Intermittent Normobaric Hypoxia Research Articles

Interleukins expression by lymphocytes of rats exposed to chronic intermittent normobaric hypoxia

Hypoxia acute and chronic modulates the expression of inflammatory mediators such as cytokines. However, studies in chronic and intermittent hypobaric or normobaric hypoxia similar to described in miner’s population are scares o absent. In regards with this we propose evaluated the effect of chronic intermittent normobaric hypoxia (CINH) on the hematological, cardiovascular response and expression of lymphocyte’s cytokines such as IL-1b, IL-2, IL6 and IL-10 in rats. A total of 20 Sprague-Dawley rats were divided in two groups: a) CINH of FiO2 10% (n=10) and normoxic rats (n=10) were used as controls. Blood samples were obtained from both groups for hematological studies, systolic arterial pressure and heart rate was measured in tail-cuff sensor, and expression of cytokines obtained from lymphocytes was determined by RT-PCR. Hematocrit, hemoglobin, platelet count and hematological constant are elevated however leucocyte count decrease. A significant increase of systolic arterial pressure (over 50%). In vitro expression of cytokines from lymphocytes shown that IL-10, IL-2 and IL6 increase 35%, 64% and 16% respectively, while that of IL-1bdecreases by 18%. CINH could be activate an inflammatory response mediated by IL-2, however this response could be attenuated due to the increase in the expression of IL-10, a known anti-inflammatory cytokine, and the decrease in the expression of IL-1β and IL6 suggesting a mechanism of adaptation to CINH. Innova-Corfo Project 07CN13ISM-152. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Hypoxia matters: comparison of external and internal training load markers during an 8-week resistance training program in normoxia, normobaric hypoxia and hypobaric hypoxia.

To compare external and internal training load markers during resistance training (RT) in normoxia (N), intermittent hypobaric hypoxia (HH), and intermittent normobaric hypoxia (NH). Thirty-three volunteers were assigned an 8-week RT program in either N (690m, n = 10), HH (2320m, n = 10), or NH (inspired fraction of oxygen = 15.9%; ~ 2320m, n = 13). The RT program (3x/week) consisted of six exercises, with three sets of six to 12 repetitions at ~ 70% of one repetition maximum (1RM) with the first session of each week used for analysis. 1RM in back squat and bench press was used to evaluate muscle strength before and after the program. External load was assessed by the volume load relative to body mass (RVL, kg·kg-1). Internal load was assessed by the ratings of perceived exertion (RPE) and heart rate (HR). Smaller relative improvements were found for the back squat in the N group (11.5 ± 8.8%) when compared to the NH group (22.2 ± 8.2%, P = 0.01) and the HH group (22 ± 8.1%, P = 0.02). All groups showed similar RVL, HR responses and RPE across the program (P˃0.05). However, reduced HR recovery values, calculated as the difference between the highest HR value (HRpeak) and the resting heart rate after a two min rest, were seen in the N and NH groups across the program (P 0.05). It seems that 8weeks of intermittent RT in hypoxic environments could maximize time-efficiency when aiming to improve strength levels in back squat without evoking higher levels of physiological stress. Performing RT at hypobaric hypoxia may improve the cardiorespiratory response, which in turn could speed recovery.

Intermittent normobaric hypoxia therapy for COVID-19 survivors: a promising approach to recovery

This groundbreaking study delves into the transformative potential of Intermittent Normobaric Hypoxia Therapy (INHT) in a targeted cohort of 50 young adult COVID-19 survivors, aged 18 to 24 years. Through comprehensive pre- and post-INHT spirometry assessments, our research uncovers the nuanced respiratory benefits of this innovative therapy. The results showcase significant improvements in key spirometry parameters, emphasizing INHT's pivotal role in restoring lung function and fostering holistic respiratory well-being post-COVID-19

Intermittent normobaric hypoxia alters substrate partitioning and muscle oxygenation in individuals with obesity: implications for fat burning.

