Rainbow trout (Oncorhynchus mykiss) exposed to oxygen supersaturation and handling stress: plasma cortisol and hepatic glutathione status

Three groups of one summer old rainbow trout were exposed for 22 days either to normoxia (100%) or moderate oxygen supersaturation; 120% and 140%. After the exposure, all groups were transported for three hours in hyperoxic conditions (123% O2) thus simultaneously experiencing density and handling stress. The recovery of rainbow trout to multiple stressors was measured in normoxic conditions. Moderate oxygen supersaturation did not have any negative effects on growth, feed conversion and blood hematology measured over 22 days. On the other hand, the combined effects of the stressful environment in the fish farm and oxygen supersaturation resulted in a 3-fold increase in plasma cortisol levels in those with 100% and 120% O2 supersaturation and a 2-fold increase in the 140% supersaturation group. Furthermore, the stress response after transportation was lowest in the 140% group 24 hours after recovery but highest after 70 hours. Moderate hyperoxia or transportation stress did not change glutathione concentrations in liver indicating that routine sampling does not affect hepatic glutathione status. Our results indicate that moderate O2 supersaturation (<140%) could be considered as feasible in cultivation of rainbow trout since no harmful effects were found.     

The effect of oxygen on the growth of Oncorhynchus mykiss embryos with and without a chorion

Growth was measured in dechorionated and chorionated embryos of rainbow trout Oncorhynchus mykiss exposed to three oxygen treatments: hypoxia, normoxia and hyperoxia (nominally 5, 10 and 15 mg l⁻¹). Dechorionated embryos grew faster than chorionated ones in all three oxygen treatments. Similar patterns, however, were found in both dechorionated and chorionated groups; embryos exposed to hypoxia grew less than normoxic and hyperoxic exposed embryos. Moreover, there was no significant interaction between the effect of oxygen levels and presence or absence of the chorion on growth after hatching. These results suggest that the effect of oxygen on growth was not affected by the presence of the chorion.     

Responses of type II pneumocyte antioxidant enzymes to normoxic and hyperoxic culture

Summary Cultured type II pneumocyte responses to in vitro normoxia (95% air: 5% CO₂) or hyperoxia (95% O₂:5% CO₂) were quantified. Normoxic culture (0 to 96 h) of rabbit type II cells resulted in enhanced cell-monolayer protein and DNA content. During this same time, cellular activities of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH Px) decreased. Compared to cultures maintained in normoxia, hyperoxic exposure of cultures resulted in decreased cell-associated protein and DNA content. Exposure to hyperoxia also resulted in cytotoxicity as demonstrated by elevated cellular release of DNA, lactate dehydrogenase (LDH), and preincorporated 8-[¹⁴C]adenine. Cellular catalase and GSH Px activities in hyperoxic cells decreased similarly to normoxic controls. In contrast, cellular SOD activity in hyperoxic cells decreased less than in normoxic cultures. Cellular SOD activity in hyperoxic cultures, when normalized for cellular protein, but not DNA, was greater than normoxic values after 24 to 96 h of exposure. Unlike the decrease in cellular antioxidant enzymes during normoxic and hyperoxic culture, cellular LDH activity increased during both these exposures. Cellular LDH activity in 24 to 96 h hyperoxia-exposed cells increased to a lesser extent than normoxic controls. The extent of depression in LDH activity was dependent on whether the activity was normalized for cellular protein or DNA. Type II pneumocytes, which normally undergo hyperplasia and hypertrophy during hyperoxia in vivo, exhibited oxygen sensitivity in vitro. Exposure of type II cells to hyperoxia in vitro resulted in alterations in cellular SOD and LDH activities, but recognition of such changes were dependent on whether enzymatic activities were normalized for cellular DNA or protein. This work was supported by a grant from the Health Effects Institute, grant HL40458 from the National Institutes of Health, Bethesda, MD, and a grant from the American Lung Association, New York, NY.     

Hyperoxia enhances metaboreflex sensitivity during static exercise in humans

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 Sa(O2) 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.     

