Hypoxia Recovery Research Articles

Effects of Different Protocols of Moderate-Intensity Intermittent Hypoxic Training on Mental Health and Quality of Life in Brazilian Adults Recovered from COVID-19: The AEROBICOVID Double-Blind Randomized Controlled Study

The aim of this study was to investigate the effects of different protocols of moderate-intensity intermittent hypoxic training in patients who had recovered from COVID-19 on quality of life (QoL) and mental health. The sample of this clinical trial-controlled double-blind study consisted of 67 participants aged 30–69 years, who were organized randomly according to Normoxia, Hypoxia, Hypoxia Recovery or Control Group. Eight weeks of cycle ergometer training were performed with a frequency of three training sessions per week in normoxic or hypoxic conditions (with or without hypoxic recovery). Health-related QoL and Mental Health Status were evaluated by 12-Item Short Form Survey and Depression Anxiety and Stress Scale instruments, respectively. All training groups improved the QoL’s physical dimensions (Baseline–Post: Normoxia Group 42.1 (11.0)–48.7 (7.0), Hypoxia Group 46.9 (11.8)–53.5 (6.6) and Hypoxia Recovery Group 45.8 (9.2)–51.1 (5.3)) and mental dimensions (Baseline–Post: Normoxia Group 48.8 (7.9)–54.6 (4.6), Hypoxia Group 45.2 (7.7)–53.2 (3.8) and Hypoxia Recovery Group 46.5 (9.7)–52.0 (9.9)). Regarding mental health outcomes, all training groups decreased depressive symptoms (66.7% Normoxia, 31.2% Hypoxia Recovery and 31% Hypoxia groups), anxiety symptoms (46.5% Normoxia, 45.9% Hypoxia Recovery and 39.5% in the Hypoxia groups) and stress symptoms (40.6% Normoxia, 36.3% Hypoxia Recovery and 22.1% Hypoxia groups). Significant statistical difference was not found between groups. Normoxic and hypoxic training showed a similar effect on QoL and the mental health of Brazilian adults who had recovered from COVID-19.

Comparisons Between Normobaric Normoxic and Hypoxic Recovery on Post-exercise Hemodynamics After Sprint Interval Cycling in Hypoxia.

The aim of this study was to investigate the effects of either normoxic or hypoxic recovery condition on post-exercise hemodynamics after sprint interval leg cycling exercise rather than hemodynamics during exercise. The participants performed five sets of leg cycling with a maximal effort (30 s exercise for each set) with a 4-min recovery of unloaded cycling between the sets in hypoxia [fraction of inspired oxygen (FiO2) = 0.145]. The load during pedaling corresponded to 7.5% of the individual’s body weight at the first set, and it gradually reduced from 6.5 to 5.5%, 4.5, and 3.5% for the second to fifth sets. After exercise, the participants rested in a sitting position for 30 min under normoxia (room-air) or hypoxia. Mean arterial pressure decreased over time during recovery (p < 0.001) with no condition and interaction effects (p > 0.05). Compared to pre-exercise values, at 30 min after exercise, mean arterial pressure decreased by 5.6 ± 4.8 mmHg (mean ± standard deviation) during hypoxic recovery, and by 5.3 ± 4.6 mmHg during normoxic recovery. Peripheral arterial oxygen saturation (SpO2) at all time points (5, 10, 20, and 30 min) during hypoxic recovery was lower than during normoxic recovery (all p < 0.05). The area under the hyperemic curve of tissue oxygen saturation (StO2) at vastus lateralis defined as reperfusion curve above the baseline values during hypoxic recovery was lower than during normoxic recovery (p < 0.05). Collectively, post-exercise hypotension after sprint interval leg cycling exercise was not affected by either normoxic or hypoxic recovery despite marked differences in SpO2 and StO2 during recovery between the two conditions.