This single-blind, crossover study aimed to measure and evaluate the short-term metabolic responses to continuous and intermittent hypoxic patterns in individuals with obesity. Indirect calorimetry was used to quantify changes in resting metabolic rate (RMR), carbohydrate (CHOox, %CHO), and fat oxidation (FATox, %FAT) in nine individuals with obesity pre and post: 1) breathing normoxic air [normoxic sham control (NS-control)], 2) breathing continuous hypoxia (CH), or 3) breathing intermittent hypoxia (IH). A mean peripheral oxygen saturation ([Formula: see text]) of 80-85% was achieved over a total of 45 min of hypoxia. Throughout each intervention, pulmonary gas exchanges, oxygen consumption (V̇o2) carbon dioxide production (V̇co2), and deoxyhemoglobin concentration (Δ[HHb]) in the vastus lateralis were measured. Both RMR and CHOox measured pre- and postinterventions were unchanged following each treatment: NS-control, CH, or IH (all P > 0.05). Conversely, a significant increase in FATox was evident between pre- and post-IH (+44%, P = 0.048). Although the mean Δ[HHb] values significantly increased during both IH and CH (P < 0.05), the greatest zenith of Δ[HHb] was achieved in IH compared with CH (P = 0.002). Furthermore, there was a positive correlation between Δ[HHb] and the shift in FATox measured pre- and postintervention. It is suggested that during IH, the increased bouts of muscle hypoxia, revealed by elevated Δ[HHb], coupled with cyclic periods of excess posthypoxia oxygen consumption (EPHOC, inherent to the intermittent pattern) played a significant role in driving the increase in FATox post-IH.

Continuous Hypobaric Hypoxia may Promote Atherosclerosis Progression in Apolipoprotein E-deficient Mice.

Background: Intermittent normobaric hypoxia can promote the progression of atherosclerotic plaques. However, the effect of continuous hypobaric hypoxia (CHH), which is a major feature of high-altitude environment, on atherosclerosis has not been investigated thoroughly. Materials and Methods: After eight weeks of high-cholesterol diet, 30 male ApoE-/- mice were randomly divided into control and CHH groups. Mice in the CHH group lived in a hypobaric chamber with an oxygen content of 10% and air pressure of 364 mmhg (equal to 5,800 m altitude above sea level) for 4 weeks, while mice in the control group lived in normoxia condition. Then all mice were euthanized and the atherosclerotic lesion size and plaque stability in the aortic root were assessed. Intraplaque angiogenesis was characterized by immunostaining of CD31 and endomucin, which are identified as specific markers of vascular endothelial cells. Immunohistochemistry and qRT-PCR were performed to measure inflammatory cytokines. Results: Four weeks of CHH exposure promoted the growth of atherosclerotic lesions (p=0.0017) and decreased the stability of atherosclerotic plaques. In CHH group, plaque smooth muscle cells and collagen contents decreased, while plaque macrophages and lipids contents increased significantly (p<0.001). The contents of CD31 (p=0.0379) and endomucin (p=0.0196) in the plaque was higher in the CHH group and correlated with angiogenesis progression. Further, the content of monocyte chemotactic protein-1 (p=0.0376) and matrix metalloproteinase-2 was significantly higher (p=0.0212) in the CHH group. Conclusions: CHH may accelerate atherosclerosis progression in ApoE-/- mice by promoting angiogenesis and inflammation.

English

Heart rate variability (HRV) is a tool capable of analysing and assessing the vegetative activity of the heart in various activities and situations. It consists of measuring the time that elapses between every two heartbeats over a period of time and expressing it in terms of mathematical and statistical equations. Other authors have analysed the influence of different stressors on HRV. In this work we are looking for the action of normobaric hypoxia (NH) on HRV. NH consists of breathing oxygen-depleted air simulating altitude training. The aim of the study is to determine the influence of HN on the time and frequency domains of HRV. We subjected 13 healthy subjects (recreational athletes) to two HN sessions. We used the iAltitude Trainer v2.7® simulator. The first was a hypoxia tolerance test (HTT) (10 minutes, 11% O2, equivalent to 5050m) and the second was an intermittent exposure (HNI) (14% O2, 3250m) in which periods of 4 minutes of hypoxia alternated with 4 minutes of normoxia for 64 minutes. For HRV analysis, a Polar H10® heart rate monitor, the HRV-elite® application and the Kubios-Standard® software were used. Data were taken 5 minutes before and after each session, and these values were compared using the Student´s t- test for paired data. None of the variables in the time (RRmean, SDNN, rMSSD, pNN50) or frequency (VLF, LF, HF, LF/HF) domains of HRV showed significant changes in either situation. HN did not cause changes in the stress levels of these subjects and was well tolerated, clinically and electrocardiographically. A tolerance test and a session of exposure to intermittent normobaric hypoxia are not sufficient stimuli to cause acute changes in HRV.