Nucleotides and the adenylate energy charge as indicators of stress in rainbow trout (Oncorhynchus mykiss) subjected to a range of dissolved oxygen concentrations

Liver nucleotides (ATP, ADP, AMP, IMP), the adenylate energy charge (AEC), total adenylate concentration (TA), and IMP-load were used as measures of stress in rainbow trout (Oncorhynchus mykiss) acclimated to normoxic (10.0 mg/l), hypoxic (6.5 mg/l), and supersaturated (13.0 mg/l) dissolved oxygen concentrations and subjected to a challenge by confinement. Liver ATP (783.0 nmol/g) was significantly different in the normoxic fish compared to either hyperoxic (447.7 nmol/g) or hypoxic (402.0 nmol/g) fish at the end of the confinement. Within 6.0 hr in the confinement, liver AEC in the normoxic fish increased significantly (0.58) compared to hypoxic (0.42) and hyperoxic fish (0.42). Similarly, the IMP-load in normoxic fish (0.16) decreased to near prestress levels by 6.0 hr in confinement compared to either the hypoxic (0.31) or hyperoxic (0.30) fish. Nucleotides in liver were significantly affected by the dissolved oxygen treatments and the confinement stress in contrast to the muscle nucleotides which were not.     

GM-CSF and the impaired pulmonary innate immune response following hyperoxic stress

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.     

Hyperoxia results in transient oxidative stress and an adaptive response by antioxidant enzymes in goldfish tissues

The effects of hyperoxia on the status of antioxidant defenses and markers of oxidative damage were evaluated in goldfish tissues. The levels of lipid peroxides, thiobarbituric acid reactive substances, carbonyl proteins and the activities of some antioxidant enzymes were measured in brain, liver, kidney and skeletal muscle of goldfish, Carassius auratus L., over a time course of 3-12 h of hyperoxia exposure followed by 12 or 36 h of normoxic recovery. Exposure to high oxygen resulted in an accumulation of protein carbonyls in tissues throughout hyperoxia and recovery whereas lipid peroxides and thiobarbituric acid reactive substances accumulated transiently under short-term hyperoxia stress (3-6 h) but were then strongly reduced. This suggests that hyperoxia stimulated an enhancement of defenses against lipid peroxidation or mechanisms for enhancing the catabolism of peroxidation products. The activities of principal antioxidant enzymes, superoxide dismutase and catalase, were not altered under hyperoxia but catalase increased during normoxic recovery; activities may rise in anticipation of further hyperoxic excursions. In most tissues, the activities of glutathione-utilizing enzymes (glutathione peroxidase, glutathione-S-transferase, glutathione reductase) as well as glucose-6-phosphate dehydrogenase, were not affected under hyperoxia but increased sharply during normoxic recovery. Correlations between some enzyme activities and oxidative stress markers were found, for example, an inverse correlation was seen between levels of thiobarbituric acid reactive substances and glutathione-S-transferase activity in liver and catalase and glucose-6-phosphate dehydrogenase in kidney. The results suggest that liver glutathione-S-transferase plays an important role in detoxifying end products of lipid peroxidation accumulated under hyperoxia stress.     

