Diss. (sammanfattning) Linköping : Linköpings universitet, 2005. / Härtill 4 uppsatser.

Xu Feng. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (p. 205-233). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

PURPOSE: Systemic hyperoxia has been induced using inspired gases in many studies to investigate vascular reactivity in the retinal vasculature. Technical limitations in the past resulted in inadequate control of systemic partial pressures of O2 and CO2, the latter of which tended to decrease secondary to induced hyperoxia. Recent development of a computerized gas delivery instrument has enabled the specific control of end-tidal CO2 (ETCO2) and fractional expired O2 (FeO2), independent of each other and of minute ventilation. The specific aims of each chapter are as follows: Chapter 3: To compare the magnitude and variability of the retinal vascular reactivity response to an isocapnic hyperoxic stimulus delivered using a manually-operated method to the newly developed computer-controlled gas sequencer. Chapter 4: To investigate the retinal hemodynamic response to incremental changes in hyperoxic stimuli during isocapnia. METHODS: Chapter 3: Ten young, healthy adults inhaled gases in a sequence of normoxic baseline, isocapnic hyperoxia, and normoxic recovery, using both gas delivery systems in random order. Chapter 4: Twelve healthy, young adults participated in a gas protocol consisting of 4 phases at varying fractional expired oxygen levels (FeO2): baseline (15%), hyperoxia I (40%), hyperoxia II (65%), and recovery (15%). End-tidal carbon dioxide (ETCO2) was maintained at an isocapnic level (~ 5%) throughout the experiment. In both Chapters 3 and 4, blood flow was derived from retinal arteriolar diameter and simultaneous blood velocity measurements of the superior temporal arteriole, acquired at 1-minute intervals during each of the phases of the gas protocol. RESULTS: Chapter 3: There was no interaction effect between the phases and gas delivery methods (p = 0.7718), but ETCO2 was significantly reduced during hyperoxia (p = 0.0002) for both methods. However, the magnitude of change in ETCO2 was physiologically insignificant i.e. <1%. The two systems differed in terms of FeO2 during hyperoxia, at a level of 85.27 ± 0.29% for the manual method, and 69.02 ± 2.84% for the computer method (p < 0.05). Despite this difference in oxygen concentrations, there was no difference in the vascular reactivity response for diameter (p = 0.7756), velocity (p = 0.1176), and flow (p = 0.1885) for equivalent gas phases between the two gas delivery systems. The inter-subject variability of retinal hemodynamic parameters was consistently lower using the computer-controlled gas sequencer. Chapter 4: Repeated measures ANOVA showed that there were significant influences of incremental changes in FeO2 on arteriolar diameter (p < 0.0001), blood velocity (p < 0.0001), and blood flow (p < 0.0001) in the retina. Paired t-tests of these retinal hemodynamic parameters during each phase in the gas sequence showed they were significantly different (p < 0.05) from each other, with the exception of baseline and recovery values. Incremental increases in FeO2 caused a linear decrease in group mean arteriolar diameter (R2 = 1, p = 0.002), group mean blood velocity (R2 = 0.9968, p = 0.04), and group mean blood flow (R2 = 0.9982, p= 0.03). CONCLUSIONS: Chapter 3: Inter-subject variability for virtually all retinal hemodynamic parameters was reduced using the computer-controlled method, presumably due to a higher degree of gas control. However, care needs to be exercised in the interprtetation of these results due to the relatively small sample size. A similar retinal hemodynamic response to isocapnic hyperoxia was induced using the two gas delivery systems, despite different levels of maximal FeO2. Chapter 4: Isocapnic hyperoxia elicits vasoconstriction and the reduction of retinal arteriolar blood flow in a dose-dependent manner over the range of FeO2 explored in this study.