Dynamic labelling reveals central carbon metabolism responses to stepwise decreasing hypoxia and reoxygenation during postharvest in pear fruit

Storage of pears in low oxygen conditions after harvest and before commercialization induces several responses in their metabolism initiating survival, maintenance and low energy expenditure mechanisms. In the present study a metabolomics approach was used in combination with a 13C feeding experiment to elucidate those metabolic responses in pear fruit under a stepwise induced hypoxic profile by monitoring changes in TCA, fermentation, GABA shunt associated metabolites and amino acids. A reoxygenation treatment was added at the end of the experiment to study the post hypoxic recovery mechanisms after prolonged hypoxia. Propagation of label through metabolic pathways was monitored by GC–MS analysis. Results showed successful utilization of 13C pyruvate from pear tissue under normoxia accompanied by fractional enrichment in organic acids, pyruvate and TCA cycle derived amino acids. Initiation of hypoxia at 5 kPa O2 resulted in drop of fractional enrichment in malate, fumarate, citrate, valine, glutamate and alanine but not in α-ketoglutarate and succinate. Further induction of severe hypoxia (0.5 kPa O2) resulted in a decrease of the TCA cycle activity, initiation of fermentation and primary evidence of an upregulated alanine-α-ketoglutarate shunt, a trend that continued until the 0.2 kPa O2 incubation. Sucrose and fructose decreased below 0.5 kPa O2 with a sharp increase of phosphorylated sugars that dropped by the end of the treatment. Reoxygenation caused upregulation of the TCA cycle but not glycolysis, reversed fermentation activity and a drop in concentration of all amino acids. Results were in line with common responses of plants under hypoxia and post anoxia recovery mechanisms and suggest that different mechanisms are implemented between normoxia and reoxygenation after prolonged hypoxia.

Astrocytes are involved in the maintenance of respiratory augmentation in the post hypoxic recovery phase

Astrocytes are involved in the maintenance of respiratory augmentation in the post hypoxic recovery phase

Effects of Hypobaric and Normobaric Hypoxia on Myogenic and Proteolytic Gene Expression in Humans

Muscle mass is reduced during extended exposure to a hypoxic environment. Current research suggests that the physiological response to normobaric and hypobaric hypoxia may be different. It is currently unknown if these previously described differences extend to the skeletal muscle and transcriptional response regulating muscle mass. PURPOSE: To determine the effects of normobaric and hypobaric hypoxia on myogenenic and proteolytic gene expression. METHODS: Recreationally trained subjects (n = 15; age = 24 ± 4 y; VO2max = 3.60 ± 0.83 L · min-1) completed three trials of 60-min cycling at 70% of Wmax followed by 4-h of recovery at ambient control conditions (975 m), normobaric hypoxia (4,420 m), and hypobaric hypoxia (4,420 m). For each trial, a muscle biopsy was taken from the vastus lateralis before exercise and at the end of the 4-h recovery period for analysis of gene expression (RT-qPCR). RESULTS: There were no differences in the myogenic gene expression of MYOD (p = 0.713), MYF-5 (0.053), or MYOG (0.832) between trials. MYF-6 was higher after exercise (p = 0.002) regardless of trial. MSTN decreased from pre- to post-exercise (p < 0.001) in all conditions and was lower in hypobaric hypoxia compared to control condition (p = 0.02) and normobaric condition (p = 0.037). There were no differences in the proteolytic gene expression of atrogin-1 with exercise (p =0.811) or between trials (p = 0.419). However, FOXO3 (p = 0.009) and MuRF-1 (p < 0.001) gene expression increased with exercise but were not different between conditions (p = 0.543, p = 0.327, respectively). CONCLUSION: These data indicate that hypoxic recovery from exercise, regardless of whether normobaric or hypobaric, does not affect the expression of genes related to myogenesis and proteolysis with the exception of a modest attenuation of myostatin in hypobaric hypoxia. Funding provided by the Department of Defense United States Army Medical Research and Materiel Command (DOD USAMRMC: W81XWH-15-2-0075).

Bone marrow-derived mesenchymal stem cells ameliorate sodium nitrite-induced hypoxic brain injury in a rat model.

