four different groups of rats. The ratio of these fluorescence signals (NADH/FAD), referred to as NADH redox ratio (NADH RR) has been used as an indicator of tissue metabolism in injuries. Here, we investigated whether the changes in metabolic state can be used as a marker of oxidative stress caused by hyperoxia and bacterial lipopolysaccharide (LPS) exposure in neonatal rat lungs. We examined the tissue redox states of lungs from four groups of rat pups: normoxic (21% O2 ) pups, hyperoxic (90% O2 ) pups, pups treated with LPS (normoxic + LPS), and pups treated with LPS and hyperoxia (hyperoxic + LPS). Our results show that hyperoxia oxidized the respiratory chain as reflected by a ~ 31% decrease in lung tissue NADH RR as compared to that for normoxic lungs. LPS treatment alone or with hyperoxia had no significant effect on lung tissue NADH RR as compared to that for normoxic or hyperoxic lungs, respectively. Thus, NADH RR serves as a quantitative marker of oxidative stress level in lung injury caused by two clinically important conditions: hyperoxia and LPS exposure.
26
Suzuki, Yukio, Kazumi Nishio, Kei Takeshita, Osamu Takeuchi, Kenji Watanabe, Nagato Sato, Katsuhiko Naoki, Hiroyasu Kudo, Takuya Aoki, and Kazuhiro Yamaguchi. "Effect of steroid on hyperoxia-induced ICAM-1 expression in pulmonary endothelial cells." American Journal of Physiology-Lung Cellular and Molecular Physiology 278, no. 2 (February 1, 2000): L245—L252. http://dx.doi.org/10.1152/ajplung.2000.278.2.l245.
Full textAbstract:
Intercellular adhesion molecule-1 (ICAM-1) of the vascular endothelium plays a key role in the development of pulmonary oxygen toxicity. We studied the effect of steroid on hyperoxia-induced ICAM-1 expression using cultured endothelial cells in vitro. Human pulmonary artery endothelial cells (HPAECs) were cultured to confluence, and then the monolayers were exposed to either control (21% O2-5% CO2) or hyperoxic (90% O2-5% CO2) conditions with and without a synthetic glucocorticoid, methylprednisolone (MP). MP reduced hyperoxia-induced ICAM-1 and ICAM-1 mRNA expression in a dose-dependent manner. Neutrophil adhesion to hyperoxia-exposed endothelial cells was also inhibited by MP treatment. In addition, MP attenuated hyperoxia-induced H2O2 production in HPAECs as assessed by flow cytometry. An electrophoretic mobility shift assay demonstrated that hyperoxia activated nuclear factor-κB (NF-κB) but not activator protein-1 (AP-1) and that MP attenuated hyperoxia-induced NF-κB activation dose dependently. With Western immunoblot analysis, IκB-α expression was decreased by hyperoxia and increased by MP treatment. These results suggest that MP downregulates hyperoxia-induced ICAM-1 expression by inhibiting NF-κB activation via increased IκB-α expression.
27
Richter, Jute, Jaan Toelen, Jeroen Vanoirbeek, Aiko Kakigano, Philip DeKoninck, Eric Verbeken, and Jan Deprest. "Functional assessment of hyperoxia-induced lung injury after preterm birth in the rabbit." American Journal of Physiology-Lung Cellular and Molecular Physiology 306, no. 3 (February 1, 2014): L277—L283. http://dx.doi.org/10.1152/ajplung.00315.2013.
Full textAbstract:
The objective of this study was to document early neonatal (7 days) pulmonary outcome in the rabbit model for preterm birth and hyperoxia-induced lung injury. Preterm pups were delivered at 28 days (term = 31 days; early saccular phase of lung development) by cesarean section, housed in an incubator, and gavage fed for 7 days. Pups were divided into the following groups: 1) normoxia (21% O2; normoxia group) and 2) and hyperoxia (>95% O2; hyperoxia group). Controls were pups born at term who were housed in normoxic conditions (control group). Outcome measures were survival, pulmonary function tests using the whole body plethysmograph and forced oscillation technique, and lung morphometry. There was a significant difference in survival of preterm pups whether they were exposed to normoxia (83.3%) or hyperoxia (55.9%). Hyperoxic exposure was associated with increased tissue damping and elasticity and decreased static compliance compared with normoxic controls ( P < 0.01). Morphometry revealed an increased linear intercept and increased mean wall transection length, which translates to larger alveoli with septal thickening in hyperoxia compared with normoxia ( P < 0.01). In conclusion, the current experimental hyperoxic conditions to which preterm pups are exposed induce the typical clinical features of bronchopulmonary dysplasia. This model will be used to study novel preventive or therapeutic interventions.
28
Kuper-Sassé, Margaret E., Peter M. MacFarlane, Catherine A. Mayer, Richard J. Martin, Y. S. Prakash, Christina M. Pabelick, and Thomas M. Raffay. "Prenatal Maternal Lipopolysaccharide and Mild Newborn Hyperoxia Increase Intrapulmonary Airway but Not Vessel Reactivity in a Mouse Model." Children 8, no. 3 (March 5, 2021): 195. http://dx.doi.org/10.3390/children8030195.
Full textAbstract:
Maternal infection is a risk for preterm delivery. Preterm newborns often require supplemental oxygen to treat neonatal respiratory distress. Newborn hyperoxia exposure is associated with airway and vascular hyperreactivity, while the complications of maternal infection are variable. In a mouse model of prenatal maternal intraperitoneal lipopolysaccharide (LPS, embryonic day 18) with subsequent newborn hyperoxia (40% oxygen × 7 days) precision-cut living lung slices were used to measure intrapulmonary airway and vascular reactivity at 21 days of age. Hyperoxia increased airway reactivity to methacholine compared to room air controls. Prenatal maternal LPS did not alter airway reactivity in room air. Combined maternal LPS and hyperoxia exposures increased airway reactivity vs. controls, although maximal responses were diminished compared to hyperoxia alone. Vessel reactivity to serotonin did not significantly differ in hyperoxia or room air; however, prenatal maternal LPS appeared to attenuate vessel reactivity in room air. Following room air recovery, LPS with hyperoxia lungs displayed upregulated inflammatory and fibrosis genes compared to room air saline controls (TNFαR1, iNOS, and TGFβ). In this model, mild newborn hyperoxia increases airway but not vessel reactivity. Prenatal maternal LPS did not further increase hyperoxic airway reactivity. However, inflammatory genes remain upregulated weeks after recovery from maternal LPS and newborn hyperoxia exposures.
