Effect Of Intermittent Hypobaric Hypoxia Research Articles

Protective effect of intermittent hypobaric hypoxia against radiation-induced liver damage in Sprague-Dawley rats.

Without timely and effective interventions or treatments, radiation-induced liver damage (RILD) can lead to serious consequences for the patients and their families. To investigate the protective effect of intermittent hypobaric hypoxia preconditioning (IHHP) in RILD. Male adult SD rats were randomly divided into 8 groups including one control group, one only irradiation group and other experimental groups. Blood routine tests and liver function tests were all assessed with abdominal venous blood. Moreover, hematoxylin eosin (HE) staining and immunohistochemistry assay were used to detect the histopathological changes and expressions of transforming growth factor-β1 (TGF-β1), tumor necrosis factor α (TNF-α) and hypoxia-inducible factor 1α (HIF-1α) in radiated liver sections. Blood routing tests showed that RBC, WBC and Hb were all significantly increased while the differences of these results between different groups with same simulated altitude were approximate. However, liver function in the IHHP plus irradiation at 4000 m group was significantly decreased (P< 0.05) compared to only irradiation groups, and the manifestation of HE and lower positive expression of TNF-α showed improved histopathological changes in the liver section. Furthermore, no significant difference of HIF-1α expression between any two groups treated with IHHP was observed. IHHP at the altitude of 4000 m group could alleviate the radioactive liver damage by downregulating TNF-α and less strong positive expression of TGF-β1. Furthermore, patients exposed to radiation might benefit from this treatment to prevent or reduce the RILD.

Intermittent Hypobaric Hypoxia Ameliorates Autistic-Like Phenotypes in Mice.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by persistent deficits in social communication and stereotyped behaviors. Although major advances in basic research on autism have been achieved in the past decade, and behavioral interventions can mitigate the difficulties that individuals with autism experience, little is known about the many fundamental issues of the interventions, and no specific medication has demonstrated efficiency for the core symptoms of ASD. Intermittent hypobaric hypoxia (IHH) is characterized by repeated exposure to lowered atmospheric pressure and oxygen levels, which triggers multiple physiological adaptations in the body. Here, using two mouse models of ASD, male Shank3B -/- and Fmr1 -/y mice, we found that IHH training at an altitude of 5,000 m for 4 h per day, for 14 consecutive days, ameliorated autistic-like behaviors. Moreover, IHH training enhanced hypoxia inducible factor (HIF) 1α in the dorsal raphe nucleus (DRN) and activated the DRN serotonergic neurons. Infusion of cobalt chloride into the DRN, to mimic IHH in increasing HIF1α expression or genetically knockdown PHD2 to upregulate HIF1α expression in the DRN serotonergic neurons, alleviated autistic-like behaviors in Shank3B -/- mice. In contrast, downregulation of HIF1α in DRN serotonergic neurons induced compulsive behaviors. Furthermore, upregulating HIF1α in DRN serotonergic neurons increased the firing rates of these neurons, whereas downregulation of HIF1α in DRN serotonergic neurons decreased their firing rates. These findings suggest that IHH activated DRN serotonergic neurons via upregulation of HIF1α, and thus ameliorated autistic-like phenotypes, providing a novel therapeutic option for ASD.

Effect of Intermittent Hypobaric Hypoxia Exposure on HIF-1α, VEGF, and Angiogenesis in the Healing Process of Post-Tooth Extraction Sockets in Rats.