Hyperbaric hyperoxia reduces exercising forearm blood flow in humans

Hypoxia during exercise augments blood flow in active muscles to maintain the delivery of O(2) at normoxic levels. However, the impact of hyperoxia on skeletal muscle blood flow during exercise is not completely understood. Therefore, we tested the hypothesis that the hyperemic response to forearm exercise during hyperbaric hyperoxia would be blunted compared with exercise during normoxia. Seven subjects (6 men/1 woman; 25 ± 1 yr) performed forearm exercise (20% of maximum) under normoxic and hyperoxic conditions. Forearm blood flow (FBF; in ml/min) was measured using Doppler ultrasound. Forearm vascular conductance (FVC; in ml·min(-1)·100 mmHg(-1)) was calculated from FBF and blood pressure (in mmHg; brachial arterial catheter). Studies were performed in a hyperbaric chamber with the subjects supine at 1 atmospheres absolute (ATA) (sea level) while breathing normoxic gas [21% O(2), 1 ATA; inspired Po(2) (Pi(O(2))) ≈ 150 mmHg] and at 2.82 ATA while breathing hyperbaric normoxic (7.4% O(2), 2.82 ATA, Pi(O(2)) ≈ 150 mmHg) and hyperoxic (100% O(2), 2.82 ATA, Pi(O(2)) ≈ 2,100 mmHg) gas. Resting FBF and FVC were less during hyperbaric hyperoxia compared with hyperbaric normoxia (P < 0.05). The change in FBF and FVC (Δ from rest) during exercise under normoxia (204 ± 29 ml/min and 229 ± 37 ml·min(-1)·100 mmHg(-1), respectively) and hyperbaric normoxia (203 ± 28 ml/min and 217 ± 35 ml·min(-1)·100 mmHg(-1), respectively) did not differ (P = 0.66-0.99). However, the ΔFBF (166 ± 21 ml/min) and ΔFVC (163 ± 23 ml·min(-1)·100 mmHg(-1)) during hyperbaric hyperoxia were substantially attenuated compared with other conditions (P < 0.01). Our data suggest that exercise hyperemia in skeletal muscle is highly dependent on oxygen availability during hyperoxia.     

Oxidative stress decreases antioxidant enzyme activities in reaggregation cultures of rat brain cells

The brain has been suggested to be especially sensitive to damage by reactive oxygen species. In this study, we examined the effects of hyperoxic conditions on the activities and mRNA levels of antioxidant enzymes in reaggregation cultures of rat forebrain cells. Cultures were exposed to 80% oxygen for 12–60 h starting on Days 17 and 33 in culture. Superoxide dismutase activities and mRNA levels were not affected by hyperoxia, whereas catalase activity was slightly decreased after 24 h in 80% oxygen at Day 17. Glutathione peroxidase activity was markedly decreased already after 12 h of hyperoxia, and decreased activities of glutathione reductase and glucose-6-phosphate dehydrogenase were also noted. The glutathione peroxidase mRNA levels were increased in hyperoxic cultures at Day 17 but not at Day 33. These results suggest that the enzymatic defense mechanisms against reactive oxygen species in the brain are rather weak and deteriorate during oxidative stress but that a potential for compensatory upregulation exists at least during the first postnatal weeks.     

Attenuation of lipopolysaccharide-induced oxidative stress and apoptosis in fetal pulmonary artery endothelial cells by hypoxia

Pulmonary vascular endothelial injury resulting from lipopolysaccharide (LPS) and oxygen toxicity contributes to vascular simplification seen in the lungs of premature infants with bronchopulmonary dysplasia. Whether the severity of endotoxin-induced endothelial injury is modulated by ambient oxygen tension (hypoxic intrauterine environment vs. hyperoxic postnatal environment) remains unknown. We posited that ovine fetal pulmonary artery endothelial cells (FPAEC) will be more resistant to LPS toxicity under hypoxic conditions (20–25 Torr) mimicking the fetal milieu. LPS (10 μg/ml) inhibited FPAEC proliferation and induced apoptosis under normoxic conditions (21% O₂) in vitro. LPS-induced FPAEC apoptosis was attenuated in hypoxia (5% O₂) and exacerbated by hyperoxia (55% O₂). LPS increased intracellular superoxide formation, as measured by 2-hydroxyethidium (2-HE) formation, in FPAEC in normoxia and hypoxia. 2-HE formation in LPS-treated FPAEC increased in parallel with the severity of LPS-induced apoptosis in FPAEC, increasing from hypoxia to normoxia to hyperoxia. Differences in LPS-induced apoptosis between hypoxia and normoxia were abolished when LPS-treated FPAEC incubated in hypoxia were pretreated with menadione to increase superoxide production. Apocynin decreased 2-HE formation, and attenuated LPS-induced FPAEC apoptosis under normoxic conditions. We conclude that ambient oxygen concentration modulates the severity of LPS-mediated injury in FPAEC by regulating superoxide levels produced in response to LPS.     