29
Moores, H. K., C. J. Beehler, M. E. Hanley, P. F. Shanley, E. E. Stevens, J. E. Repine, and L. S. Terada. "Xanthine oxidase promotes neutrophil sequestration but not injury in hyperoxic lungs." Journal of Applied Physiology 76, no. 2 (February 1, 1994): 941–45. http://dx.doi.org/10.1152/jappl.1994.76.2.941.
Full textAbstract:
Neutrophil accumulation in alveolar spaces is a conspicuous finding in hyperoxia-exposed lungs. We hypothesized that xanthine oxidase (XO)-derived oxidants contribute to retention of neutrophils in hyperoxic lungs. Rats were subjected to normobaric hyperoxia (100% O2) for 48 h, and lungs were assessed for neutrophil sequestration (morphometry and lavage cell counts) and injury (lavage albumin levels and lung weights). In rats exposed to hyperoxia, we found increased (P < 0.05) lung neutrophil retention, lavage albumin levels, and lung weights compared with normoxia-exposed control rats. Suppression of XO activity by pretreatment with allopurinol decreased (P < 0.05) lung neutrophil retention but increased (P < 0.05) lavage albumin concentrations and lung weights in hyperoxic rats. Allopurinol treatment had no effect (P > 0.05) on the numbers of macrophages or lymphocytes recoverable by lung lavage. Depletion of XO activity by an independent method, tungsten feeding, also decreased (P < 0.05) lung lavage neutrophil counts and increased (P < 0.05) lavage albumin concentrations. We conclude that XO may be involved in lung neutrophil retention but not lung injury during exposure to hyperoxia.
30
Bartman, Colleen M., Daniel Wasim Awari, Christina M. Pabelick, and Y. S. Prakash. "Intermittent Hypoxia-Hyperoxia and Oxidative Stress in Developing Human Airway Smooth Muscle." Antioxidants 10, no. 9 (August 31, 2021): 1400. http://dx.doi.org/10.3390/antiox10091400.
Full textAbstract:
Premature infants are frequently and intermittently administered supplemental oxygen during hypoxic episodes, resulting in cycles of intermittent hypoxia and hyperoxia. The relatively hypoxic in utero environment is important for lung development while hyperoxia during the neonatal period is recognized as detrimental towards the development of diseases such as bronchopulmonary dysplasia and bronchial asthma. Understanding early mechanisms that link hypoxic, hyperoxic, and intermittent hypoxic-hyperoxic exposures to altered airway structure and function are key to developing advanced therapeutic approaches in the clinic. Changes in oxygen availability can be detrimental to cellular function and contribute to oxidative damage. Here, we sought to determine the effect of oxygen on mitochondria in human fetal airway smooth muscle cells exposed to either 5% O2, 21% O2, 40% O2, or cycles of 5% and 40% O2 (intermittent hypoxia-hyperoxia). Reactive oxygen species production, altered mitochondrial morphology, and changes in mitochondrial respiration were assessed in the context of the antioxidant N-acetylcysteine. Our findings show developing airway smooth muscle is differentially responsive to hypoxic, hyperoxic, or intermittent hypoxic-hyperoxic exposure in terms of mitochondrial structure and function. Cycling O2 decreased mitochondrial branching and branch length similar to hypoxia and hyperoxia in the presence of antioxidants. Additionally, hypoxia decreased overall mitochondrial respiration while the addition of antioxidants increased respiration in normoxic and O2-cycling conditions. These studies show the necessity of balancing oxidative damage and antioxidant defense systems in the developing airway.
31
Fang, Y., F. Gao, and Z. Liu. "Angiotensin-converting enzyme 2 attenuates inflammatory response and oxidative stress in hyperoxic lung injury by regulating NF-κB and Nrf2 pathways." QJM: An International Journal of Medicine 112, no. 12 (August 8, 2019): 914–24. http://dx.doi.org/10.1093/qjmed/hcz206.
Full textAbstract:
Summary Objective To investigate the role of angiotensin-converting enzyme 2 (ACE2) in hyperoxic lung injury. Methods Adult mice were exposed to 95% O2 for 72 h to induce hyperoxic lung injury, and simultaneously treated with ACE2 agonist diminazene aceturate (DIZE) or inhibitor MLN-4760. ACE2 expression/activity in lung tissue and angiotensin (Ang)-(1–7)/Ang II in bronchoalveolar lavage fluid (BALF), and the severity of hyperoxic lung injury were evaluated. The levels of inflammatory factors in BALF and lung tissue and the expression levels of phospho-p65, p65 and IkBα were measured. Oxidative parameter and antioxidant enzyme levels in lung tissue were measured to assess oxidative stress. Finally, the expression levels of nuclear factor-erythroid-2-related factor (Nrf2), NAD(P)H quinine oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1) were measured using Western blotting. Results Hyperoxia treatment significantly decreased lung ACE2 expression/activity and increased the Ang II/Ang-(1–7) ratio, while co-treatment with hyperoxia and DIZE significantly increased lung ACE2 expression/activity and decreased the Ang II/Ang-(1–7) ratio. By contrast, co-treatment with hyperoxia and MLN-4760 significantly decreased lung ACE2 expression/activity and increased the Ang II/Ang-(1–7) ratio. Hyperoxia treatment induced significant lung injury, inflammatory response and oxidative stress, which were attenuated by DIZE but aggravated by MLN-4760. The NF-κB pathways were activated by hyperoxia and MLN-4760 but inhibited by DIZE. The Nrf2 pathway and its downstream proteins NQO1 and HO-1 were activated by DIZE but inhibited by MLN-4760. Conclusion Activation of ACE2 can reduce the severity of hyperoxic lung injury by inhibiting inflammatory response and oxidative stress. ACE2 can inhibit the NF-κB pathway and activate the Nrf2/HO-1/NQO1 pathway, which may be involved in the underlying mechanism.
32
Yang, Yan, Xian Qin, Chuangang Han, Yan Huang, Lei Jin, Qingqing Liu, and Quan Hu. "Effect of different doses of dexmedetomidine on lung function and tissue cell apoptosis in a rat model of hyperoxic acute lung injury." Tropical Journal of Pharmaceutical Research 19, no. 5 (June 29, 2020): 1093–98. http://dx.doi.org/10.4314/tjpr.v19i5.27.
