Effect of Short-Term Intermittent Normobaric Hypoxia on the Regulation of External Respiration in Humans

Baseline external respiration and gas exchange values, as well as ventilatory thresholds and sensitivity to the O₂ and CO₂ stimuli in hypoxic and hypercapnic tests, were measured 1 h before and after a session of intermittent normobaric hypoxia (INH) (six repetitions with a 5-min inhalation of a gas mixture (10% O₂) alternating with a 3-min inhalation of atmospheric air). After an INH session, the background CO₂ level in the lungs increased by 10%. In the hypercapnic test, the actuation threshold of the ventilatory response did not change, whereas ventilatory sensitivity increased. The maximal pulmonary ventilation and the corresponding critical CO₂ level in the lungs also increased at the end of the test. In the hypoxic test, the ventilatory response occurred at a decreased level of blood oxygenation after an INH session, the pulmonary ventilation level being decreased and the CO₂ content in the lungs being increased at the end of the test. The data obtained evidence the maintenance of changed gas homeostasis for 1 h after an INH session. In this process, control of respiration was effected, with the hypoxic drive being weakened and the peripheral chemoreceptor sensitivity being decreased. The hypercapnic drive also increased, which may be determined by readjustment in the central mechanisms of respiratory regulation.     

Intermittent Normobaric Hypoxia as a Model of Incomplete Adaptation

The Neirokartograf software was used to calculate the correlations between EEG, external respiration, and gas exchange parameters recorded in the initial state, after 10 or 20 sessions of intermittent normobaric hypoxia (INH), and after its cessation. It was demonstrated that cerebral structures were increasingly involved in gas exchange control in ascending order during the course of INH sessions. The artificial short-term extreme exposure followed by a return to usual conditions resulted in incomplete adaptation. Even 20 days after the cessation of INH sessions, neurodynamics did not return to the initial state.     

Regulation of External Respiration and Gas Exchange during a 20-Day Exposure to Sessions of Intermittent Normobaric Hypoxia

A study was made of the effects of a 20-day course of intermittent normobaric hypoxia (INH) on the parameters of gas exchange and the regulation of respiration in healthy volunteers. A phasic change in oxygen consumption at rest was observed: it decreased on the 10th day of the INH course and increased on the 20th day, with a parallel increase in the efficiency of pulmonary ventilation. According to the hypercapnic test, the ventilatory response threshold decreased, whereas ventilatory sensitivity increased; these effects were most pronounced during the first ten days of INH training and still detectable in recovery. It was assumed that the first phase of training (up to the tenth day) is associated with compensatory activation of pulmonary ventilation owing to an increase in peripheral and central chemosensitivity to the CO₂ stimulus. In the second phase, which was associated with further slight changes in the parameters of external respiration, the gas exchange level is restored owing to an adaptive increase in efficiency of oxygen utilization in cells and tissues.     

A Four-Way Comparison of Cardiac Function with Normobaric Normoxia,Normobaric Hypoxia,Hypobaric Hypoxia and Genuine High Altitude

BackgroundThere has been considerable debate as to whether different modalities of simulated hypoxia induce similar cardiac responses.ResultsAll 14 subjects completed the experiment at GHA, 11 at NN, 12 under NH, and 6 under HH. The four groups were similar in age, sex and baseline demographics. At baseline rest right ventricular (RV) systolic pressure (RVSP, p = 0.0002), pulmonary vascular resistance (p = 0.0002) and acute mountain sickness (AMS) scores were higher and the SpO₂ lower (p<0.0001) among all three hypoxic groups (GHA, NH and HH) compared with NN. At both 15 minutes and 120 minutes post exercise, AMS scores, Cardiac output, septal S’, lateral S’, tricuspid S’ and A’ velocities and RVSP were higher and SpO₂ lower with all forms of hypoxia compared with NN. On post-test analysis, among the three hypoxia groups, SpO₂ was lower at baseline and 15 minutes post exercise with GHA (89.3±3.4% and 89.3±2.2%) and HH (89.0±3.1 and (89.8±5.0) compared with NH (92.9±1.7 and 93.6±2.5%). The RV Myocardial Performance (Tei) Index and RVSP were significantly higher with HH than NH at 15 and 120 minutes post exercise respectively and tricuspid A’ was higher with GHA compared with NH at 15 minutes post exercise.ConclusionsGHA, NH and HH produce similar cardiac adaptations over short duration rest despite lower SpO₂ levels with GHA and HH compared with NH. Notable differences emerge following exercise in SpO_2, RVSP and RV cardiac function.     