Effect of intermittent normobaric hypoxia exposure on acclimatization to high altitude by air induction

Background: In emergency like condition, defence personnel are deployed to high altitude without proper acclimatization. Maladaption at high altitude leads to high altitude illness like acute mountain sickness (AMS), high altitude pulmonary edema (HAPE) and high-altitude cerebral edema (HACE) which hampers the operational capabilities. Aims and Objectives: The aim of the present study was to assess the effect of intermittent normobaric hypoxia exposure (IHE) at sea level on different physiological responses during initial days of acclimatization at 3500m and 4000m altitudes in acute induction. Materials and Methods: The IHE subjects were exposed to 12% FIO2 (equivalent altitude 14500 ft) for 4 hrs/day for 4 consecutive days at sea level and 5th day they were inducted by air to 3500m altitude. Baseline recording of different physiological parameters like cardiovascular, respiratory, oxygen saturation and AMS score were measured at sea level as well as 3500m altitude on daily basis for 6 days to assess acclimatization status. To confirm acclimatization status at 3500m, on fifth day the IHE group subjects were transported by road to 4000m and again measured different basal physiological parameters (like cardiovascular, oxygen saturation and AMS score) for four consecutive days. Results: Different physiological parameters of IHE treated group were stabilized by day 4 of air induction at 3500m altitude. Whereas, at 4000m altitude, these parameters were stabilized by day 2 of induction. Conclusion: Acclimatization schedules of four days at 3500m and two days at 4000m are essential to avoid malacclimatization/or high-altitude illness.

Normobaric Hypoxia Exposure During Treadmill Aerobic Exercise After Stroke: A Safety and Feasibility Study.

ObjectiveTo evaluate the safety and feasibility of performing treadmill aerobic exercise in moderate normobaric hypoxia among chronic hemiparetic stroke survivors.DesignObservational study using convenience sampling.SettingResearch laboratory in a tertiary rehabilitation hospital.ParticipantsChronic hemiparetic stroke survivors who could walk at least 10-m with or without assistance and had no absolute contraindications to exercise testing.InterventionParticipants (three male and four female) were asked to complete three normobaric hypoxia exposure protocols within a single session. First, they were passively exposed to normobaric hypoxia through gradual reductions in the fraction of inspired oxygen (FIO2 = 20.9, 17.0, and 15.0%) while seated (5-min at each level of FIO2). Participants were then exposed to the same reductions in FIO2 during constant-load exercise performed on a treadmill at 40% of heart rate reserve. Finally, participants completed 20-min of exercise while intermittently exposed to moderate normobaric hypoxia (5 × 2-min at FIO2 = 15.0%) interspaced with 2-min normoxia intervals (FIO2 = 20.9%).Outcome MeasuresThe primary outcome was occurrence of adverse events, which included standardized criteria for terminating exercise testing, blood oxygen saturation (SpO2) <80%, or acute mountain sickness score >2. The increased cardiovascular strain imposed by normobaric hypoxia exposure at rest and during exercise was evaluated by changes in SpO2, heart rate (HR), blood pressure, and rating of perceived exertion (RPE).ResultsOne participant reported mild symptoms of nausea during exercise in normobaric hypoxia and discontinued participation. No other adverse events were recorded. Intermittent normobaric hypoxia exposure was associated with reduced SpO2 (MD = −7.4%, CI: −9.8 to −5.0) and increased HR (MD = 8.2, CI: 4.6 to 11.7) compared to intervals while breathing typical room air throughout the 20-min constant-load exercise period. The increase in HR was associated with a 10% increase in relative effort. However, reducing FIO2 had little effect on blood pressure and RPE measurements.ConclusionModerate normobaric hypoxia appeared to be a safe and feasible method to increase the cardiovascular strain of submaximal exercise in chronic hemiparetic stroke survivors. Future studies evaluating the effects of pairing normobaric hypoxia exposure with existing therapies on secondary prevention and functional recovery are warranted.