The aim of this study was to investigate the effect of intermittent hypobaric hypoxia (IHH) exposure on the expression of hypoxia-induced factor-1α (HIF-1α) messenger RNA (mRNA), vascular endothelial growth factor-a (VEGF-a) mRNA, and angiogenesis after tooth extraction in rats. On 45 male Sprague-Dawley rats were performed the removal of the maxillary left first molar, and then they were randomly divided into 9 groups, namely: 4 groups that were exposed to IHH for 30 minutes every day in the Hypobaric Chamber at an altitude of 18,000 feet, with 1 time hypobaric hypoxia (HH), 3 times HH, 5 times HH, and 7 times HH; 4 normoxia groups that were terminated on days 1, 3, 5, and 7 after tooth extraction; and the 1 control group. Real-time polymerase chain reaction measured the molecular changes in the socket tissue after tooth extraction in rats to evaluate the expression of HIF-1α mRNA and VEGF mRNA. Histological changes with hematoxylin and eosin staining were noted to evaluate the amount of angiogenesis in the socket after tooth extraction. Molecular and histological parameters were calculated at the end of each experiment on days 0, 1, 3, 5, and 7 after tooth extraction, which exhibited the improvement phase of the wound-healing process. Increases in the expression of HIF-1α mRNA, VEGF mRNA, and angiogenesis were found in the IHH group compared with the normoxia group and the control group. The expression of HIF-1α mRNA increased significantly (p < 0.05) in the group after one time HH exposure on day 1, then decreased in the IHH group (three times HH exposure, five times HH exposure, and seven times HH exposure) approaching the control group. The expression of VEGF mRNA and angiogenesis began to increase after one time HH exposure on day 1, and increased again after three times HH exposure on day 3, then increased even more after five times HH exposure on day 5, and increased very significantly (**p < 0.05) after seven times HH exposure on day 7. It showed that repeated or intermittent exposure to HH conditions induced a protective response that made cells adapt under hypoxia conditions. IHH exposure accelerates the socket healing of post-tooth extraction, which is proven by changes in HIF-1α mRNA expression and increase in VEGF mRNA expression as stimuli for angiogenesis in post-tooth extraction sockets under hypobaric hypoxic condition, which also stimulates the formation of new blood vessels, thereby increasing blood supply and accelerating wound healing.

Biomechanical and structural responses of the aorta to intermittent hypobaric hypoxia in a rat model

High altitude hypoxia is a condition experienced by diverse populations worldwide. In addition, several jobs require working shifts where workers are exposed to repetitive cycles of hypobaric hypoxia and normobaric normoxia. Currently, few is known about the biomechanical cardiovascular responses of this condition. In the present study, we investigate the cycle-dependent biomechanical effects of intermittent hypobaric hypoxia (IHH) on the thoracic aorta artery, in terms of both structure and function. To determine the vascular effects of IHH, functional, mechanical and histological approaches were carried out in the thoracic aorta artery, using uniaxial, pre-stretch, ring opening, myography, and histological tests. Three groups of rats were established: control (normobaric normoxia, NN), 4-cycles of intermittent hypoxia (short-term intermittent hypobaric hypoxia, STH), and 10-cycles of intermittent hypoxia (long-term intermittent hypobaric hypoxia, LTH). The pre-stretch and ring opening tests, aimed at quantifying residual strains of the tissues in longitudinal and circumferential directions, showed that the hypoxia condition leads to an increase in the longitudinal stretch and a marked decrease of the circumferential residual strain. The uniaxial mechanical tests were used to determine the elastic properties of the tissues, showing that a general stiffening process occurs during the early stages of the IH (STH group), specially leading to a significative increase in the high strain elastic modulus (E_{2}) and an increasing trend of low strain elastic modulus (E_{1}). In contrast, the LTH group showed a more control-like mechanical behavior. Myography test, used to assess the vasoactive function, revealed that IH induces a high sensitivity to vasoconstrictor agents as a function of hypoxic cycles. In addition, the aorta showed an increased muscle-dependent vasorelaxation on the LTH group. Histological tests, used to quantify the elastic fiber, nuclei, and geometrical properties, showed that the STH group presents a state of vascular fibrosis, with a significant increase in elastin content, and a tendency towards an increase in collagen fibers. In addition, advanced stages of IH (LTH), showed a vascular remodeling effect with a significant increase of internal and external diameters. Considering all the multidimensional vascular effects, we propose the existence of a long-term passive adaptation mechanism and vascular dysfunction as cycle-dependent effects of intermittent exposures to hypobaric hypoxia.