Zinc content of the gills of rainbow trout (S. gairdneri) after treatment with zinc solutions under normoxic and hypoxic conditions

Forty specimens of rainbow trout (54–127 g) were divided into 4 groups which were treated as follows: (a) normoxic clean water; (b) hypoxic clean water; (c) normoxic water with 10 ppm zinc for 10 h; (d) hypoxic water with 10 ppm zinc for 10 h. The zinc content was determined separately for each of the 4 gill arches on each side of the fish. Values for the zinc concentration were greater following the zinc treatments, but no significant difference between hypoxia and normoxia was observed. Differences in concentrations of zinc were found in different arches whether expressed per gram dry weight or per unit surface area of the secondary lamellae.     

Physiological stress effects of continuous- and pulsed-DC electroshock on juvenile bull trout

Juvenile bull trout Salvelinus confluentus exposed to continuous- or pulsed-DC electroshock exhibited rapid elevations in plasma cortisol and glucose, but plasma chloride did not change. In a 1-h experiment using 240 V at 1·4 A of 60-Hz pulsed DC (voltage gradient 0·81 V cm⁻¹), which proved lethal, plasma cortisol and glucose rose significantly within 15 min of a 10-s electroshock. Plasma cortisol reached a peak level of 156 ± 18 ng ml⁻¹ at 45 min and then decreased, whereas plasma glucose reached its highest level of 179 ± 7·5mg dl⁻¹ at 1 h. In a 24-h experiment using lower dosages, plasma cortisol increased from 6·1-16 ng ml⁻¹ to peak levels of 155–161 ng ml⁻¹ in 1 h in response to a 10-s electroshock of continuous (130 V, 0·5 A, 1·45 V cm⁻¹) or pulsed (120 V, 0·5 A, 60 Hz, 0·55 V cm⁻¹) DC. Although plasma concentrations declined thereafter, levels remained above control values at 24 h. Plasma glucose was elevated from 60–65 to 120–134 mg dl⁻¹ after 1h by both electroshock treatments and remained near or above those levels for the 24-h duration. Plasma cortisol and glucose levels were much higher in electroshocked bull trout at 1 h compared with those in fish 1 h after receiving a 30-s handling stressor (cortisol, 90 ± 12 ng ml⁻¹; glucose, 82 ± 6·1 mg dl⁻¹). The results indicate that both continuous and pulsed DC were more stressful to juvenile bull trout than handling and that recovery, at least for pulsed DC, may take longer than 24 h.     

Effects of sodium valproate and oxygen on the CD-1 mouse fetus

This study reports the effects of valproic acid (VA) on the CD-1 mouse fetus when the drug is administered continuously via osmotic minipumps at human therapeutic drug plasma levels. Two VA-filled Alzet osmotic minipumps were implanted subcutaneously on gestation day 5 for continuous exposure of a total daily dosage of 850 mg/kg on gestation days 5-12. Dams were then exposed continuously to either normoxic (21% oxygen), hyperoxic (50% oxygen), or hypoxic (12% oxygen) controlled environments during gestation days 5-12, in order to determine if hyperoxic maternal conditions offered a protective environment for the fetus, and conversely, if hypoxia exacerbated teratogenicity. Dams were sacrificed on gestation day 18, and litter and fetal data were collected. It was determined in separate groups under normoxic conditions that the osmotic minipump system maintained VA plasma levels corresponding to human therapeutic levels. Sodium valproate was found to induce developmental toxicity in the CD-1 mouse fetus at human therapeutic drug plasma levels. Fetal weights were reduced, and the number of resorptions, deaths, and hematomas was increased. While hypoxia exacerbated the toxic effect on the fetus, hyperoxia failed to ameliorate the outcome.     