Sodium nitrite (NaNO2) is an inorganic salt used broadly in chemical industry. NaNO2 is highly reactive with hemoglobin causing hypoxia. Mesenchymal stem cells (MSCs) are capable of differentiating into a variety of tissue specific cells and MSC therapy is a potential method for improving brain functions. This work aims to investigate the possible therapeutic role of bone marrow-derived MSCs against NaNO2 induced hypoxic brain injury. Rats were divided into control group (treated for 3 or 6 weeks), hypoxic (HP) group (subcutaneous injection of 35 mg/kg NaNO2 for 3 weeks to induce hypoxic brain injury), HP recovery groups N-2wR and N-3wR (treated with the same dose of NaNO2 for 2 and 3 weeks respectively, followed by 4-week or 3-week self-recovery respectively), and MSCs treated groups N-2wSC and N-3wSC (treated with the same dose of NaNO2 for 2 and 3 weeks respectively, followed by one injection of 2 × 106 MSCs via the tail vein in combination with 4 week self-recovery or intravenous injection of NaNO2 for 1 week in combination with 3 week self-recovery). The levels of neurotransmitters (norepinephrine, dopamine, serotonin), energy substances (adenosine monophosphate, adenosine diphosphate, adenosine triphosphate), and oxidative stress markers (malondialdehyde, nitric oxide, 8-hydroxy-2′-deoxyguanosine, glutathione reduced form, and oxidized glutathione) in the frontal cortex and midbrain were measured using high performance liquid chromatography. At the same time, hematoxylin-eosin staining was performed to observe the pathological change of the injured brain tissue. Compared with HP group, pathological change of brain tissue was milder, the levels of malondialdehyde, nitric oxide, oxidized glutathione, 8-hydroxy-2′-deoxyguanosine, norepinephrine, serotonin, glutathione reduced form, and adenosine triphosphate in the frontal cortex and midbrain were significantly decreased, and glutathione reduced form/oxidized glutathione and adenosine monophosphate/adenosine triphosphate ratio were significantly increased in the MSCs treated groups. These findings suggest that bone marrow-derived MSCs exhibit neuroprotective effects against NaNO2-induced hypoxic brain injury through exerting anti-oxidative effects and providing energy to the brain.

Does Hyperoxic Recovery during Cross-country Skiing Team Sprints Enhance Performance?

This study aimed to determine the acute responses of breathing oxygen-enriched air during the recovery periods of a simulated 3 × 3-min cross-country skiing team sprint competition at simulated low altitude. Eight well-trained male endurance athletes performed two 3 × 3-min team sprint simulations on a double-poling ergometer at simulated altitude set at ∼ 1800 m. During the recovery periods between the 3 × 3-min sprints, all the athletes inhaled either hyperoxic (FiO2 = 1.00) or hypoxic (FiO2 ∼ 0.165) air in randomized and single-blind order. The mean total power output (P(mean tot)) and the mean power output of each sprint (P(mean) 1,2,3) were determined. Perceived exertion, capillary oxygen saturation of hemoglobin, partial pressure of oxygen, and blood lactate concentration were measured before and after all the sprints. No differences in P(mean tot) were found between hyperoxic (198.4 ± 27.1 W) and hypoxic (200.2 ± 28.0 W) recovery (P = 0.57, effect size [d] = 0.07). P(mean) 1,2,3 (P > 0.90, d = 0.04-0.09) and RPE (P > 0.13, d = 0.02-0.63) did not differ between hyperoxic and hypoxic recovery. The partial pressure of oxygen (P < 0.01, d = 0.06-5.45) and oxygen saturation (P < 0.01, d = 0.15-5.40) during hyperoxic recovery were higher than those during hypoxic recovery. The blood lactate concentration was also lower directly after the third sprint (P = 0.03, d = 0.54) with hyperoxic recovery. Results indicate that trained endurance athletes who inhale 100% oxygen during recovery periods in a cross-country skiing team sprint at low altitude do not exhibit enhanced performance despite the improvement in the key physiological variables of endurance performance.