Intermittent hypobaric hypoxia causes deleterious effects on the reproductive system in female rats

BackgroundsNumerous studies have revealed that hypobaric hypoxia exposure elicited imbalance of homeostasis. However, the effects of intermittent hypobaric hypoxia (IHH) exposure on the female reproductive system have been rarely reported. This study aims to assess the effects of IHH on rat female reproductive system and explore the corresponding mechanism at the histological, endocrine and molecular levels. MethodsThe female rats were randomly divided into control and IHH groups. Multiple pathophysiological parameters, including body weight gain, organ coefficients, estrus cycle, and health signs were measured. Also, the reproductive hormones, hormone receptor mRNA expression and oxidant/antioxidant level were evaluated. ResultsSignificant increases of the heart, liver and lung coefficients were observed after IHH exposure. There were no statistically significant differences in ovarian and uterine coefficients, but changes were found in the morphology of the ovary and uterus. Additionally, the diestrus phase duration was significantly increased during IHH exposure. Furthermore, estrogen increased and the Luteinizing hormone and progesterone decreased after IHH exposure. Altered expression of ER, PR and LHR were also found in the IHH exposed rats. Importantly, IHH exposure significantly repressed the activities of GSH-Px and T-SOD and improved the contents of MDA. ConclusionsOur results evince that IHH exposure caused estrus cycle irregularity. IHH induced oxidative stress along with ovarian and uterine structure damages, reproductive hormone disturbances and unusual expression of hormone receptors, thus suggesting a potential mechanism underlying IHH-induced reproductive system dysfunction.

The effect of intermittent hypobaric hypoxia on oxidative stress status and antioxidant enzymes activity in rat brain

Background: High altitude can cause hypobaric hypoxia (HH), resulted from the lower barometric pressure and hence partial pressure of oxygen. Hypoxia can lead to a lot of deleterious molecular and cellular changes, such as generation of free radicals or reactive oxygen species (ROS). Increasing of ROS can cause oxidative stress if the antioxidant enzyme does not increase simultaneously. Oxidative damage in brain has toxic effect on cognitive functions.&#x0D; Objective: In this study, we investigate effect of acute intermittent HH on oxidative stress and antioxidant enzyme activity in rat brain.&#x0D; Method: Wistar rats divided into 5 groups, consisting control group and four experimental groups which treated to HH. Rats were exposed to simulated HH equivalent to 35.000 feet in hypobaric chamber for 1 minute, repeated once a week.&#x0D; Results: Level of malondialdehyde and carbonyl in rat brain under acute HH increased at HH exposure (group I) compare to control group. These levels decreased afterward at intermittent HH exposure (group II-IV). Specific activity of superoxide dismutase (SOD) shows increasing level at intermittent HH exposure, especially group IV was increasing of SOD level significantly. The increasing pattern of specific activity of catalase was inversely from SOD pattern, but it still has higher activity in intermittent HH compare to control group.&#x0D; Conclusion: Brain tissue seems to be able to perform an adequate adaptive response to hypobaric hypoxia after the training, shown by its significantly decreased MDA and carbonyl level and also increased specific activity of SOD and catalase.

Additive Effects of Intermittent Hypobaric Hypoxia and Endurance Training on Bodyweight, Food Intake, and Oxygen Consumption in Rats.