Morphological and Functional Changes in Overweight Persons under Combined Normobaric Hypoxia and Physical Training

Functional and morphological changes were studied in overweight persons in tests with various combinations of normobaric hypoxia and physical training. It was shown that normobaric hypoxia combined with training can be used for increasing physical working capacity and aerobic capacity in overweight persons. A combination of physical training and breathing hypoxic gas mixtures was demonstrated to be the most effective method of correcting and increasing the physiological functional potential in overweight persons.     

Regional Blood Flow in the Upper Extremity during and after Exposure to Acute Normobaric Hypoxia

Cardiovascular indices were analyzed in young healthy males exposed to normobaric hypoxia (breathing a gas mixture containing 10% O₂ for 16 min). There was a marked variation in individual responses. A linear relationship was observed between the individual blood oxygen saturation at the end of exposure and the baseline muscle blood flow (MBF). Moreover, blood oxygen saturation decreased in subjects with an initially high forearm MBF and remained unchanged or even slightly increased in subjects with a low forearm MBF. After hypoxic exposure (10–15 min), the MBF continued to decrease, venous capacity increased, and postocclusion hyperemic response decreased. It is suggested that hypoxic exposure activates the neuroreflex mechanisms regulating the peripheral blood flow and that the peripheral vascular response to acute hypoxia depends largely on the baseline blood flow in skeletal muscles.     

Adaptation to Intermittent Hypoxia: Influence on the State of Endothelial Function

Human Physiology - This study involving ten apparently healthy male volunteers aged 19 to 31 years was aimed at establishing possible effects of a three-week course of normobaric intermittent...     

Intermittent Hypercapnic Hypoxia Induced Protein Changes in the Piglet Hippocampus Identified by MALDI-TOF-MS

Intermittent hypercapnic hypoxia (IHH) induces protein changes in the brainstem, but its effects on the hippocampus have not yet been studied. Using a proteomics-based approach, we tested the hypothesis that IHH up-regulates apoptotic promoters and down-regulates apoptotic inhibitors in the developing hippocampus. Male piglets aged 13–14 days were assigned to control (n = 6) or IHH (n = 5) groups. Using two-dimensional polyacrylamide gel electrophoresis, matrix-assisted laser desorption/ionisation-time of flight-mass spectrometry (MALDI-TOF-MS), a total of 26 protein spots were differentially expressed in IHH compared to control group. Thirteen of these (6 up-regulated, 7 down-regulated) were identified including 14-3-3θ/τ (increased), glial fibrillary acidic protein (increased) and α-internexin (decreased). Further analysis with western blot validated these proteins and immunohistochemistry showed specific regional changes in the subiculum, stratum radiatum and CA1 of the hippocampus. Most proteins identified were involved in promoting cell survival under apoptotic conditions. These findings improve our understanding of the cellular processes that occur in the hippocampus during IHH exposure, and have important implications in clinical settings where IHH is experienced, for example, during prone sleeping or with obstructive sleep apnea in an infant.     

Role of Nitric Oxide Synthase in the Infarct-Limiting Effect of Normobaric Hypoxia

Journal of Evolutionary Biochemistry and Physiology - The study was carried out in male Wistar rats. Animals were randomly divided into normoxic control groups and groups exposed to normobaric...     