Full textAbstract:
Purpose: To study the effect of different doses of dexmedetomidine on lung function and lung tissue cell apoptosis in a rat model of hyperoxic acute lung injury.
Methods: Five groups of healthy male Sprague-Dawley rats were used: normal rats, untreated hyperoxic rats, and hyperoxic rats given 3 different doses of dexmedetomidine, with 20 rats in each group. The levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were determined usingenzyme-linked immunosorbent assay (ELISA). Parietal paraffin cuts were taken from the right upper lobe for measurement of apoptosis using in situ terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and the apoptosis index was calculated.
Results: At 24 and 48 h, the levels of IL-6 and TNF-α in the hyperoxia model group were significantly higher than those in the normal control group, and their levels in the middle- and high-dose groups were markedly lowered, relative to untreated hyperoxia rats (p < 0.05). Apoptosis index in the hyperoxia model rats significantly increased, relative to normal rats (p < 0.05). The apoptosis index in the mediumand high-dose groups decreased significantly (p < 0.05).
Conclusion: Dexmedetomidine inhibits inflammatory responses caused by high concentration of oxygen inhalation, minimizes lung injury, improves lung function and inhibits lung apoptosis.
Keywords: Dexmedetomidine, Hyperoxia, Acute lung injury, Lung function, Apoptosis
33
George, Caroline L. S., Giamila Fantuzzi, Stuart Bursten, Laura Leer, and Edward Abraham. "Effects of lisofylline on hyperoxia-induced lung injury." American Journal of Physiology-Lung Cellular and Molecular Physiology 276, no. 5 (May 1, 1999): L776—L785. http://dx.doi.org/10.1152/ajplung.1999.276.5.l776.
Full textAbstract:
Lisofylline [1-(5 R-hydroxyhexyl)-3,7-dimethylxanthine] decreases lipid peroxidation in vitro and in vivo suppresses proinflammatory cytokine expression in models of lung injury due to sepsis, blood loss, and oxidative damage. In the present experiments, we used a murine hyperoxia model to examine the effects of lisofylline on the activation of nuclear transcriptional regulatory factors [nuclear factor-κB and cAMP response element binding protein (CREB)], the expression of proinflammatory cytokines in the lungs, and the circulating levels of oxidized free fatty acids as well as on hyperoxia-induced lung injury and mortality. Treatment with lisofylline inhibited hyperoxia-associated increases in tumor necrosis factor-α, interleukin-1β, and interleukin-6 in the lungs as well as decreased the levels of hyperoxia-induced serum-oxidized free fatty acids. Although hyperoxic exposure produced activation of both nuclear factor-κB and CREB in lung cell populations, only CREB activation was reduced in the mice treated with lisofylline. Lisofylline diminished hyperoxia-associated increases in lung wet-to-dry weight ratios and improved survival in animals exposed to hyperoxia. These results suggest that lisofylline ameliorates hyperoxia-induced lung injury and mortality through inhibiting CREB activation, membrane oxidation, and proinflammatory cytokine expression in the lungs.
34
Matthew, E., L. Kutcher, and J. Dedman. "Protection of lungs from hyperoxic injury: gene expression analysis of cyclosporin A therapy." Physiological Genomics 14, no. 2 (July 7, 2003): 129–38. http://dx.doi.org/10.1152/physiolgenomics.00130.2002.
Full textAbstract:
We have previously shown that cyclosporin A (CsA), an inhibitor of protein phosphatase 2B (calcineurin), attenuates hyperoxia-induced reductions in murine lung compliance. CsA protected against hyperoxia-induced changes in neutrophil infiltration, capillary congestion, edema, and hyaline membrane formation. Gene expression studies were conducted to identify the gene expression patterns underlying the protective effects of CsA during hyperoxic lung injury. After 72 h of simultaneous treatment with >95% oxygen and CsA (50 mg·kg−1·day−1), RNA was isolated from murine lungs. RNA from treated and untreated lungs was reverse transcribed to cDNA, competitively hybridized, and used to probe 8,734 complimentary DNAs on the Incyte mouse GEM 1 array. Several known genes and expressed sequence tags (ESTs) showed increased (GenBank accession numbers: AA125385, AA241295, W87197, syntaxin, and cyclin G) or decreased [AA036517, AA267567, AA217009, W82577, uteroglobin, stromal cell-derived factor 1, and surfactant protein C (SP-C)] expression after hyperoxia. Hyperoxia-stimulated reductions in SP-C gene expression were confirmed through Northern blot analysis. The increase in gene expression of one expressed sequence tag (AA125385) with hyperoxia was reversed by CsA treatment. Sequence data demonstrated that this EST has high homology to murine cyclin B1. Western blot analysis did not demonstrate any changes in distal lung cyclin B1 expression after hyperoxia. Protein expression of cyclin B1 in the distal lung was observed in the endothelial cells, bronchiolar epithelial cells, and both the type I and type II alveolar epithelial cells. Further analysis of cyclin B1 may elucidate the protective actions of CsA in hyperoxic injury.
35
Seals, D. R., D. G. Johnson, and R. F. Fregosi. "Hyperoxia lowers sympathetic activity at rest but not during exercise in humans." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 260, no. 5 (May 1, 1991): R873—R878. http://dx.doi.org/10.1152/ajpregu.1991.260.5.r873.
Full textAbstract:
The primary aim of this study was to determine the influence of systemic hyperoxia on sympathetic nervous system behavior at rest and during submaximal exercise in humans. In seven healthy subjects (aged 19-31 yr) we measured postganglionic sympathetic nerve activity to skeletal muscle (MSNA) in the leg, antecubital venous norepinephrine concentrations, heart rate, and arterial blood pressure during normoxic rest (control) followed by 3- to 4-min periods of either hyperoxic (100% O2 breathing) rest, normoxic exercise (rhythmic handgrips at 50% of maximum force), or hyperoxic exercise. During exercise, isocapnia was maintained by adding CO2 to the inspirate as necessary. At rest, hyperoxia lowered MSNA burst frequency (12-42%) and total activity (6-42%) in all subjects; the average reductions were 25 and 23%, respectively (P less than 0.05 vs. control). Heart rate also decreased during hyperoxia (6 +/- 1 beats/min, P less than 0.05), but arterial blood pressure was not affected. During hyperoxic compared with normoxic exercise, there were no differences in the magnitudes of the increases in MSNA burst frequency or total activity, plasma norepinephrine concentrations, or mean arterial blood pressure. In contrast, the increase in heart rate during hyperoxic exercise (13 +/- 2 beats/min) was less than the increase during normoxic exercise (20 +/- 2 beats/min; P less than 0.05). We conclude that, in healthy humans, systemic hyperoxia 1) lowers efferent sympathetic nerve activity to skeletal muscle under resting conditions without altering venous norepinephrine concentrations and 2) has no obvious modulatory effect on the nonactive muscle sympathetic nerve adjustments to rhythmic exercise.