Morphological differences in the pancreas of normo- and hypertensive rats after joint exposure of intermittent hypoxia and melatonin

The morphological changes in the pancreas of normo- and hypertensive rats after combined exposure to intermittent normobaric hypoxia and melatonin were studied. The study was conducted in the autumn on 24 normotensive (Wistar line) and 24 spontaneously hypertensive (SHR line) male rats. Experimental rats were daily exposed to hypoxic gas mixture in special sealed chamber. Hypoxic gas mixture (12 % oxygen in nitrogen) was supplied into this chamber from the membrane gas separator element in the intermittent mode: 15 min deoxygenation/ 15 min reoxygenation for 2 h. Exogenous melatonin was orally administered to experimental animals at 10 h in the morning at a dose of 5 mg / kg once a day. The total duration of the experiment was 28 d. Histological preparations of pancreatic tissue were prepared according to the standard methods. The morphometry of the preparations digital images was performed using the computer program ImageJ. The nature and severity of morphological changes in the pancreas of the experimental spontaneously hypertensive rats (hyperplasia of the nucleolus in the nucleus of exocrinocytes, a decrease in the amount of connective tissue) suggests that the combined effect of intermittent normobaric hypoxia and melatonin increases the activity of the exocrine part of the pancreas. At the same time, the activity of the endocrine part of the pancreas decreases, as evidenced by a decrease in the linear dimensions and area of the Langerhans islets, as well as the number of endocrinocytes contained in them. In Wistar rats, the combined effect of intermittent hypoxia and melatonin leads to the appearance of morphological signs of increased activity of both exocrine and endocrine pancreas functions. Thus, after prolonged combined exposure to intermittent normobaric hypoxia and melatonin, morphological signs of increased exocrine pancreas activity appear in both normotensive and hypertensive rats. At the same time, the activity of the endocrine function of the pancreas in experimental Wistar rats increases, while in SHR rats, on the contrary, decreases.

Morphofunctional state of the lungs respiratory part in normotensive and hypertensive rats after combined exposure to intermittent hypoxia and melatonin

Aim. The purpose of this work was to study and compare the combined effect of intermittent normobaric hypoxia (INH) and melatonin on the morphological and biochemical indices of the lungs respiratory part in Wistar and spontaneous hypertensive rats (SHR). Material and methods. The studies were conducted on 48 young male rats Wistar and SHR lines. The experimental rats were daily exposed to hypoxic gas mixture (12 % oxygen in nitrogen) in intermittent mode: 15 min deoxygenation / 15 min reoxygenation for 2 hours. Animals also received oral melatonin at a dose of 5 mg /1 kg of body weight once daily.Results. The sizes of alveolus were reduced, but their number and placement density were increased in SHR rats after a combined effect of INH and melatonin. The results showed a significant decrease of the interalveolar septum thickness and a tendency to decrease of the hydroxyproline concentration in the lung tissue of the experimental rats, regardless of their line.Conclusions. The 28-day combined effect of INH and melatonin increase the total alveolar surface area and reduce the amount of connective tissue in the lungs of experimental rats. These changes can improve the efficiency of the intrapulmonary gas exchange processes.

Determining the time needed for workers to acclimatize to hypoxia

This study aimed to determine the influence of intermittent hypoxia and the days required for a worker to be acclimatized in high-altitude countries. We conducted an experimental study. Ten nonsmoking male students were randomly recruited from King Saud University. Fourteen days of exposure to intermittent normobaric hypoxia (15%) was the independent variable. Heart rate (HR), respiratory frequency (RF), minute ventilation (VE), respiratory exchange ratio (RER), tidal volume (VT), oxygen uptake (VO2),VO2/kg, VO2/HR, VE/VO2, and VE/VCO2 were the dependent variables. Our results showed that 12 days of exposure to intermittent hypoxia were sufficient for workers to acclimatize to hypoxia based on their respiratory responses (i.e., HR, RF, VE). This type of acclimatization session is very important for workers who are suddenly required to work in such an environment, because prolonged exposure to high altitude without acclimatization leads to cell death due to a lack of oxygen, and this, in turn, puts workers' lives at risk.

Carry-Over Quality of Pre-acclimatization to Altitude Elicited by Intermittent Hypoxia: A Participant-Blinded, Randomized Controlled Trial on Antedated Acclimatization to Altitude.