Influence of post-exercise hypoxic exposure on hepcidin response in athletes

To assess the influence of a simulated altitude exposure (~2,900 m above sea level) for a 3 h recovery period following intense interval running on post-exercise inflammation, serum iron, ferritin, erythropoietin, and hepcidin response. In a cross-over design, ten well-trained male endurance athletes completed two 8 × 3 min interval running sessions at 85 % of their maximal aerobic velocity on a motorized treadmill, before being randomly assigned to either a hypoxic (HYP: F IO2 ~0.1513) or a normoxic (NORM: F IO2 0.2093) 3 h recovery period. Venous blood was collected pre- and immediately post-exercise, and after 3 and 24 h of recovery. Blood was analyzed for interleukin-6, serum iron, ferritin, erythropoietin, and hepcidin. Interleukin-6 was significantly elevated (p < 0.01) immediately post-exercise compared to baseline (NORM: 1.08 ± 0.061 to 3.12 ± 1.80) (HYP: 1.32 ± 0.86 to 2.99 ± 2.02), but was not different between conditions. Hepcidin levels were significantly elevated (p < 0.01) at 3 h post-exercise for both conditions when compared to baseline (NORM: 3.25 ± 1.23 to 7.40 ± 4.00) (HYP: 3.24 ± 1.94 to 5.42 ± 3.20), but were significantly lower (p < 0.05) in the HYP trial compared to NORM. No significant differences existed between HYP and NORM for erythropoietin, serum iron, or ferritin. Simulated altitude exposure (~2,900 m) for 3 h following intense interval running attenuates the peak hepcidin levels recorded at 3 h post-exercise. Consequently, a hypoxic recovery after exercise may be useful for athletes with compromised iron status to potentially increase acute dietary iron absorption.

Exercise-induced oxidative stress and hypoxic exercise recovery

Hypoxia due to altitude diminishes performance and alters exercise oxidative stress responses. While oxidative stress and exercise are well studied, the independent impact of hypoxia on exercise recovery remains unknown. Accordingly, we investigated hypoxic recovery effects on post-exercise oxidative stress. Physically active males (n = 12) performed normoxic cycle ergometer exercise consisting of ten high:low intensity intervals, 20 min at moderate intensity, and 6 h recovery at 975 m (normoxic) or simulated 5,000 m (hypoxic chamber) in a randomized counter-balanced cross-over design. Oxygen saturation was monitored via finger pulse oximetry. Blood plasma obtained pre- (Pre), post- (Post), 2 h post- (2Hr), 4 h post- (4Hr), and 6 h (6Hr) post-exercise was assayed for Ferric Reducing Ability of Plasma (FRAP), Trolox Equivalent Antioxidant Capacity (TEAC), Lipid Hydroperoxides (LOOH), and Protein Carbonyls (PC). Biopsies from the vastus lateralis obtained Pre and 6Hr were analyzed by real-time PCR quantify expression of Heme oxygenase 1 (HMOX1), Superoxide Dismutase 2 (SOD2), and Nuclear factor (euthyroid-derived2)-like factor (NFE2L2). PCs were not altered between trials, but a time effect (13 % Post-2Hr increase, p = 0.044) indicated exercise-induced blood oxidative stress. Plasma LOOH revealed only a time effect (p = 0.041), including a 120 % Post-4Hr increase. TEAC values were elevated in normoxic recovery versus hypoxic recovery. FRAP values were higher 6Hr (p = 0.045) in normoxic versus hypoxic recovery. Exercise elevated gene expression of NFE2L2 (20 % increase, p = 0.001) and SOD2 (42 % increase, p = 0.003), but hypoxic recovery abolished this response. Data indicate that recovery in a hypoxic environment, independent of exercise, may alter exercise adaptations to oxidative stress and metabolism.

822 Hypoxic Recovery Following Massive Small Bowel Resection as Measured by Photoacoustic Microscopy

822 Hypoxic Recovery Following Massive Small Bowel Resection as Measured by Photoacoustic Microscopy

Opioid μ‐receptors in the rostral medullary raphe modulate hypoxia‐induced hyperpnea in unanesthetized rats