Role of Glutamate in the Mechanisms of Adaptation of the System of Respiratory Control in Rats to Intermittent Hypoxia

In experiments on Wistar rats, we studied the role of changes in the state of glutamatergic transmission in the course of adaptation of the system of respiratory control to intermittent hypoxia. The volume/temporal parameters of respiration were estimated according to characteristics of EMG activity (amplitude, integral intensity of EMG discharges) recorded from the diaphragmatic muscle. Changes in EMG activity of the diaphragm induced by acute hypoxia (breathing a 12% О₂-containing gas mixture) were estimated before and after of a 14-day-long course of intermittent hypoxia trainings and before and after inductions of a blocker of NMDA receptors, МK-801. The results prove that the glutamatergic transmitter system is significantly involved in the reaction of the respiratory system to presentation of a hypoxic stimulus within all stages of formation of the ventilatory response, both before and after the action of intermittent hypoxia. Blocking of NMDA receptors under conditions of adaptation to intermittent hypoxia exerted a more intense influence on the amplitude of respiratory EMG discharges of the diaphragm than on their frequency.     

Autophagy-Associated Atrophy and Metabolic Remodeling of the Mouse Diaphragm after Short-Term Intermittent Hypoxia

Background

Short-term intermittent hypoxia (IH) is common in patients with acute respiratory disorders. Although prolonged exposure to hypoxia induces atrophy and increased fatigability of skeletal muscle, the response to short-term IH is less well known. We hypothesized that the diaphragm and limb muscles would adapt differently to short-term IH given that hypoxia stimulates ventilation and triggers a superimposed exercise stimulus in the diaphragm.

Methods

We determined the structural, metabolic, and contractile properties of the mouse diaphragm after 4 days of IH (8 hours per day, 30 episodes per hour to a FiO2 nadir=6%), and compared responses in the diaphragm to a commonly studied reference limb muscle, the tibialis anterior. Outcome measures included muscle fiber size, assays of muscle proteolysis (calpain, ubiquitin-proteasome, and autophagy pathways), markers of oxidative stress and mitochondrial function, quantification of intramyocellular lipid and lipid metabolism genes, type I myosin heavy chain (MyHC) expression, and in vitro contractile properties.

Results

After 4 days of IH, the diaphragm alone demonstrated significant atrophy (30% decrease of myofiber size) together with increased LC3B-II protein (2.4-fold) and mRNA markers of the autophagy pathway (LC3B, Gabarapl1, Bnip3), whereas active calpain and E3 ubiquitin ligases (MuRF1, atrogin-1) were unaffected in both muscles. Succinate dehydrogenase activity was significantly reduced by IH in both muscles. However, only the diaphragm exhibited increased intramyocellular lipid droplets (2.5-fold) after IH, along with upregulation of genes linked to activated lipid metabolism. In addition, although the diaphragm showed evidence for acute fatigue immediately following IH, it underwent an adaptive fiber type switch toward slow type I MyHC-expressing fibers, associated with greater intrinsic endurance of the muscle during repetitive stimulation in vitro.

Conclusions

Short-term IH induces preferential atrophy in the mouse diaphragm together with increased autophagy and a rapid compensatory metabolic adaptation associated with enhanced fatigue resistance.     

Diaphragm Muscle Remodeling in a Rat Model of Chronic Intermittent Hypoxia

Respiratory muscle remodeling occurs in human sleep apnea—a common respiratory disorder characterized by chronic intermittent hypoxia (CIH) due to recurrent apnea during sleep. We sought to determine if CIH causes remodeling in rat sternohyoid (upper airway dilator) and diaphragm muscles. Adult male Wistar rats were exposed to CIH (n=8), consisting of 90 sec of hypoxia (5% at the nadir; SaO₂ ~80%)/90 sec of normoxia, 8 hr per day, for 7 consecutive days. Sham animals (n=8) were exposed to alternating air/air cycles in parallel. The effect of CIH on myosin heavy-chain (MHC) isoform (1, 2a, 2x, 2b) distribution, sarcoplasmic reticulum calcium ATPase (SERCA) isoform distribution, succinate dehydrogenase activity, glycerol phosphate dehydrogenase activity, and Na⁺/K⁺ ATPase pump content was determined. Sternohyoid muscle structure was unaffected by CIH treatment. CIH did not alter oxidative/glycolytic capacity or the Na⁺/K⁺-ATPase pump content of the diaphragm. CIH significantly increased the areal density of MHC 2b fibers in the rat diaphragm, and this was associated with a shift in SERCA proteins from SERCA2 to SERCA1. We conclude that CIH causes a slow-to-fast fiber transition in the rat diaphragm after just 7 days of treatment. Respiratory muscle functional remodeling may drive aberrant functional plasticity such as decreased muscle endurance, which is a feature of human sleep apnea.     