Changes in haematocrit values in blood samples treated with and without oxygen: a comparative study with four salmonid species

Changes in haematocrit values under lowered oxygen tension and aerobically treated blood samples of rainbow trout Salmo gairdneri (Richardson), landlocked Baltic salmon S. salar (L.), brown trout S. trutta lacustris (L.) and lake trout Salvelinus namaycush (Walbaum) have been studied in vitro . The mean haematocrit value increased during 2 h incubation under lowered oxygen tension by 32.7 ± 3.1% in rainbow trout, 28.2 ± 2.8% in landlocked Baltic salmon, 29.2 ± 5.6% in brown trout and 25.2 ± 2.8% in lake trout. During corresponding incubation with oxygen the mean haematocrit value decreased below the starting level by 18.1 ± 1.9% in rainbow trout, 18.3 ± 4.8% in landlocked Baltic salmon, 22.4 ± 0.7% in brown trout and 11.8 ± 1.7% in lake trout. Consequently, the changes in the haematocrit values were greater in the species belonging to the genus Salmo than in that of the genus Salvelinus . The increase in the haematocrit values seems to have resulted from swelling of the erythrocytes and their decrease is similarly attributable to shrinking of the cells. The reasons for this swelling, which may be complicated, and its apparent significance for haematocrit determinations are discussed.     

rIL‐10 enhances IL‐10 signalling proteins in foetal alveolar type II cells exposed to hyperoxia

Although the mechanisms by which hyperoxia promotes bronchopulmonary dysplasia are not fully defined, the inability to maintain optimal interleukin (IL)‐10 levels in response to injury secondary to hyperoxia seems to play an important role. We previously defined that hyperoxia decreased IL‐10 production and pre‐treatment with recombinant IL‐10 (rIL‐10) protected these cells from injury. The objectives of these studies were to investigate the responses of IL‐10 receptors (IL‐10Rs) and IL‐10 signalling proteins (IL‐10SPs) in hyperoxic foetal alveolar type II cells (FATIICs) with and without rIL‐10. FATIICs were isolated on embryonic day 19 and exposed to 65%‐oxygen for 24 hrs. Cells in room air were used as controls. IL‐10Rs protein and mRNA were analysed by ELISA and qRT‐PCR, respectively. IL‐10SPs were assessed by Western blot using phospho‐specific antibodies. IL‐10Rs protein and mRNA increased significantly in FATIICs during hyperoxia, but JAK1 and TYK2 phosphorylation showed the opposite pattern. To evaluate the impact of IL‐8 (shown previously to be increased) and the role of IL‐10Rs, IL‐10SPs were reanalysed in IL‐8‐added normoxic cells and in the IL‐10Rs’ siRNA‐treated hyperoxic cells. The IL‐10Rs’ siRNA‐treated hyperoxic cells and IL‐8‐added normoxic cells showed the same pattern in IL10SPs with the hyproxic cells. And pre‐treatment with rIL‐10 prior to hyperoxia exposure increased phosphorylated IL‐10SPs, compared to the rIL‐10‐untreated hyperoxic cells. These studies suggest that JAK1 and TYK2 were significantly suppressed during hyperoxia, where IL‐8 may play a role, and rIL‐10 may have an effect on reverting the suppressed JAK1 and TYK2 in FATIICs exposed to hyperoxia.     

Detrimental cerebrometabolic effects of hyperoxia in newborn rats

To investigate the pathogenesis of oxygen toxicity in the newborn brain, we exposed one-day-old Sprague-Dawley albino rats to 100% O₂ and measured whole-brain high-energy phosphates, glucose, lactate, and free fatty acids (FFA) after 0, 15, 30, 60 and 120 min. Whole-brain adenosine triphosphate and creatine phosphate fell significantly from about 4.5 to 2.5 μmol-mg⁻¹ protein. Brain lactate remained at about 0.3 μmol·mg⁻¹ protein in hyperoxic rats, but increased in normoxic rats, from 0.3 to 1.3 μmol·mg⁻¹ protein at 120 min. Total FFA decreased from 30 to 15 nmol·mg⁻¹ protein during normoxia, but increased to 40 nmol·mg⁻¹ protein during hyperoxia. Undetectable in normoxic rats, arachidonic acid increased to between 4 and 6 nmol·mg⁻¹ protein during hyperoxia while oleic acid increased by two to threefold. In normoxia, palmitate decreased by 70% from 12 to 4 nmol·mg⁻¹ protein whereas in hyperoxia it remained at 10 nmol·mg⁻¹ protein. Normobaric 100% O₂ has detrimental metabolic effects on the neonatal brain which cannot be attributed to cerebral vasospasm or seizure-induced cerebral anoxia because lactic acidosis was not observed. FFA changes suggest that a likely explanation is membrane lipid peroxidation from O₂-induced free radicals.     