It has been suggested that the medullary raphe (MR) plays a key role in the physiological responses to hypoxia. As the rostral MR (rMR) expresses an extensive population of opioid μ‐receptors, we studied the putative role of opioid μ‐receptors in the rMR region on ventilation in normal and 7% hypoxic conditions. We measured pulmonary ventilation and the body temperatures of male Wistar rats before and after the selective opioid μ‐receptor antagonist CTAP (D‐Phe‐Cys‐Tyr‐D‐Trp‐Arg‐Thr‐Pen‐Thr‐NH2, cyclic, 0.1 μg/0.1 μL) was microinjected into the rMR during normoxia or after 60 minutes of hypoxia. The animals treated with intra‐rMR CTAP exhibited an attenuation of the ventilatory response to hypoxia (430 ± 86 mL kg−1 min−1) compared to the control group (790 ± 82 mL kg−1 min−1) (P&lt;0.05) due to a reduced tidal volume (3.0 ± 0.41 versus 6.1 ± 0.6 ml kg−1; P&lt;0.05). During hypoxic recovery, the ventilation remained reduced in the CTAP intra‐rRM group. No differences in the Tb were observed among groups during hypoxia. These data suggest that opioids acting on μ‐receptors in the rMR exert an excitatory modulation of hyperventilation induced by hypoxia.Financial support: FAPESP, CNPq, PRONEX.

Erythropoietin and its antagonist regulate the hypoxic fictive breathing in newborn mice

Erythropoietin (Epo) in adult mouse interacts with the major brainstem centers associated with respiration to enhance the ventilatory response to acute and chronic conditions of physiological hypoxia (e.g. as occuring at high altitude). However, whether Epo is as well implicated in the regulation of breathing in newborns remains unknown. To answer this question en bloc brainstem‐spinal cord preparations were obtained from mice at postnatal day 4 (P4). After time‐ (30, 60 or 90 min) and dose‐dependent (0, 25 or 250 U) incubation with or without Epo, en bloc preparations were superfused with artificial cerebrospinal fluid (aCSF) bubbled with normoxic or hypoxic gas mixtures. Subsequently, the electrophysiological fictive breathing produced by axons at the C4 ventral root was recorded. Our results show that upon hypoxic conditions Epo stimulates the neural hypoxic respiratory activity and improves the post hypoxic recovery. In addition, proof‐of‐concept experiments showed that soluble Epo receptor (sEpoR), the endogenous antagonist of Epo, dramatically decreases the neural hypoxic respiratory activity. These results imply that Epo and its endogenous antagonist in P4 mice are implicated in the modulation and maintenance of respiratory motor output during hypoxic and post‐hypoxic challenges. As Epo is a highly promising protective therapeutic agent for several brain diseases, these results suggest that Epo applications may be also relevant for neuronal‐related respiratory disorders in term and preterm neonates.

Effect of Acute Hypoxia on the Motor Activity and Heart Rate of the 10- and 14-Day Chick Embryo

Embryonic motility is an important component of development and may be a precursor of posthatching motor behavior. In chickens, it accompanies almost the entire embryogenesis and depends on environmental conditions, whose effects on embryonic motility have been poorly studied. The effect of acute hypoxia (10% O 2 for 10 min) on the temporal parameters of chick embryo motility on incubation days 10 (D10) and 14 (D14) was estimated; the results were compared with data on the heart rate (HR). A force transducer connected with an embryo limb was used to record embryonic movements simultaneously with HR video recording. In the control, the duration of the activity phase (APh) and HR increased, while the inactivity phase (IPh) decreased in the period from D10 to D14. In response to hypoxia, the APh did not change significantly on either day, but the IPh significantly increased on D14 and tended to increase on D10. A distinct pattern of the motor activity response to hypoxia was observed on D14: the IPh increased after 0.5-2.5 min of hypoxia, peaked at a value 6 times as large as the control one, and then partly recovered. Under hypoxia, the mean HR significantly decreased to 87% of the control value and then partly recovered, increasing to 93% on both days studied. The similarity of the hypoxic patterns of IPh and HR on D14 suggests that the hypoxic recovery of HR contributes to the recovery of the embryo motility under hypoxia in late embryos.