Cabrera-Aguilera, Ignacio, David Rizo-Roca, Elisa A. Marques, Garoa Santocildes, Teresa Pagès, Gines Viscor, António A. Ascensão, José Magalhães, and Joan Ramon Torrella. Additive effects of intermittent hypobaric hypoxia and endurance training on bodyweight, food intake, and oxygen consumption in rats. High Alt Med Biol. 19:278-285, 2018.-We used an animal model to elucidate the effects of an intermittent hypobaric hypoxia (IHH) and endurance exercise training (EET) protocol on bodyweight (BW), food and water intake, and oxygen consumption. Twenty-eight young adult male rats were divided into four groups: normoxic sedentary (NS), normoxic exercised (NE), hypoxic sedentary (HS), and hypoxic exercised (HE). Normoxic groups were maintained at an atmospheric pressure equivalent to sea level, whereas the IHH protocol consisted of 5 hours per day for 33 days at a simulated altitude of 6000 m. Exercised groups ran in normobaric conditions on a treadmill for 1 hour/day for 5 weeks at a speed of 25 m/min. At the end of the protocol, both hypoxic groups showed significant decreases in BW from the ninth day of exposure, reaching final 10% (HS) to 14.5% (HE) differences when compared with NS. NE rats also showed a significant weight reduction after the 19th day, with a decrease of 7.4%. The BW of hypoxic animals was related to significant hypophagia elicited by IHH exposure (from 8% to 12%). In contrast, EET had no effect on food ingestion. Total water intake was not affected by hypoxia but was significantly increased by exercise. An analysis of oxygen consumption at rest (mL O2/[kg·min]) revealed two findings: a significant decrease in both hypoxic groups after the protocol (HS, 21.7 ± 0.70 vs. 19.1 ± 0.78 and HE, 22.8 ± 0.80 vs. 17.1 ± 0.90) and a significant difference at the end of the protocol between NE (21.3 ± 0.77) and HE (17.1 ± 0.90). These results demonstrate that IHH and EET had an additive effect on BW loss, providing evidence that rats underwent a metabolic adaptation through a reduction in oxygen consumption measured under normoxic conditions. These data suggest that the combination of IHH and EET could serve as an alternative treatment for the management of overweight and obesity.

Contractile Activity Is Necessary to Trigger Intermittent Hypobaric Hypoxia-Induced Fiber Size and Vascular Adaptations in Skeletal Muscle.

Altitude training has become increasingly popular in recent decades. Its central and peripheral effects are well-described; however, few studies have analyzed the effects of intermittent hypobaric hypoxia (IHH) alone on skeletal muscle morphofunctionality. Here, we studied the effects of IHH on different myofiber morphofunctional parameters, investigating whether contractile activity is required to elicit hypoxia-induced adaptations in trained rats. Eighteen male Sprague-Dawley rats were trained 1 month and then divided into three groups: (1) rats in normobaria (trained normobaric inactive, TNI); (2) rats subjected daily to a 4-h exposure to hypobaric hypoxia equivalent to 4,000 m (trained hypobaric inactive, THI); and (3) rats subjected daily to a 4-h exposure to hypobaric hypoxia just before performing light exercise (trained hypobaric active, THA). After 2 weeks, the tibialis anterior muscle (TA) was excised. Muscle cross-sections were stained for: (1) succinate dehydrogenase to identify oxidative metabolism; (2) myosin-ATPase to identify slow- and fast-twitch fibers; and (3) endothelial-ATPase to stain capillaries. Fibers were classified as slow oxidative (SO), fast oxidative glycolytic (FOG), fast intermediate glycolytic (FIG) or fast glycolytic (FG) and the following parameters were measured: fiber cross-sectional area (FCSA), number of capillaries per fiber (NCF), NCF per 1,000 μm2 of FCSA (CCA), fiber and capillary density (FD and CD), and the ratio between CD and FD (C/F). THI rats did not exhibit significant changes in most of the parameters, while THA animals showed reduced fiber size. Compared to TNI rats, FOG fibers from the lateral/medial fields, as well as FIG and FG fibers from the lateral region, had smaller FCSA in THA rats. Moreover, THA rats had increased NCF in FG fibers from all fields, in medial and posterior FIG fibers and in posterior FOG fibers. All fiber types from the three analyzed regions (except the posterior FG fibers) displayed a significantly increased CCA ratio compared to TNI rats. Global capillarisation was also increased in lateral and medial fields. Our results show that IHH alone does not induce alterations in the TA muscle. The inclusion of exercise immediately after the tested hypoxic conditions is enough to trigger a morphofunctional response that improves muscle capillarisation.

Involvement of Autonomic Nervous System in Antiarrhythmic Effect of Intermittent Hypobaric Hypoxia.