36
Chavez-Valdez, Raul, Ariel Mason, Ana R. Nunes, Frances J. Northington, Clarke Tankersley, Rajni Ahlawat, Sheree M. Johnson, and Estelle B. Gauda. "Effect of hyperoxic exposure during early development on neurotrophin expression in the carotid body and nucleus tractus solitarii." Journal of Applied Physiology 112, no. 10 (May 15, 2012): 1762–72. http://dx.doi.org/10.1152/japplphysiol.01609.2011.
Full textAbstract:
Synaptic activity can modify expression of neurotrophins, which influence the development of neuronal circuits. In the newborn rat, early hyperoxia silences the synaptic activity and input from the carotid body, impairing the development and function of chemoreceptors. The purpose of this study was to determine whether early hyperoxic exposure, sufficient to induce hypoplasia of the carotid body and decrease the number of chemoafferents, would also modify neurotrophin expression within the nucleus tractus solitarii (nTS). Rat pups were exposed to hyperoxia (fraction of inspired oxygen 0.60) or normoxia until 7 or 14 days of postnatal development (PND). In the carotid body, hyperoxia decreased brain-derived neurotrophic factor (BDNF) protein expression by 93% ( P = 0.04) after a 7-day exposure, followed by a decrease in retrogradely labeled chemoafferents by 55% ( P = 0.004) within the petrosal ganglion at 14 days. Return to normoxia for 1 wk after a 14-day hyperoxic exposure did not reverse this effect. In the nTS, hyperoxia for 7 days: 1) decreased BDNF gene expression by 67% and protein expression by 18%; 2) attenuated upregulation of BDNF mRNA levels in response to acute hypoxia; and 3) upregulated p75 neurotrophic receptor, truncated tropomyosin kinase B (inactive receptor), and cleaved caspase-3. These effects were not observed in the locus coeruleus (LC). Hyperoxia for 14 days also decreased tyrosine hydroxylase levels by 18% ( P = 0.04) in nTS but not in the LC. In conclusion, hyperoxic exposure during early PND reduces neurotrophin levels in the carotid body and the nTS and shifts the balance of neurotrophic support from prosurvival to proapoptotic in the nTS, the primary brain stem site for central integration of sensory and autonomic inputs.
37
Otterbein, Leo E., Beek Yoke Chin, Lin L. Mantell, Leah Stansberry, Stuart Horowitz, and Augustine M. K. Choi. "Pulmonary apoptosis in aged and oxygen-tolerant rats exposed to hyperoxia." American Journal of Physiology-Lung Cellular and Molecular Physiology 275, no. 1 (July 1, 1998): L14—L20. http://dx.doi.org/10.1152/ajplung.1998.275.1.l14.
Full textAbstract:
Accumulating evidence demonstrates that genotoxic and oxidant stress can induce programmed cell death or apoptosis in cultured cells. However, little is known about whether oxidative stress resulting from the deleterious effects of hyperoxia can induce apoptosis in vivo and even less is known regarding the functional significance of apoptosis in vivo in response to hyperoxia. Using hyperoxia as a model of oxidant-induced lung injury in the rat, we show that hyperoxic stress results in marked apoptotic signals in the lung. Lung tissue sections obtained from rats exposed to hyperoxia exhibit increased apoptosis in a time-dependent manner by terminal transferase dUTP nick end labeling assays. To examine whether hyperoxia-induced apoptosis in the lung correlated with the extent of lung injury or tolerance (adaptation) to hyperoxia, we investigated the pattern of apoptosis with a rat model of age-dependent tolerance to hyperoxia. We show that apoptosis is associated with increased survival of aged rats to hyperoxia and with decreased levels of lung injury as measured by the volume of pleural effusion, wet-to-dry lung weight, and myeloperoxidase content in aged rats compared with young rats after hyperoxia. We also examined this relationship in an alternate model of tolerance to hyperoxia. Lipopolysaccharide (LPS)-treated young rats not only demonstrated tolerance to hyperoxia but also exhibited a significantly lower apoptotic index compared with saline-treated rats after hyperoxia. To further separate the effects of aging and tolerance, we show that aged rats pretreated with LPS did not exhibit a significant level of tolerance against hyperoxia. Furthermore, similar to the hyperoxia-tolerant LPS-pretreated young rats, the nontolerant LPS-pretreated aged rats also exhibited a significantly reduced apoptotic index compared with aged rats exposed to hyperoxia alone. Taken together, our data suggest that hyperoxia-induced apoptosis in vivo can be modulated by both aging and tolerance effects. We conclude that there is no overall relationship between apoptosis and tolerance.
38
Hughson, Richard L., and John M. Kowalchuk. "Kinetics of Oxygen Uptake for Submaximal Exercise in Hyperoxia, Normoxia, and Hypoxia." Canadian Journal of Applied Physiology 20, no. 2 (June 1, 1995): 198–210. http://dx.doi.org/10.1139/h95-014.