Effect Of Oxygen Concentration On Glucose Tolerance And Cortisol Level During Postexercise Recovery

PURPOSE: The current study compared glucose tolerance (OGTT), insulin response, lower limb blood flow, and stress hormone level on 3 different oxygen concentrations following exercise. METHODS: 8 healthy male subjects performed an exhaustive exercise, were recovered for 100 min under normoxic (21% O2), hypoxic (14% O2), and hyperoxic (60% O2) conditions. RESULTS: Glucose, cortisol, and lower limb blood flow under hypoxia recovery condition were significantly greater than that under normoxic and hypoxic recovery conditions. Glucose and cortisol levels under hyperoxic recovery condition were significantly lower than under normoxic condition. CONCLUSIONS: High oxygen delivery provided the best result in post-exercise glucose tolerance, and this appears to be related to the lower stress hormone level.

β-Adrenergic Receptor Stimulation and Adenoviral Overexpression of Superoxide Dismutase Prevent the Hypoxia-mediated Decrease in Na,K-ATPase and Alveolar Fluid Reabsorption

Hypoxia has been shown to cause lung edema and impair lung edema clearance. In the present study, we exposed isolated rat lungs to pO(2) = 40 mm Hg for 60 min or rats to 8% O(2) for up to 24 h and then measured changes in alveolar fluid reabsorption (AFR) and Na,K-ATPase function. Low levels of oxygen severely impaired AFR in both ex vivo and in vivo models. The decrease in AFR was associated with a decrease in Na,K-ATPase activity and protein abundance in the basolateral membranes from peripheral lung tissue of hypoxic rats. Beta-adrenergic agonists restored AFR in rats exposed to 8% O(2) (from 0.02 +/- 0.07 ml/h to 0.59 +/- 0.03 ml/h), which was associated with parallel increases in Na,K-ATPase protein abundance in the basolateral membrane. Hypoxia is associated with increased production of reactive oxygen species. Therefore, we examined whether overexpression of SOD2, manganese superoxide dismutase, would prevent the hypoxia-mediated decrease in AFR. Spontaneously breathing rats were infected with a replication-deficient human type 5 adenovirus containing cDNA for SOD2. An otherwise identical virus that contained no cDNA was used as a control (Adnull). Hypoxic Adnull rats had decreased rates of AFR (0.12 +/- 0.1 ml/h) as compared with hypoxic AdSOD2 and normoxic control rats (0.47 +/- 0.04 ml/h and 0.49 +/- 0.02 ml/h, respectively), with parallel changes in Na,K-ATPase.

Energy state, pH, and vasomotor tone during hypoxia in precontracted pulmonary and femoral arteries.

To assess effects of smooth muscle energy state and intracellular pH (pH(i)) on pulmonary arterial tone during hypoxia, we measured ATP, phosphocreatine, P(i), and pH(i) by (31)P-NMR spectroscopy and isometric tension in phenylephrine-contracted rings of porcine proximal intrapulmonary arteries. Hypoxia caused early transient contraction followed by relaxation and late sustained contraction. Energy state and pH(i) decreased during relaxation and recovered toward control values during late contraction. Femoral arterial rings had higher energy state and lower pH(i) under baseline conditions and did not exhibit late contraction or recovery of energy state and pH(i) during hypoxia. In pulmonary arteries, glucose-free conditions abolished late hypoxic contraction and recovery of energy state and pH(i), but endothelial denudation abolished only late hypoxic contraction. NaCN had little effect at 0. 1 and 1.0 mM but caused marked vasorelaxation and decreases in energy state and pH(i) at 10 mM. These results suggest that 1) regulation of tone, energy state, and pH(i) differed markedly in pulmonary and femoral arterial smooth muscle, 2) hypoxic relaxation was mediated by decreased energy state or pH(i) due to hypoxic inhibition of oxidative phosphorylation, 3) recovery of energy state and pH(i) in hypoxic pulmonary arteries was due to accelerated glycolysis mediated by mechanisms intrinsic to smooth muscle, and 4) late hypoxic contraction in pulmonary arteries was mediated by endothelial factors that required hypoxic recovery of energy state and pH(i) for transduction in smooth muscle or extracellular glucose for production and release by endothelium.

Susceptibility of isolated rat facial nerve to anaerobic stress.