Effect of acute hypoxia on respiratory muscle fatigue in healthy humans

Background

Greater diaphragm fatigue has been reported after hypoxic versus normoxic exercise, but whether this is due to increased ventilation and therefore work of breathing or reduced blood oxygenation per se remains unclear. Hence, we assessed the effect of different blood oxygenation level on isolated hyperpnoea-induced inspiratory and expiratory muscle fatigue.

Methods

Twelve healthy males performed three 15-min isocapnic hyperpnoea tests (85% of maximum voluntary ventilation with controlled breathing pattern) in normoxic, hypoxic (SpO₂ = 80%) and hyperoxic (FiO₂ = 0.60) conditions, in a random order. Before, immediately after and 30 min after hyperpnoea, transdiaphragmatic pressure (P_di,tw ) was measured during cervical magnetic stimulation to assess diaphragm contractility, and gastric pressure (P_ga,tw ) was measured during thoracic magnetic stimulation to assess abdominal muscle contractility. Two-way analysis of variance (time x condition) was used to compare hyperpnoea-induced respiratory muscle fatigue between conditions.

Results

Hypoxia enhanced hyperpnoea-induced P_di,tw and P_ga,tw reductions both immediately after hyperpnoea (P_di,tw : normoxia -22 ± 7% vs hypoxia -34 ± 8% vs hyperoxia -21 ± 8%; P_ga,tw : normoxia -17 ± 7% vs hypoxia -26 ± 10% vs hyperoxia -16 ± 11%; all P < 0.05) and after 30 min of recovery (P_di,tw : normoxia -10 ± 7% vs hypoxia -16 ± 8% vs hyperoxia -8 ± 7%; P_ga,tw : normoxia -13 ± 6% vs hypoxia -21 ± 9% vs hyperoxia -12 ± 12%; all P < 0.05). No significant difference in P_di,tw or P_ga,tw reductions was observed between normoxic and hyperoxic conditions. Also, heart rate and blood lactate concentration during hyperpnoea were higher in hypoxia compared to normoxia and hyperoxia.

Conclusions

These results demonstrate that hypoxia exacerbates both diaphragm and abdominal muscle fatigability. These results emphasize the potential role of respiratory muscle fatigue in exercise performance limitation under conditions coupling increased work of breathing and reduced O₂ transport as during exercise in altitude or in hypoxemic patients.     

Postnatal development of the denervated lung in normoxia, hypoxia, or hyperoxia.

We asked whether lung innervation was essential for the normal postnatal development of the lung in conditions of normoxia, hypoxia, or hyperoxia. Litters of newborn rats were assigned to a normoxic [inspired oxygen partial pressure (PIO2) = 150 Torr, eight litters], hypoxic (PIO2 = 100 Torr, nine litters), or hyperoxic (PIO2 = 360 Torr, nine litters) group. Each litter consisted of 12 pups. Two days after birth, one-third of the litter had the vagus and sympathetic trunk cut in the neck on the left side [left denervated (L)], one-third was denervated on the right side (R), and one-third was sham-operated (S). From day 3, all pups were exposed to the designed PIO2, until day 8 or days 21-22. Almost all rats, whether S, R, or L, survived in normoxia and hyperoxia, whereas in hypoxia survival at day 22 of R and L was approximately 60-65%. Body growth was the same in S, R, and L and less in hypoxia than in normoxia or hyperoxia. At days 8 and 22, hematocrit and hemoglobin concentration, heart and lung dry and wet weights, and lung DNA content did not differ among S, R, and L, whether the pups were raised in normoxia, hypoxia, or hyperoxia. At days 21-22, aerobic metabolism and breathing pattern, both measured during air breathing, as well as compliance of isolated lungs, were also similar among S, R, and L for each of the conditions in which the pups were raised.(ABSTRACT TRUNCATED AT 250 WORDS)