Full textAbstract:
This study evaluated the dynamic response of [Formula: see text] in 6 healthy men at the onset and end of submaximal step changes in work rate during a pseudorandom binary sequence (PRBS) exercise test and during ramp incremental exercise to exhaustion while breathing three different gas mixtures. The fractional concentrations of inspired O2 were 0.14, 0.21, and 0.70 for the hypoxic, normoxic, and hyperoxic tests, respectively. Both maximal [Formula: see text] and work rate was significantly reduced in hypoxic tests compared to normoxic and hyperoxic tests. Maximal work rate was greater in hyperoxia than in normoxia. Work rate at ventilatory threshold was lower in hypoxia than in normoxia and hyperoxia but above the upper limit of exercise for the submaximal tests. Hypoxia significantly slowed the response of [Formula: see text] both at the onset and end of exercise compared to normoxia and hyperoxia. Hypoxia also modified the response to PRBS exercise, and again there was no difference between normoxia and hyperoxia. These data support the concept that [Formula: see text] kinetics can be slowed from the normoxic response by a hypoxic gas mixture. Key words: [Formula: see text]max, ventilatory threshold, oxygen deficit, pseudorandom binary sequence
39
Tyurina, Yulia Y., Vladimir A. Tyurin, A. Murat Kaynar, Valentyna I. Kapralova, Karla Wasserloos, Jin Li, Mackenzie Mosher, et al. "Oxidative lipidomics of hyperoxic acute lung injury: mass spectrometric characterization of cardiolipin and phosphatidylserine peroxidation." American Journal of Physiology-Lung Cellular and Molecular Physiology 299, no. 1 (July 2010): L73—L85. http://dx.doi.org/10.1152/ajplung.00035.2010.
Full textAbstract:
Reactive oxygen species have been shown to play a significant role in hyperoxia-induced acute lung injury, in part, by inducing apoptosis of pulmonary endothelium. However, the signaling roles of phospholipid oxidation products in pulmonary endothelial apoptosis have not been studied. Using an oxidative lipidomics approach, we identified individual molecular species of phospholipids involved in the apoptosis-associated peroxidation process in a hyperoxic lung. C57BL/6 mice were killed 72 h after exposure to hyperoxia (100% oxygen). We found that hyperoxia-induced apoptosis (documented by activation of caspase-3 and -7 and histochemical terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling staining of pulmonary endothelium) was accompanied by nonrandom oxidation of pulmonary lipids. Two anionic phospholipids, mitochondria-specific cardiolipin (CL) and extramitochondrial phosphatidylserine (PS), were the two major oxidized phospholipids in hyperoxic lung. Using electrospray ionization mass spectrometry, we identified several oxygenation products in CL and PS. Quantitative assessments revealed a significant decrease of CL and PS molecular species containing C18:2, C20:4, C22:5, and C22:6 fatty acids. Similarly, exposure of mouse pulmonary endothelial cells (MLEC) to hyperoxia (95% oxygen; 72 h) resulted in activation of caspase-3 and -7 and significantly decreased the content of CL molecular species containing C18:2 and C20:4 as well as PS molecular species containing C22:5 and C22:6. Oxygenated molecular species were found in the same two anionic phospholipids, CL and PS, in MLEC exposed to hyperoxia. Treatment of MLEC with a mitochondria-targeted radical scavenger, a conjugate of hemi-gramicidin S with nitroxide, XJB-5-131, resulted in significantly lower oxidation of both CL and PS and a decrease in hyperoxia-induced changes in caspase-3 and -7 activation. We speculate that cytochrome c driven oxidation of CL and PS is associated with the signaling role of these oxygenated species participating in the execution of apoptosis and clearance of pulmonary endothelial cells, thus contributing to hyperoxic lung injury.
40
Hambraeus-Jonzon, K., L. Bindslev, C. Frostell, and G. Hedenstierna. "Individual lung blood flow during unilateral hypoxia: effects of inhaled nitric oxide." European Respiratory Journal 11, no. 3 (March 1, 1998): 565–70. http://dx.doi.org/10.1183/09031936.98.11030565.
Full textAbstract:
We hypothesized that the diversion of blood away from a hypoxic lung to the opposite oxygenated lung can be enhanced by inhaling nitric oxide (NO) into the oxygenated lung. We measured individual lung blood flow when 50 ppm NO was selectively inhaled to: a hyperoxic lung during contralateral hypoxia; a normoxic lung during bilateral normoxia; and a hyperoxic lung during bilateral hyperoxia. Twenty two patients with healthy lungs were studied during intravenous anaesthesia. The lungs were separately and synchronously ventilated. The relative perfusion of each lung was assessed by the inert gas elimination technique. Unilateral hypoxic (inspiratory oxygen fraction (FI,O2) 0.05) ventilation during contralateral hyperoxia reduced the perfusion of the hypoxic lung from a mean (SD) of 47 (9)% of cardiac output (Q'), to 30 (7)% (p<0.001) of Q'. NO inhalation to the hyperoxic lung increased its blood flow from 70 (7)% to 75 (6)% (p<0.05) of Q', and reduced the blood flow to the hypoxic lung to 25 (6)% (p<0.05). Unilateral NO inhalation during bilateral normoxia or hyperoxia had no effect on pulmonary blood flow distribution. Nitric oxide inhalation to a hyperoxic lung increases the perfusion to this lung by redistribution of blood flow if the opposite lung is hypoxic.
41
Elsaie, Ahmed, Renuka T. Menon, Amrit K. Shrestha, Sharada H. Gowda, Nidhy P. Varghese, Roberto J. Barrios, Cynthia L. Blanco, Girija G. Konduri, and Binoy Shivanna. "Endothelial Adenosine Monophosphate-Activated Protein Kinase-Alpha1 Deficiency Potentiates Hyperoxia-Induced Experimental Bronchopulmonary Dysplasia and Pulmonary Hypertension." Antioxidants 10, no. 12 (November 29, 2021): 1913. http://dx.doi.org/10.3390/antiox10121913.
Full textAbstract:
Bronchopulmonary dysplasia and pulmonary hypertension, or BPD-PH, are serious chronic lung disorders of prematurity, without curative therapies. Hyperoxia, a known causative factor of BPD-PH, activates adenosine monophosphate-activated protein kinase (AMPK) α1 in neonatal murine lungs; however, whether this phenomenon potentiates or mitigates lung injury is unclear. Thus, we hypothesized that (1) endothelial AMPKα1 is necessary to protect neonatal mice against hyperoxia-induced BPD-PH, and (2) AMPKα1 knockdown decreases angiogenesis in hyperoxia-exposed neonatal human pulmonary microvascular endothelial cells (HPMECs). We performed lung morphometric and echocardiographic studies on postnatal day (P) 28 on endothelial AMPKα1-sufficient and -deficient mice exposed to 21% O2 (normoxia) or 70% O2 (hyperoxia) from P1–P14. We also performed tubule formation assays on control- or AMPKα1-siRNA transfected HPMECs, exposed to 21% O2 or 70% O2 for 48 h. Hyperoxia-mediated alveolar and pulmonary vascular simplification, pulmonary vascular remodeling, and PH were significantly amplified in endothelial AMPKα1-deficient mice. AMPKα1 siRNA knocked down AMPKα1 expression in HPMECs, and decreased their ability to form tubules in normoxia and hyperoxia. Furthermore, AMPKα1 knockdown decreased proliferating cell nuclear antigen expression in hyperoxic conditions. Our results indicate that AMPKα1 is required to reduce hyperoxia-induced BPD-PH burden in neonatal mice, and promotes angiogenesis in HPMECs to limit lung injury.