Ischemic lesions are presumed to be part of many facial nerve pathologies, such as Bell's palsy. The response of facial nerve to hypoxia has not been evaluated previously in an in vitro model. In the present study, the effects of transient anaerobic stress on functional parameters and their recovery were assessed. Extratemporal rat facial nerves were desheathed and incubated in an experimental chamber using solutions containing either low (5 mM) or high (25 mM) D-glucose. In some of the experiments, 40 microM phenytoin or lidocaine was added to observe the effects of membrane stabilizing drugs. Peak height of compound nerve action potential (CNAP), extracellular direct current (DC) potential and latency were measured simultaneously during and after a 40-min period of hypoxia, induced by bubbling the solutions with N2 or application of 3 mM cyanide. This resulted in a rapid decrease of CNAP and a depolarization of the DC potential with a fast and complete post hypoxic recovery. Elevated glucose concentrations led to a slower decline in CNAP and a smaller rise of membrane potential depolarization. This was accompanied by a slower change of latency. However, post-anaerobic recovery was always diminished in the high glucose solutions. In experiments with phenytoin or lidocaine longer impulse conduction during hypoxia was observed. These findings indicate that the availability of energy-rich components underlies the complex array of physiological derangements seen in ischemia. Membrane-stabilizing drugs show an effect on signal conduction during hypoxia and need further exploration.

Hypoxia induced metabolism dysfunction of rat astrocytes in primary cell cultures

In order to study the astroglial contribution to hypoxic injury on brain tissue metabolism, modifications of glutamine synthetase (GS) lactate dehydrogenase (LDH) enolase and malate dehydrogenase activity produced by reduced oxygen supply have been determined in primary cultures of astrocytes prepared from newborn rat cerebral cortex. Enzymatic activities were measured immediately after the hypoxic treatment (9 h) and during post injury recovery. GS level is significantly decreased in response to low oxygen pressure and increased above control value during the post hypoxic recovery period. The magnitude of GS reduction by hypoxia depends on the age of the cells in culture. Lactate dehydrogenase and enolase levels were significantly enhanced during the two periods considered. No modification of the MDH level was observed. The synthesis of LDH isoenzymes containing mainly M subunits is specifically induced by hypoxia. Our results suggest that astroglial cells may represent a particularly sensitive target toward hypoxia injury in brain tissue. Low oxygen pressure available may modify some fundamental metabolical functions of these cells such as glutamate turnover and lactic acid accumulation.

A comparative study of octopine dehydrogenase isoenzymes in gastropod, bivalve and cephalopod molluscs

Abstract 1. 1. Activities of octopine dehydrogenase (ODH) and lactate dehydrogenase (LDH) were assayed in the muscular and non-muscular tissues of one gastropod (Baccinum undatum), three bivalves (Mytilus edulis, Cardium tuberculatum, Pecten jacobaeus) and one cephalopod (Loligo vulgaris) mollusc. 2. 2. In the gastropod and bivalve molluscs two bands always stained for ODH activity after polyacrylamide electrophoresis; no electrophoretic differences were found between different tissues of the same species. Furthermore, the kinetic properties of purified ODH from M. edulis and B. undatum showed no essential differences between tissues of the same species. The data suggest that octopine formation and re-oxidation could take place without the need for transportation between tissues. 3. 3. Preparation of ODH from the optic lobe and mantle tissue of L. vulgaris differ in elution behavior on Blue Sepharose and in electrophoretic mobility. 4. 4. Kinetic studies suggest that optic lobe ODH is analogous to vertebrate H-type LDH and mantle muscle ODH resembles vertebrate muscle-type LDH; for example, optic lobe ODH is strongly substrate inhibited by pyruvate and octopine and more product (octopine) inhibited than the muscle form. Optic lobe ODH forms an inhibitory quaternary complex (enzyme-pyruvate-arginine-NAD+), analogous to the abortive ternary complex of H-type LDH. Finally, the optic lobe ODH has a higher affinity for octopine and NAD+ than muscle ODH. 5. 5. Increased levels of octopine in the mantle muscle, blood and optic lobe after exhaustive swimming and hypoxic recovery support the view that octopine is produced in the mantle via the reaction of the muscle isoenzyme and is subsequently flushed out into the blood and transported to other tissues, such as the optic lobe, for re-oxidation via the optic lobe isoenzyme.