PURPOSE: Systemic hyperoxia has been induced using inspired gases in many studies to investigate vascular reactivity in the retinal vasculature. Technical limitations in the past resulted in inadequate control of systemic partial pressures of O2 and CO2, the latter of which tended to decrease secondary to induced hyperoxia. Recent development of a computerized gas delivery instrument has enabled the specific control of end-tidal CO2 (ETCO2) and fractional expired O2 (FeO2), independent of each other and of minute ventilation. The specific aims of each chapter are as follows: Chapter 3: To compare the magnitude and variability of the retinal vascular reactivity response to an isocapnic hyperoxic stimulus delivered using a manually-operated method to the newly developed computer-controlled gas sequencer. Chapter 4: To investigate the retinal hemodynamic response to incremental changes in hyperoxic stimuli during isocapnia. METHODS: Chapter 3: Ten young, healthy adults inhaled gases in a sequence of normoxic baseline, isocapnic hyperoxia, and normoxic recovery, using both gas delivery systems in random order. Chapter 4: Twelve healthy, young adults participated in a gas protocol consisting of 4 phases at varying fractional expired oxygen levels (FeO2): baseline (15%), hyperoxia I (40%), hyperoxia II (65%), and recovery (15%). End-tidal carbon dioxide (ETCO2) was maintained at an isocapnic level (~ 5%) throughout the experiment. In both Chapters 3 and 4, blood flow was derived from retinal arteriolar diameter and simultaneous blood velocity measurements of the superior temporal arteriole, acquired at 1-minute intervals during each of the phases of the gas protocol. RESULTS: Chapter 3: There was no interaction effect between the phases and gas delivery methods (p = 0.7718), but ETCO2 was significantly reduced during hyperoxia (p = 0.0002) for both methods. However, the magnitude of change in ETCO2 was physiologically insignificant i.e. <1%. The two systems differed in terms of FeO2 during hyperoxia, at a level of 85.27 ± 0.29% for the manual method, and 69.02 ± 2.84% for the computer method (p < 0.05). Despite this difference in oxygen concentrations, there was no difference in the vascular reactivity response for diameter (p = 0.7756), velocity (p = 0.1176), and flow (p = 0.1885) for equivalent gas phases between the two gas delivery systems. The inter-subject variability of retinal hemodynamic parameters was consistently lower using the computer-controlled gas sequencer. Chapter 4: Repeated measures ANOVA showed that there were significant influences of incremental changes in FeO2 on arteriolar diameter (p < 0.0001), blood velocity (p < 0.0001), and blood flow (p < 0.0001) in the retina. Paired t-tests of these retinal hemodynamic parameters during each phase in the gas sequence showed they were significantly different (p < 0.05) from each other, with the exception of baseline and recovery values. Incremental increases in FeO2 caused a linear decrease in group mean arteriolar diameter (R2 = 1, p = 0.002), group mean blood velocity (R2 = 0.9968, p = 0.04), and group mean blood flow (R2 = 0.9982, p= 0.03). CONCLUSIONS: Chapter 3: Inter-subject variability for virtually all retinal hemodynamic parameters was reduced using the computer-controlled method, presumably due to a higher degree of gas control. However, care needs to be exercised in the interprtetation of these results due to the relatively small sample size. A similar retinal hemodynamic response to isocapnic hyperoxia was induced using the two gas delivery systems, despite different levels of maximal FeO2. Chapter 4: Isocapnic hyperoxia elicits vasoconstriction and the reduction of retinal arteriolar blood flow in a dose-dependent manner over the range of FeO2 explored in this study.

An association between major surgery in the elderly and precipitation of Alzheimers disease (AD) has been reported. Hyperoxia (100%) oxygen is commonly administered after surgery to increase the oxygen content of blood. However, hyperoxia is a potent cerebral vasoconstrictor and generator of free radicals, as is [beta]amyloid (A[beta];). This study was aimed at examining behavioral, neuropathological, and neurochemical effects of hyperoxia treatments in APPsw transgenic mice (Tg+), which have elevated brain A[beta]; levels by 3-4 months of age but are not yet cognitively-impaired. At 3 months of age, Tg+ mice were pre-tested in the radial arm water maze (RAWM) task of working memory and found to be unimpaired. At 4.5 months of age, half of the Tg+ mice received the first of 3 equally-spaced hyperoxia sessions (3 hrs each) given over the ensuing 3 months. The other half of the Tg+ mice were exposed to compressed air during these 3 sessions. RAWM testing performed immediately following the final gas session at 7.5 months of age revealed significant working memory impairment in Tg+ mice exposed to hyperoxia. The Tg+ group that was exposed to placebo treatment showed a trend towards impairment, however, was not significantly different from the non-transgenic group. Hyperoxia-induced memory impairment in Tg+ mice did not involve changes in brain A[beta] deposition, degenerative cell numbers in hippocampus, neocortical lipid peroxidation, or hippocampal levels of APP, ApoE, COX-2, or GFAP. The combination of excess A[beta] and hyperoxia could have induced greater oxidative stress and cerebral vasoconstriction than either one alone, resulting in a pathologic cerebral hypoperfusion that triggered subsequent cognitive impairment.