42
Becker, Heinrich F., Olli Polo, Stephen G. McNamara, Michael Berthon-Jones, and Colin E. Sullivan. "Effect of different levels of hyperoxia on breathing in healthy subjects." Journal of Applied Physiology 81, no. 4 (October 1, 1996): 1683–90. http://dx.doi.org/10.1152/jappl.1996.81.4.1683.
Full textAbstract:
Becker, Heinrich F., Olli Polo, Stephen G. McNamara, Michael Berthon-Jones, and Colin E. Sullivan. Effect of different levels of hyperoxia on breathing in healthy subjects. J. Appl. Physiol. 81(4): 1683–1690, 1996.—We have recently shown that breathing 50% O2 markedly stimulates ventilation in healthy subjects if end-tidal [Formula: see text]([Formula: see text]) is maintained. The aim of this study was to investigate a possible dose-dependent stimulation of ventilation by O2 and to examine possible mechanisms of hyperoxic hyperventilation. In eight normal subjects ventilation was measured while they were breathing 30 and 75% O2 for 30 min, with[Formula: see text] being held constant. Acute hypercapnic ventilatory responses were also tested in these subjects. The 75% O2 experiment was repeated without controlling[Formula: see text] in 14 subjects, and in 6 subjects arterial blood gases were taken at baseline and at the end of the hyperoxia period. Minute ventilation (V˙i) increased by 21 and 115% with 30 and 75% isocapnic hyperoxia, respectively. The 75% O2 without any control on[Formula: see text] led to a 16% increase inV˙i, but[Formula: see text] decreased by 3.6 Torr (9%). There was a linear correlation ( r = 0.83) between the hypercapnic and the hyperoxic ventilatory response. In conclusion, isocapnic hyperoxia stimulates ventilation in a dose-dependent way, withV˙i more than doubling after 30 min of 75% O2. If isocapnia is not maintained, hyperventilation is attenuated by a decrease in arterial[Formula: see text]. There is a correlation between hyperoxic and hypercapnic ventilatory responses. On the basis of data from the literature, we concluded that the Haldane effect seems to be the major cause of hyperventilation during both isocapnic and poikilocapnic hyperoxia.
43
Leitch, Patricia, Anthony Hudson, Jo Griggs, Ewoud ter Avest, Renate Stolmeiger, and Richard Lyon. "1048 Incidence of hyperoxia in traumatically injured patients receiving pre-hospital emergency anaesthesia: a 5-year retrospective analysis." Emergency Medicine Journal 39, no. 3 (February 21, 2022): 264.1–264. http://dx.doi.org/10.1136/emermed-2022-rcem.41.
Full textAbstract:
Aims/Objectives/BackgroundPrevious studies have demonstrated an association between hyperoxia and increased mortality in various patient conditions. In the present study, we aim to investigate the incidence of hyperoxia in trauma patients receiving PHEA, and we aim to determine factors that may help guide prehospital oxygen administration.Methods/DesignA retrospective cohort study was performed of all patients who received PHEA by a single helicopter emergency medical service (HEMS) service between 1 October 2014 and 1 May 2019 and who were subsequently transferred to one major trauma centre (MTC). Patient and treatment factors were collected from the electronic patient records of the HEMS service and the hospital. Hyperoxia was defined as a PaO2 >16, based on the first arterial blood gas analysis upon arrival to hospital.Results/ConclusionsOn presentation to the MTC, the majority of the patients (90/147, 61,2%) had severe hyperoxia, 30 patients (20.4%) had mild hyperoxia, 26 patients (19.7%) had normoxia, and 1 patient (0.7%) had hypoxia. The median [IQR] PaO2 in the first ABGA after HEMS handover was 36.7 [18.5–52.2] kPa, with a range of 7.0–86.0 kPa. SpO2 readings before handover were independently associated with presence of hyperoxia. An SpO2 ≥97% was associated with significantly increased odds of hyperoxia (OR 3.99 [1.58–10.08], and had a sensitivity of 86.7 [79.1–92.4]%, specificity of 37.9 [20.7–57.8]%, positive predictive value of 84.5 [70.2–87.9]% and a negative predictive value of 42.3 [27.4–58.7]% for presence of hyperoxemia. HEMS oxygenation strategies are effective; trauma patients who have undergone PHEA often have a profound hyperoxemia upon arrival in hospital. In the prehospital setting where ABGA is not readily available, target SpO2 of 94–98% as recommended in BTS Guidelines should guide FiO2 titration to reduce risk of tissue hyperoxia. Predeparture checklists should include an agreed system to adjust FiO2 according to a patient’s SpO2 rather than fixed concentration.
44
Casey, Darren P., Michael J. Joyner, Paul L. Claus, and Timothy B. Curry. "Vasoconstrictor responsiveness during hyperbaric hyperoxia in contracting human muscle." Journal of Applied Physiology 114, no. 2 (January 15, 2013): 217–24. http://dx.doi.org/10.1152/japplphysiol.01197.2012.