We studied the involvement of the autonomic nervous system in the antiarrhythmic effect of intermittent hypobaric hypoxia modeled by daily placing the rats into an altitude chamber at 405 mm Hg (5000 m above sea level). The antiarrhythmic effect of hypoxia was observed on the model of acute coronary occlusion/reperfusion in vivo, but not during simulation of total ischemia/reperfusion of the isolated myocardium. Intravenous injection of ganglionic blocker hexamethonium (30 mg/kg) 15 min prior to in vivo coronary occlusion modeling abolished the antiarrhythmic effect of intermittent hypobaric hypoxia, which suggests that this effect is mediated via activation of the autonomic nervous system.

Intermittent hypobaric hypoxia combined with aerobic exercise improves muscle morphofunctional recovery after eccentric exercise to exhaustion in trained rats.

Unaccustomed eccentric exercise leads to muscle morphological and functional alterations, including microvasculature damage, the repair of which is modulated by hypoxia. We present the effects of intermittent hypobaric hypoxia and exercise on recovery from eccentric exercise-induced muscle damage (EEIMD). Soleus muscles from trained rats were excised before (CTRL) and 1, 3, 7, and 14 days after a double session of EEIMD protocol. A recovery treatment consisting of one of the following protocols was applied 1 day after the EEIMD: passive normobaric recovery (PNR), a 4-h daily exposure to passive hypobaric hypoxia at 4,000 m (PHR), or hypobaric hypoxia exposure followed by aerobic exercise (AHR). EEIMD produced an increase in the percentage of abnormal fibers compared with CTRL, and it affected the microvasculature by decreasing capillary density (CD, capillaries per mm2) and the capillary-to-fiber ratio (CF). After 14 days, AHR exhibited CD and CF values similar to those of CTRL animals (789 and 3.30 vs. 746 and 3.06) and significantly higher than PNR (575 and 2.62) and PHR (630 and 2.92). Furthermore, VEGF expression showed a significant 43% increase in AHR when compared with PNR. Moreover, after 14 days, the muscle fibers in AHR had a more oxidative phenotype than the other groups, with significantly smaller cross-sectional areas (AHR, 3,745; PNR, 4,502; and PHR, 4,790 µm2), higher citrate synthase activity (AHR, 14.8; PNR, 13.1; and PHR, 12 µmol·min-1·mg-1) and a significant 27% increment in PGC-1α levels compared with PNR. Our data show that hypoxia combined with exercise attenuates or reverses the morphofunctional alterations induced by EEIMD.NEW & NOTEWORTHY Our study provides new insights into the use of intermittent hypobaric hypoxia combined with exercise as a strategy to recover muscle damage induced by eccentric exercise. We analyzed the effects of hypobaric exposure combined with aerobic exercise on histopathological features of muscle damage, fiber morphofunctionality, capillarization, angiogenesis, and the oxidative capacity of damaged soleus muscle. Most of these parameters were improved after a 2-wk protocol of intermittent hypobaric hypoxia combined with aerobic exercise.

Effects of intermittent hypobaric hypoxia preconditioning on the expression of neuroglobin and Bcl-2 in the rat hippocampal CA1 area following ischemia-reperfusion.

This study was aimed at understanding the effect of intermittent hypobaric hypoxia preconditioning (IHHP) on neuroglobin (NGB) and Bcl-2 expression in the hippocampal CA1 region of rats following global cerebral ischemia-reperfusion. Wistar rats were randomly divided into sham, IHHP control, global cerebral ischemia-reperfusion (IR group), and IHHP+IR groups. The four-vessel occlusion rat model of Pulsinelli was used for the IR groups, in which the common carotid artery was occluded for 8 min before reperfusion. Thionin and immunohistochemical staining were used to observe NGB and Bcl-2 expression in the hippocampal CA1 region. Data was analyzed using the SPSS software. There was a significant increase in the number of surviving cells in the hippocampal CA1 region of the IHHP+IR group (119.5 ± 14) compared to the IR group (41.7 ± 3.8) (P < 0.05). There was a significant increase in the expression of NGB and Bcl-2 in the hippocampal CA1 region of the IHHP+IR group compared to the IR group. By upregulating hippocampal NGB and Bcl-2 expression, IHHP may play a role in neural protection by reducing hippocampal neuronal apoptosis following IR.