Hyperoxia is an essential aid to life support in patients with severe respiratory failure. However, it is recognised as a contributor to the pathological consequences of oxidative stress including oxidative tissue damage, inflammation and cell death resulting in acute or chronic lung injury. The specific mechanisms behind this type of injury are still not completely understood. This study was undertaken with two main aims. Firstly, to evaluate the adverse effects of hyperoxia on the ciliary coverage using a novel large animal model. For the first time, an in vitro bronchus bovine tissue culture model was developed and used to quantify ciliary coverage loss over time. The protection role of antioxidant supplementation with α-tocopherol and ascorbate was also investigated. Secondly, the importance of the tight junction protein ZO-1 in hyperoxia-induced monolayer permeability was investigated using a human bronchial cell line (16HBE14o-) and the potential inflammation effects on bronchial tightness. Additionally studies were carried out in order to find out if antioxidant vitamin treatment can protect against or reduce these effects. Scanning electronic microscopy indicated that hyperoxia caused a time dependent decline (t½ = 3.4 d compared to 37.1 d under normoxia) in ciliary coverage (P < 0.0001). This was associated with an increase in the number of sloughed cells, many apparently intact, into the medium (p < 0.05). Several biochemical parameters were assessed to obtain evidence of oxidative stress caused by hyperoxia in this model including tissue damage (lactate dehydrogenase, LDH, in the medium), lipid peroxidation (thiobarbituric acid reactive substances, TBARS), DNA damage (comet assay used for the first time with primary bronchus culture), protein oxidation (OxyBlot kit) and antioxidant status (total glutathione). Antioxidant vitamins had a significant protective effect on the hyperoxia-induced reduction in percentage ciliary coverage (P < 0.05). Moreover, an increase in the bronchial permeability was shown characterised by a significant decrease (P < 0.05) in transepithelial electrical resistance (TER) under hyperoxic conditions. The reduction of ZO-1 associated fluorescence (P < 0.01) is in compatible with the downregulation of ZO-1 expression assessed by RT-PCR. Levels of the pro-inflammatory cytokines IL-8, IL-6 and TNF-a concentration in the medium, as measured by ELISA, increased significantly (P < 0.001) under hyperoxia, and this was accompanied with a marked increase in the cytokine expression. However, the antioxidant vitamins E and C, partially reduced the impact effects of hyperoxia, both individually and in combination, whilst increases in ZO-1 expression and fluorescence intensity (P < 0.05), as well as the suppression of cytokine secretion and gene expression was modest. Use of these vitamins was not enough to reduce the epithelial permeability significantly compared to normoxia. The data implies that hyperoxia-induced damage to cultured bovine bronchial epithelium and the denudation of cilia over time with increased permeability was due, at least in part, to the decline in TJ protein expression and associated fluorescence intensity. The antioxidant vitamins vitamin E and C had partial protective effects against hyperoxia damage. However, additional studies are called for in order to further understand the possible associations between oxidative stress and inflammation caused by hyperoxia and tight junction proteins, also response to treatment with antioxidant individually or in combination.

Diss. (sammanfattning) Linköping : Linköpings universitet, 2007. / Härtill 4 uppsatser.

PURPOSE: Normobaric hyperoxia (NBH) has been shown in animal models of experimental retinal detachment (RD) to effectively prevent photoreceptor degeneration. Furthermore, choroidal hyperpermeability has been implicated in the disease pathophysiology. In this study, we studied the effects of 3-hours of 40% FIO2 NBH on photoreceptor morphology and visual acuity in patients with vision loss associated with active central serous chorioretinopathy (CSCR). MATERIALS and METHODS: A total of 8 patients with active unilateral CSCR received at least one 3-hour NBH (40% FIO2) session. Best corrected visual acuity (BCVA) as well as thickness of the central macula, subretinal fluid (SRF), photoreceptor layer (PL), and outer nuclear layer (ONL) were assessed. RESULTS: In patients with unilateral acute CSCR, 3 hours of 40% FIO2 NBH showed a trend towards improved vision, but no statistical differences were obtained for BCVA, CMT, SRF, PL, or ONL. CONCLUSIONS: Administration of 3-hours of NBH did not induce any measurable anatomic changes in the retina nor any significant changes in visual acuity. These results challenge the hypothesis of choroidal hyperpermeability in CSCR and suggest that additional or alternative pathologies contribute to this disease. / 2022-11-29T00:00:00Z