Intermittent normobaric hypoxia (IH) is increasingly used to pre-acclimatize for a sojourn to high altitude. There is a number of hypoxia – protocols observing the hypoxic ventilatory response (HVR), but little is known about the carry – over quality of the Lake Louise Score (LLS). We thus studied a week – long, 1 h per day poikilocapnic hypoxia protocol on whether acclimatization could be carried over for one week. Rationale for this was that it usually takes one week to get from Europe, Britain or the United States to the base camp of a major mountain. Forty-nine healthy volunteers of both sexes were exposed to daily bouts of 1 h at an inspiratory fraction of oxygen (FiO2) of 0.11 or 0.21 (control) for 7 consecutive days. Seven days after cessation of IH or sham exposures participants were again subjected to hypoxia (FiO2 = 0.11) for 6 h and measurements of isocapnic HVR and blood gases out of the arterialized earlobe were taken and LLS was assessed. In those with IH exposures LLS was reduced which was not the case in those with sham exposure (87 vs. 50%). Changes in HVR or the arterial hemoglobin saturation were not observed. Gender neither affected LLS nor HVR nor blood gases or carry -over quality. We found that our week – long, hypoxia protocol grants a reduction in LLS that can be carried over the time span of one week. In this way, antedated acclimatization may improve safety and comfort on the mountain.

Seasonal features of the combined effects of intermittent normobabic hypoxia and melatonin on the thyroid gland morphofunctional state

The aim of this work is to compare the effect of the combination influence of dosed intermittent normobaric hypoxia and melatonin in different seasons of the year on the morphofunctional state of the rats’ thyroid gland.Material and methods. The study was carried out on 48 male rats of the Wistar line. The hypoxic gas mixture (12% O2 and 88% N2) was daily given to experimental animals in intermittent mode: 15 minutes deoxygenation / 15 minutes reoxygenation for 2 hours. Melatonin was administered orally in a dose of 5 mg / kg at10.00 a.m. The total duration of the experiment was 28 days. Histological preparations were prepared according to a standard methodic. Histomorphometry of the digital images of preparations was carried out using the computer program «Image J».Results. It was shown that the thyroid gland of rats reacted differently to the combined effects of intermittent hypoxia and melatonin at different seasons. So the signs of the gland activity were increased after influence of hypoxia and melatonin in spring. It was evidenced by a smaller area of follicles and colloid, a smaller internal diameter of the follicles and colloid-accumulation index, a greater height of the thyrocytes and follicular-colloid index, a smaller width of the interlobar, interlobular and interfollicular connective tissue interlayers compared to the control. The prolonged exposure to intermittent hypoxia and melatonin in autumn decreased the area and height of the follicular epithelium, increased the internal diameter of the follicles, decreased the follicular-colloidal index and increased the colloid-accumulation index. This indicated a decrease in the activity of the thyroid gland.Conclusions. Thus, in the spring, the morphofunctional activity of the thyroid gland is moderately increased, and in the autumn period, on the contrary, decreases.

Effect of a Single Session of Intermittent Hypoxia on Erythropoietin and Oxygen‐Carrying Capacity