Full textAbstract:
Large increases in systemic oxygen content cause substantial reductions in exercising forearm blood flow (FBF) due to increased vascular resistance. We hypothesized that 1) functional sympatholysis (blunting of sympathetic α-adrenergic vasoconstriction) would be attenuated during hyperoxic exercise and 2) α-adrenergic blockade would limit vasoconstriction during hyperoxia and increase FBF to levels observed under normoxic conditions. Nine male subjects (age 28 ± 1 yr) performed forearm exercise (20% of maximum) under normoxic and hyperoxic conditions. Studies were performed in a hyperbaric chamber at 1 atmosphere absolute (ATA; sea level) while breathing 21% O2 and at 2.82 ATA while breathing 100% O2 (estimated change in arterial O2 content ∼6 ml O2/100 ml). FBF (ml/min) was measured using Doppler ultrasound. Forearm vascular conductance (FVC) was calculated from FBF and blood pressure (arterial catheter). Vasoconstrictor responsiveness was determined using intra-arterial tyramine. FBF and FVC were substantially lower during hyperoxic exercise than normoxic exercise (∼20–25%; P < 0.01). At rest, vasoconstriction to tyramine (% decrease from pretyramine values) did not differ between normoxia and hyperoxia ( P > 0.05). During exercise, vasoconstrictor responsiveness was slightly greater during hyperoxia than normoxia (−22 ± 3 vs. −17 ± 2%; P < 0.05). However, during α-adrenergic blockade, hyperoxic exercise FBF and FVC remained lower than during normoxia ( P < 0.01). Therefore, our data suggest that although the vasoconstrictor responsiveness during hyperoxic exercise was slightly greater, it likely does not explain the majority of the large reductions in FBF and FVC (∼20–25%) during hyperbaric hyperoxic exercise.
45
Baleeiro, Carlos E. O., Paul J. Christensen, Susan B. Morris, Michael P. Mendez, Steven E. Wilcoxen, and Robert Paine. "GM-CSF and the impaired pulmonary innate immune response following hyperoxic stress." American Journal of Physiology-Lung Cellular and Molecular Physiology 291, no. 6 (December 2006): L1246—L1255. http://dx.doi.org/10.1152/ajplung.00016.2006.
Full textAbstract:
We have previously demonstrated that mice exposed to sublethal hyperoxia (an atmosphere of >95% oxygen for 4 days, followed by return to room air) have significantly impaired pulmonary innate immune response. Alveolar macrophages (AM) from hyperoxia-exposed mice exhibit significantly diminished antimicrobial activity and markedly reduced production of inflammatory cytokines in response to stimulation with LPS compared with AM from control mice in normoxia. As a consequence of these defects, mice exposed to sublethal hyperoxia are more susceptible to lethal pneumonia with Klebsiella pneumoniae than control mice. Granulocyte/macrophage colony-stimulating factor (GM-CSF) is a growth factor produced by normal pulmonary alveolar epithelial cells that is critically involved in maintenance of normal AM function. We now report that sublethal hyperoxia in vivo leads to greatly reduced alveolar epithelial cell GM-CSF expression. Systemic treatment of mice with recombinant murine GM-CSF during hyperoxia exposure preserved AM function, as indicated by cell surface Toll-like receptor 4 expression and by inflammatory cytokine secretion following stimulation with LPS ex vivo. Treatment of hyperoxic mice with GM-CSF significantly reduced lung bacterial burden following intratracheal inoculation with K. pneumoniae, returning lung bacterial colony-forming units to the level of normoxic controls. These data point to a critical role for continuous GM-CSF activity in the lung in maintenance of normal AM function and demonstrate that lung injury due to hyperoxic stress results in significant impairment in pulmonary innate immunity through suppression of alveolar epithelial cell GM-CSF expression.
46
Kawamura, Tomohiro, Nobunao Wakabayashi, Norihisa Shigemura, Chien-Sheng Huang, Kosuke Masutani, Yugo Tanaka, Kentaro Noda, et al. "Hydrogen gas reduces hyperoxic lung injury via the Nrf2 pathway in vivo." American Journal of Physiology-Lung Cellular and Molecular Physiology 304, no. 10 (May 15, 2013): L646—L656. http://dx.doi.org/10.1152/ajplung.00164.2012.
Full textAbstract:
Hyperoxic lung injury is a major concern in critically ill patients who receive high concentrations of oxygen to treat lung diseases. Successful abrogation of hyperoxic lung injury would have a huge impact on respiratory and critical care medicine. Hydrogen can be administered as a therapeutic medical gas. We recently demonstrated that inhaled hydrogen reduced transplant-induced lung injury and induced heme oxygenase (HO)-1. To determine whether hydrogen could reduce hyperoxic lung injury and investigate the underlying mechanisms, we randomly assigned rats to four experimental groups and administered the following gas mixtures for 60 h: 98% oxygen (hyperoxia), 2% nitrogen; 98% oxygen (hyperoxia), 2% hydrogen; 98% balanced air (normoxia), 2% nitrogen; and 98% balanced air (normoxia), 2% hydrogen. We examined lung function by blood gas analysis, extent of lung injury, and expression of HO-1. We also investigated the role of NF-E2-related factor (Nrf) 2, which regulates HO-1 expression, by examining the expression of Nrf2-dependent genes and the ability of hydrogen to reduce hyperoxic lung injury in Nrf2-deficient mice. Hydrogen treatment during exposure to hyperoxia significantly improved blood oxygenation, reduced inflammatory events, and induced HO-1 expression. Hydrogen did not mitigate hyperoxic lung injury or induce HO-1 in Nrf2-deficient mice. These findings indicate that hydrogen gas can ameliorate hyperoxic lung injury through induction of Nrf2-dependent genes, such as HO-1. The findings suggest a potentially novel and applicable solution to hyperoxic lung injury and provide new insight into the molecular mechanisms and actions of hydrogen.
47
O'Reilly, Michael A., Rhonda J. Staversky, Jacob N. Finkelstein, and Peter C. Keng. "Activation of the G2 cell cycle checkpoint enhances survival of epithelial cells exposed to hyperoxia." American Journal of Physiology-Lung Cellular and Molecular Physiology 284, no. 2 (February 1, 2003): L368—L375. http://dx.doi.org/10.1152/ajplung.00299.2002.
Full textAbstract:
Reactive oxygen species produced during hyperoxia damage DNA, inhibit proliferation in G1- through p53-dependent activation of p21Cip1/WAF1/Sdi1, and kill cells. Because checkpoint activation protects cells from genotoxic stress, we investigated cell proliferation and survival of the murine type II epithelial cell line MLE15 during hyperoxia. These cells were chosen for study because they express Simian large and small-T antigens, which transform cells in part by disrupting the p53-dependent G1 checkpoint. Cell counts, 5-bromo-2′-deoxyuridine labeling, and flow cytometry revealed that hyperoxia slowed cell cycle progression after one replication, resulting in a pronounced G2 arrest by 72 h. Addition of caffeine, which inactivates the G2 checkpoint, diminished the percentage of hyperoxic cells in G2 and increased the percentage in sub-G1 and G1. Abrogation of the G2 checkpoint was associated with enhanced oxygen-induced DNA strand breaks and cell death. Caffeine did not affect DNA integrity or viability of cells exposed to room air. Similarly, caffeine abrogated the G2 checkpoint in hyperoxic A549 epithelial cells and enhanced oxygen-induced toxicity. These data indicate that hyperoxia rapidly inhibits proliferation after one cell cycle and that the G2 checkpoint is critical for limiting DNA damage and cell death.