Coral reef ecosystems are under increasing threat from ocean warming and deoxygenation. Mass coral bleaching events in recent years have been linked to marine heatwaves but reporting of hypoxia-induced bleaching has also been increasing. Oxygen availability in coral reefs is driven by community metabolism and they experience a dynamic range of oxygen concentrations throughout diel cycles, hyperoxia during the day and hypoxia during the night. It has been suggested that the highest oxygen concentrations coincide with the hottest part of the day and this may protect marine taxa from high temperatures. We evaluated experimentally whether excess oxygen availability would increase the thermal threshold of the branching coral Stylophora pistillata, from the Southern Red Sea. We did this by exposing coral fragments of this species to varying dissolved oxygen concentrations (hypoxia, normoxia and hyperoxia) and a short-term temperature ramping regime (1˚C h-1). Hyperoxia did extend the thermal tolerance of S. pistillata fragments, with an LT50 of 39.1˚C as opposed to 39.0˚C for the normoxic treatment and 38.7˚C for the hypoxic treatment. Hyperoxia also increased respiration and gross photosynthesis and had a negative effect on photochemical efficiency at high temperatures. Net photosynthesis, P:R ratio and symbiont density were not significantly affected by oxygen concentration. Corals in this experiment displayed exceedingly high thermal thresholds, which were at least 2˚C higher than previously reported for the same species in the Central Red Sea. The corals used in the experiment had previously survived mass bleaching events in 2015 and hence we may have selected for individuals adapted to thermal stress. This is the first study to investigate the role of oxygen in the thermal tolerance of hermatypic corals and the first assessment of thermal thresholds from corals in the Southern Red Sea, where previously thermal thresholds have been based on a 1-2˚C increase in maximum mean monthly temperatures and visual bleaching observations. This highlights the need for increased experimental assessments of thermal thresholds in the Southern regions of the Red Sea and the important role of oxygen in moderating thermal stress.

PURPOSE: Ischemic retinopathies such as diabetic retinopathy (DR), retinal vein occlusions (RVO), and age-related macular degeneration (AMD) are ocular diseases caused by abnormal changes in the microvasculature that results in ischemia. This is often followed by a secondary phase characterized by pathological neovascularization and leakage of fluid, which contributes to a loss of visual acuity in affected patients. Anti-VEGF therapy, the current standard of treatment for ischemic retinopathies, is invasive, costly, and lacks a known treatment period. Supplemental oxygen provides the therapeutic potential of not only oxygenating hypoxic retinal cells, but also reducing the neovascularization and edema associated with many ischemic retinopathies through the downregulation of proangiogenic and pro-inflammatory cytokines.The objective of this study is to understand the biochemical underpinnings of treating ischemic retinopathies with hyperoxia. The elucidation of the effect hyperoxia on the molecular level may help guide the development of future studies regarding this novel treatment. METHODS: 68 undiluted vitreous samples were obtained during pars plana vitrectomy (PPV) and the concentration analysis of 34 proteins was analyzed using the Bio-Plex Pro Human Cancer Biomarker Assay. Vitreous samples were divided into three groups: (1) eyes of patients who underwent PPV for epiretinal membrane peeling (ERMP) and/or macular hole (MH) with no history of diabetes mellitus (non-DM group); (2) eyes of patients who underwent PPV for ERMP and/or MH with a history of diabetes or nonproliferative diabetic retinopathy (DM group); (3) eyes of patients who underwent PPV for proliferative diabetic retinopathy (PDR group). Mann-Whitney U tests were performed to compare the biomarker concentrations between the three groups. RESULTS: Numerous growth factors and inflammatory cytokines were significantly upregulated between the non-DM and PDR groups - Angiopoietin-2, EGF, Endoglin, G-CSF, HB-EGF, HGF, PDGF, PIGF, sHER2/neu, TIE-2, VEGF-A, VEGF-D, IL-18, IL-6, IL-8, PECAM-1, sCD40L, SCF, sFASL, sIL-6Ra, TNF-⍺, Leptin, PAI-1, and uPA. A literature search of these proteins revealed many to be directly activated by HIF-1 transcription factor, which is the "master switch" for genes transcribed during a hypoxic event. CONCLUSION: The abundance of proangiogenic and pro-inflammatory factors in PDR that are also upregulated by HIF-1 demonstrate the potential for using hypoxia to treat PDR (and other ischemic retinopathies) through the reduction of HIF-1. This study also shows the wide variability in the expression levels of these proteins which helps provide a better understanding of their degree of involvement in the pathogenesis of ischemic retinopathies. / 2021-06-14T00:00:00Z