Respiratory Function and Changes in Lung Epithelium Biomarkers after a Short-Training Intervention in Chlorinated vs. Ozone Indoor Pools

Background

Swimming in indoor pools treated with combined chemical treatments (e.g. ozone) may reduce direct exposure to disinfection byproducts and thus have less negative effects on respiratory function compared to chlorinated pools. The aim of this study is to analyze the effects of a short-term training intervention on respiratory function and lung epithelial damage in adults exercising in indoor swimming pool waters treated with different disinfection methods (chlorine vs. ozone with bromine).

Methods

Lung permeability biomakers [surfactant protein D (SP-D) and Clara cell secretory protein (CC16) in plasma] and forced expiratory volumes and flow (FEV1, FVC and FEF_25–75) were measured in 39 healthy adults. Thirteen participants swam during 20 sessions in a chlorinated pool (CP), 13 performed and equivolumic intervention in an ozone pool (OP) and 13 were included in a control group (CG) without exposition.

Results

Median plasma CC16 levels increased in CP swimmers (4.27±3.29 and 6.62±5.51 µg/L, p = 0.01, pre and post intervention respectively) while no significant changes in OP and CG participants were found. No significant changes in median plasma SP-D levels were found in any of the groups after the training period. FVC increased in OP (4.26±0.86 and 4.43±0.92 L, p<0.01) and CP swimmers (4.25±0.86 and 4.35±0.85 L, p<0.01). FEV1 only increased in OP swimmers (3.50±0.65 and 3.59±0.67, p = 0.02) and FEF_25–75 decreased in CP swimmers (3.70±0.87 and 3.37±0.67, p = 0.02).

Conclusion

Despite lung function being similar in both groups, a higher lung permeability in CP compared to OP swimmers was found after a short-term swimming program. Combined chemical treatments for swimming pools such as ozone seem to have less impact on lung epithelial of swimmers compared to chlorinated treated pools.     

The pH-Sensitive Potassium Channel TASK-1 Is a Chemosensor for Central Respiratory Regulation in Rats

Molecular Biology - TWIK-related acid-sensitive potassium channel-1 (TASK-1) is a “leak” potassium channel sensitive to extracellular protons. It contributes to setting the resting...     

Activation of Respiratory Chain Complex II as a Hypoxia Tolerance Indicator during Acute Hypoxia

Activation of respiratory chain complex II during acute hypoxia is an adaptive response that facilitates electron transfer in the respiratory chain when complex I is blocked. Stress induced by acute oxygen deficiency in the body stimulates epinephrine and norepinephrine release into the bloodstream. As a result, compensatory metabolic flows and succinate dehydrogenase and succinate oxidation are activated in the cell. Succinate dehydrogenase activation associated with acute hypoxia exhibits characteristic fluctuations; moreover, stronger stimulation results in oscillations with a shorter period and a higher amplitude. These fluctuations are a consequence of the reciprocal relationship between the sympathetic and parasympathetic systems. In subjects who developed adaptation to hypoxia following repeated sessions of breathing a hypoxic gas mixture, no activation of the succinate–ubiquinone-reductase shunt under hypoxic load was observed. The blood lymphocyte reaction can serve as an indicator of tolerance to acute hypoxia.     

Expression of Erythropoietin mRNA in the Brainstem of Rats Adapted to Intermittent Hypoxia

We studied the content of mRNA of a glycoprotein, erythropoietin, in structures of the rat brainstem; the animals were adapted to intermittent hypoxia at different contents of oxygen in hypoxic gas mixtures (12 or 7% О₂, a 2-week-long course with five sessions per day). Under conditions of such adaptation, the content of erythropoietin in the brainstem demonstrated a clear trend toward a decrease after a course of moderate hypoxic trainings (12% О₂), and a more than twofold drop after a “stronger” course (7% О₂). We suppose that the decrease in the intensity of synthesis of this glycoprotein