Intermittent hypoxia, defined as alternating bouts of breathing hypoxic and normoxic air, has the potential to improve oxygen‐carrying capacity through an erythropoietin‐mediated increase in hemoglobin mass. The purpose of this study was to determine the effect of a single exposure of intermittent normobaric hypoxia on erythropoietin levels and hemoglobin mass in young healthy individuals. Nineteen healthy individuals (10 women and 9 men, age: 24 ± 4 years, height: 174 ± 11 cm, weight: 72.2 ± 12.2 kg) participated in the study. Participants were randomly assigned to an intermittent hypoxia group (Hyp, n = 10) or a placebo intermittent normoxia group (Norm, n = 9). Intermittent hypoxia consisted of five 4‐min hypoxic cycles at a targeted arterial oxygen saturation of 90% interspersed with 4‐min normoxic cycles. Air was made hypoxic by titrating nitrogen to a breathing circuit connected to a tank of compressed air. Nitrogen was not added to the breathing circuit in the intermittent normoxia condition. Pulmonary gas exchange, arterial oxygen saturation, and hemodynamics, using finger plethysmography, were continuously assessed during the intervention. Erythropoietin levels were measured before and two hours following the completion of the protocol. Hemoglobin mass was assessed using the carbon monoxide rebreathing technique the day before and seven days after exposure to intermittent hypoxia or normoxia. As anticipated, the intermittent hypoxia group had a lower arterial oxygen saturation than the intermittent normoxia group during the intervention (Hyp: 89 ± 1 vs. Norm: 98 ± 1%, p &lt; 0.01), which was equivalent to a lower fraction of inspired oxygen (Hyp: 0.119 ± 0.008, Norm: 0.209 ± 0.001, p &lt; 0.01). Erythropoietin levels did not significantly increase following exposure to intermittent hypoxia (Hyp: 8.2 ± 4.5 to 9.0 ± 4.8, Norm: 8.9 ± 1.7 to 11.1 ± 2.1 mU/ml, p = 0.56). Hemoglobin mass did not change following exposure to intermittent hypoxia (Hyp: 10.6 ± 1.4 to 10.2 ± 1.4, Norm: 9.7 ± 1.6 to 9.4 ± 1.5 g/kg, p = 0.48). Exposure to intermittent hypoxia did not affect mean arterial pressure (Hyp: 91 ± 6 to 90 ± 6, Norm: 93 ± 12 to 93 ± 12 mmHg, p = 0.84) or heart rate (Hyp: 68 ± 8 to 74 ± 9, Norm: 68 ± 8 to 68 ± 8 mmHg, p = 0.27). Respiratory rate, tidal volume, end‐tidal CO2 and total minute ventilation were not affected by intermittent hypoxia. Thus, a 40‐min session of intermittent hypoxia was not sufficient to elicit a rise in erythropoietin levels or oxygen‐carrying capacity in young healthy individuals. A longer exposure to intermittent hypoxia at a lower arterial oxygen saturation may be necessary to trigger an erythropoietin‐mediated increase in hemoglobin mass in young healthy individuals.

High-Altitude Hypoxia Decreases Plasma Erythropoietin Soluble Receptor Concentration in Lowlanders.

Background: The soluble form of the erythropoietin (Epo) receptor (sEpoR) is an endogenous antagonist of Epo. Decreasing plasma sEpoR increases free Epo, thereby increasing the availability of the hormone. In humans, short-term intermittent normobaric hypoxia exposure reduces sEpoR concentration in plasma. However, whether similar changes occur during continuous hypoxia, such as during high-altitude exposure with ongoing acclimatization, is yet unknown. Therefore, this study aimed to characterize the time-course concentration profile of sEpoR, and also of Epo, reticulocyte count (RC), and hematocrit in healthy lowlanders during 4 days at high altitude.Methods: Twenty-two men residents at sea level traveled by road (∼7 hours) from Lima to Cerro de Pasco (4340 m) for 72 hours. Oxygen saturation as measured by pulse oximetry (SpO2), heart rate, systolic and diastolic blood pressure, Lake Louise Score, sEpoR, Epo, RC, and hematocrit were evaluated every 12 hours, starting 12 hours before the ascent.Results: Plasma sEpoR decreased by 19% and remained below baseline values throughout high-altitude exposure. In parallel, Epo levels increased during the first hours, reaching a peak at 48 hours, and then progressively decreased until 72 hours. As a result, the Epo-to-sEpoR ratio (Epo/sEpoR) remained significantly elevated compared with baseline values. RC increased linearly until the end of the protocol, and hematocrit only showed a marginal increase.Conclusion: Our results show that high-altitude hypoxia causes a significant and stable reduction of plasma sEpoR concentration within the first 24 hours, whereas plasma Epo constantly decreases after having reached a maximum by 48 hours. This simultaneous change leads to a relatively high Epo/sEpoR after 72 hours at high altitude. The early increase in hematocrit likely relates to hemoconcentration, but the steady increase in RC reflects a sustained erythropoietic drive that will lead to elevate hematocrit to a new steady state after acclimatization.