48
Yang, Guang, Maurice D. Hinson, Jessica E. Bordner, Qing S. Lin, Amal P. Fernando, Ping La, Clyde J. Wright, and Phyllis A. Dennery. "Silencing hyperoxia-induced C/EBPα in neonatal mice improves lung architecture via enhanced proliferation of alveolar epithelial cells." American Journal of Physiology-Lung Cellular and Molecular Physiology 301, no. 2 (August 2011): L187—L196. http://dx.doi.org/10.1152/ajplung.00082.2011.
Full textAbstract:
Postnatal lung development requires proliferation and differentiation of specific cell types at precise times to promote proper alveolar formation. Hyperoxic exposure can disrupt alveolarization by inhibiting cell growth; however, it is not fully understood how this is mediated. The transcription factor CCAAT/enhancer binding protein-α (C/EBPα) is highly expressed in the lung and plays a role in cell proliferation and differentiation in many tissues. After 72 h of hyperoxia, C/EBPα expression was significantly enhanced in the lungs of newborn mice. The increased C/EBPα protein was predominantly located in alveolar type II cells. Silencing of C/EBPα with a transpulmonary injection of C/EBPα small interfering RNA (siRNA) prior to hyperoxic exposure reduced expression of markers of type I cell and differentiation typically observed after hyperoxia but did not rescue the altered lung morphology at 72 h. Nevertheless, when C/EBPα hyperoxia-exposed siRNA-injected mice were allowed to recover for 2 wk in room air, lung epithelial cell proliferation was increased and lung morphology was restored compared with hyperoxia-exposed control siRNA-injected mice. These data suggest that C/EBPα is an important regulator of postnatal alveolar epithelial cell proliferation and differentiation during injury and repair.
49
Ariyaratnam, Priyadharshanan, Mahmoud Loubani, Robert Bennett, Steven Griffin, Mubarak A. Chaudhry, Michael E. Cowen, Levant Guvendik, Alexander R. J. Cale, and Alyn H. Morice. "Hyperoxic Vasoconstriction of Human Pulmonary Arteries: A Novel Insight into Acute Ventricular Septal Defects." ISRN Cardiology 2013 (March 31, 2013): 1–4. http://dx.doi.org/10.1155/2013/685735.
Full textAbstract:
Objectives. Acute rises in pulmonary artery pressures following postinfarction ventricular septal defects present a challenge. We hypothesised that the abnormally high oxygen content exposure to the pulmonary arteries may be a factor. We investigated the contractile responses of human pulmonary arteries to changes in oxygen tension. Methods. Isometric tension was measured in large and medium sized pulmonary artery rings obtained from lung resections for patients with bronchial carcinoma (n=30). Fresh rings were mounted in organ baths bubbled under basal conditions with hyperoxic or normoxic gas mixes and the gas tensions varied during the experiment. We studied whether voltage-gated calcium channels and nitric oxide signalling had any role in responses to oxygen changes. Results. Hypoxia caused a net mean relaxation of 18.1% ± 15.5 (P<0.005) from hyperoxia. Subsequent hyperoxia caused a contraction of 19.2% ± 13.5 (P<0.005). Arteries maintained in normoxia responded to hyperoxia with a mean constriction of 14.8% ± 3.9 (P<0.005). Nifedipine inhibited the vasoconstrictive response (P<0.05) whilst L-NAME had no effect on any hypoxic vasodilatory response. Conclusions. We demonstrate that hyperoxia leads to vasoconstriction in human pulmonary arteries. The mechanism appears to be dependent on voltage-gated calcium channels. Hyperoxic vasoconstriction may contribute to acute rises in pulmonary artery pressures.
50
Ranadive, Sushant M., Michael J. Joyner, Branton G. Walker, Jennifer L. Taylor, and Darren P. Casey. "Effect of vitamin C on hyperoxia-induced vasoconstriction in exercising skeletal muscle." Journal of Applied Physiology 117, no. 10 (November 15, 2014): 1207–11. http://dx.doi.org/10.1152/japplphysiol.00073.2014.
Full textAbstract:
Hyperoxia can cause substantial reductions in peripheral and coronary blood flow at rest and during exercise, which may be caused by reactive oxygen species (ROS) generated during hyperoxia. The aim of this study was to investigate the role of ROS in hyperoxia-induced reductions in skeletal muscle blood flow during forearm exercise. We hypothesized that infusion of vitamin C would abolish the effects of hyperoxia on the forearm blood flow (FBF) responses to exercise. Twelve young healthy adults performed rhythmic forearm handgrip exercise (10% of maximum voluntary contraction for 5 min) during normoxia and hyperoxia. For each condition, two trials were conducted with intra-arterial administration of saline or vitamin C. FBF was measured using Doppler ultrasound. During hyperoxia with saline, FBF and forearm vascular conductance (FVC) were 86.3 ± 5.1 and 86.8 ± 5.2%, respectively, of the normoxic values (100%) ( P < 0.05). During vitamin C, hyperoxic FBF and FVC responses were 90.9 ± 4.2 and 90.9 ± 4.1%, respectively, of the normoxic values ( P = 0.57 and 0.59). Subjects were then divided into three subgroups based on their percent decrease in FBF (>20, 10–20, and <10%) during hyperoxia. In the subgroup that demonstrated the greatest hyperoxia-induced changes (>20%), FBF and FVC during hyperoxia were 67.1 ± 4.0 and 66.8 ± 3.6%, respectively, of the normoxic values. Vitamin C abolished these effects on FBF and FVC with values that were 102.0 ± 5.2 and 100.8 ± 6.1%, respectively. However, vitamin C had no effect in the other two subgroups. This analysis is consistent with the idea that ROS generation blunts the FBF responses to exercise in the subjects most affected by hyperoxia.