The combined effect of intermittent normobaric hypoxia and melatonin on the morphological changes of the spontaneously hypertensive rats pancreas

The aim of the study was to investigate the morphological changes in the pancreas of spontaneously hypertensive animals after the combined effect of intermittent normobaric hypoxia (INH) and melatonin.Materials and methods. The study was carried out in spring on 24 spontaneously hypertensive male rats (SHR line). The experimental animals were daily given a hypoxic gas mixture (12 % oxygen in nitrogen) in an intermittent mode: 15 min deoxygenation/15 min reoxygenation for 2 hours. The same rats were daily administered orally with exogenous melatonin at 10.00 at a dose of 5 mg/kg. The duration of the experiment was 28 days. Histological preparations were prepared according to a standard procedure. Morphometry of the digital images of preparations was performed using the computer program ImageJ.Results. Based on changes in morphometric parameters (reduction in the size of acini, exocrinocytes, height of the epithelium), it can be assumed that the combined effect of INH and melatonin reduces the activity of the exocrine function of the pancreas. In the endocrine part of the pancreas of experimental animals morphological signs of its activation were noted: the linear dimensions of the Langerhans islets, the number and the density of their endocrine cells increased. Experimental animals also showed a decrease in the width of interlobular and interacinar interlayers of connective tissue, which can be considered as a manifestation of the mechanism of structural adaptation that facilitates the transport of oxygen and nutrients to the parenchymal elements of the pancreas.Conclusions. The combined effect of intermittent normobaric hypoxia and melatonin leads to the appearance of morphological signs of a decrease in the activity of the exocrine part of the pancreas in hypertensive rats. At the same time, the activity of the endocrine gland function in these animals increased.

HEPATOPROTECTIVE EFFECT OF INTERMITTENT NORMOBARIC HYPOXIA UNDER THE RADIATION THERAPY OF THE RAT LIVER

Aim. To study the effect of intermittent normobaric hypoxia (INH) during local irradiation of the rat liver in therapeutic doses (total focal dose 30 Gy for 10 fractions) on the biochemical parameters of blood serum characterizing liver function. Materials and methods. Blood sampling in the animals of the control group and in three tested groups was performed prior to the experiment and following the experiment (after 20 days), respectively. The following criteria of hepatocyte toxicity were investigated: the level of the general and direct bilirubin, general cholesterol and triglycerides, high- and low-density lipoproteins, alanine aminotransferase and aspartate aminotransferase activity. Blood tests were performed using a Sapphire-400 (Tokyo Boeki ltd, Japan) automatic clinical analyzer with the standard Cormay (Poland) sets of reactants. Results. The experiment showed that the local radiation therapy on the liver region led to a growth in the indicators of pigment exchange, total cholesterol, low-density lipoproteins, triglycerides zdfl and transaminase activity. At the same time, the high-density lipoprotein level decreased. In the tested animals, INH application caused an increase in the bilirubin level and a change in lipid exchange indicators of the opposite direction in comparison with the animals receiving radiation therapy. INH did not change the transaminase activity. Liver radiation against the INH background led to less pronounced changes in blood biochemical indicators than in the group of animals having received exclusively radiation therapy. Such changes in blood indicators can be explained by a radioprotective effect of intermittent normobaric hypoxia. Conclusion. Intermittent normobaric hypoxia has a normalizing effect on the blood biochemical indices when performing local radiation therapy on the liver region.

Морфологічні зміни щитоподібної залози спонтанно-гіпертензивних щурів після поєднаного впливу переривчастої нормобаричної гіпоксії та мелатоніну

The purpose of our work was to study the combined effects of intermittent normobaric hypoxia (INH) and melatonin on morphological changes of the thyroid gland of spontaneously hypertensive rats. The study was conducted on 24 spontaneously hypertensive (SHR lines) male rats in the spring period of the year. At the end of the experiment, the age of the animals was 4 months. Blood pressure in rats was determined at the caudal artery using a sphygmomanometer (S-2 “SHE” Germany). The rats were divided into 2 groups: I – control animals, and II – rats exposed to combined INH and melatonin. The experimental animals were daily given a hypoxic gas mixture (12 % O 2 ) in intermittent mode: 15 min deoxygenation/15 min reoxygenation during 2 hours. Another time of day (22 hours) the rats breathed air. Melatonin (“Unipharm Inc., USA”) was daily administered orally in a dose of 5 mg/kg at 10.00 a.m. The total duration of the experiment was 28 days. Histological preparations were prepared according to a standard methodic. Histomorphometry of the digital images of preparations was carried out using the computer program «Image J». It was found that 28-day combined effect of INH and melatonin has morphological signs of increasing the functional activity of the thyroid of spontaneously hypertensive rats. This is indicated by a decrease in the size of the follicles and colloid, an increase in the number of thyroid cells in the follicle, an increase in the follicular-colloidal index and a decrease in the colloid accumulation index, and a decrease in the width of the interfollicular connective tissue layers. These data may have not only a theoretical value, but also some practical interest in the use of hypoxic gas mixtures and melatonin to enhance the function of the thyroid gland in people suffering from arterial hypertension.

Intermittent normobaric hypoxia facilitates high altitude acclimatization by curtailing hypoxia-induced inflammation and dyslipidemia.

Intermittent hypoxic training (IHT) is a discrete cost-effective method for improving athletic performance and high altitude acclimatization. Unfortunately, IHT protocols widely vary in terms of hypoxia severity, duration, and number of cycles affecting physiological outcomes. In the present study, we evaluated the efficacy of a moderate normobaric IHT protocol (12% FiO2 for 4h, 4days) on acclimatization to high altitude (3250m). Global plasma proteomics studies revealed that IHT elicited acute-phase response proteins like C-reactive protein (CRP), serum amyloid A-1 protein (SAA), and alpha-1-acid glycoprotein 2 (AGP 2) as well as altered levels of several apolipoproteins. On subsequent exposure to high altitude, the IH trained volunteers exhibited significant higher arterial oxygen saturation with concomitant lower incidences of acute mountain sickness (AMS) as compared to controls. Interestingly, IH trained subjects exhibited lower levels of positive acute-phase proteins like C-reactive protein (CRP), serum amyloid A-1 protein (SAA), and fibrinogen (FGA, FGB, and FGG) both after days 4 and 7 of high altitude ascent. High altitude exposure also decreased the levels of HDL, LDL, and associated proteins as well as key enzymes for assembly and maturation of lipoprotein particles like lecithin-cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), and phospholipid transfer protein (PLTP). In contrast, IHT curtailed hypoxia-induced alterations of HDL, LDL, Apo-AI, Apo-B, LCAT, CETP, and PLTP. Further validation of results also corroborated attenuation of hypoxia-induced inflammation and dyslipidemia by IHT. These results provide molecular evidences supporting the use of moderate IHT as a potential non-pharmacological strategy for high altitude acclimatization.

Peculiarities of psychophysiological adaptation of marine cadets during professional training in marine specialities

Introduction.Occupational environment and occupational factors determine peculiarities in mastering marine occupations. Some unfavorable occupational educational and ecologic factors appear to cause high level of physical and psychoemotional stress.Objectiveis to study features of adaptation to study during occupational training in marine specialties in cadets of a higher marine educational institution, and to conduct medical and psychological rehabilitation.Material and methods.Examination covered 120 male cadets of 3rd and 4thyears of study: 70 (main group) and 50 (reference group). The age of the cadets was 21±0.4 years. To study characteristics of the cadets’ adaptation, the authors used psychological methods — Spielberger’s State Trait Anxiety Scale and Nemchin’s «Method measuring severity of neuropsychic stress». Statistical analysis was performed with software «Statistica for Windows 10.0».Study results and discussion.After 3 months of sailing, majority of the cadets appeared to be dysadapted. Deep clinical and laboratory studies proved that 39.4% of the examinees were apparently healthy and 60.6% of those had chronic diseases. Thus, a system of medical psychologic rehabilitation was designed, comprising primary and secondary prophylaxis methods. One of these prevention methods is a recovery complex of measures with intermittent normobaric hypoxia modified by us. The authors determined optimal regime of using intermittent normobaric hypoxia combined with medical rehabilitation.Conclusions.Adaptational state in cadets of high marine educational institution during professional training in marine occupations is characterized by increased psycho-emotional strain, anxiety and observed in 57.3% of the examinees. Findings are that after 3 months of sailing, majority of the cadets are dysadapted. To prevent morbidity and preserve health, the authors suggested a system of medical and psychologic rehabilitation including intermittent normobaric hypoxia with rehabilitation medical complex. The medical and prophylactic measures help to solve problems of psycho-emotional stress, lower morbidity parameters, prevent dysadaptation disorders, relieve functional overstrain. That preserves and improves the cadets’ health and forms an important stage in prevention of mental and behavioral disorders related to work.