The sex related effects of intermittent hypobaric hypoxia on the oxidized modification of proteins in the gingival tissues in immature rats under conditions of changed photoperiod

It is shown in experiments that intermittent hypoxia (equivalent to the altitude 4000 meters, 2 hours per day for 14 days) changes the capacity of the oxidized modification of proteins (OMP) in the gingival tissues of immature albino rats. The result of hypoxic effects depends on the sex of animals: in males it causes a decrease of proteins peroxidation intensity both of basic and neutral nature; in females – only a tendency to decrease of the basic OMP.Functional state of the pineal gland changed by experimental conditions (14 days of illumination – “physiological pinealectomy”, or 14 days of darkness – stimulation of the pineal gland) influenced the effects of hypoxia on the OMP in the gingival tissues. The darkness heightens the decreasing effects of hypoxia on the capacity of OMP in the gingival, which is more pronounced in male rats.Our results suggest that by an application of combination of intermittent hypobaric hypoxia and the darkness it is possibleto prevent the process of accumulation of OMP in the gingival tissues.

Short-Term versus Long Term intermittent hypobaric hypoxia on cardiac fibrosis and cardioprotective effects of Natural antioxidants supplementation in rats hearts

Controversial effects of intermittent hypobaric hypoxia (IHH) such as cardiac damage or cardiac protection are still mysterious. It is unclear if short-term and long-term IHH challenges exert different changes of the pro-oxidant/antioxidant balance in the heart and throughout the body. It has been shown that natural antioxidants supplementation (Quercetin, Lycium barbarum and Chitosan) is effective in preventing the hypoxic stress. The aim of this study was to evaluate the protective effect of these natural antioxidants' administration in heart in animals exposed to IHH and therefore exposed to oxidative stress. One hundred male Wistar rats were randomized assigned into ten groups was exposed to short-term and long-term IHH (380 mmHg, 12% O2, 8h/day) for different periods of time (2 days or 4 weeks) or kept in normoxia for 4 weeks. Some of the rats were administered natural antioxidants cu 30 minute before each IHH exposure of IHH. After short-term IHH or long-term IHH challenge, myocardial morphology was determined by histological analysis. Myocardial sections were examined histopathologically to determine the cardiomyocyte viability and morphometry. The results show a negative effect of IHH on the cardiomyocyte viability and cardio-protective effects of natural antioxidants' administration. This study suggests that treatment with Quercetin, Lycium barbarum or Chitosan alone substantially restored the myocardial architecture and acted like cardioprotectants.

Blueberries prevent the effect of intermittent hypobaric hypoxia in rat epididymis

Intermittent hypobaric hypoxia (IHH) induced a decrease in sperm count and oxidative damage in epididymis. We have previously demonstrated that a blueberry-enriched polyphenol extract (BB-4) reduced the adverse effects of oxidative stress in rat testis under hypobaric hypoxia. The aim of this study was to evaluate whether BB-4 could reverse oxidative stress in epididymis. To evaluate the protective role of BB-4 in epididymis, male rats were exposed to IHH. Lipid peroxidation, (LPO) expression and activity of glutathione reductase (GR) were evaluated. Our results showed a reduction in LPO and a decrease in GR activity in rat epididymis exposed to IHH. These results suggest that BB-4 can prevent the effects of IHH in rat epididymis.

Mitochondrial energy metabolism plays a critical role in the cardioprotection afforded by intermittent hypobaric hypoxia

Intermittent hypobaric hypoxia (IHH) is an effective protective strategy against myocardial ischaemia-reperfusion (I/R) injury, but the precise mechanisms are far from clear. To understand the overall effects of IHH on the myocardial proteins during I/R, we analysed functional performance and the protein expression profile in isolated hearts from normoxic rats and from rats adapted to IHH (5000 m, 4 h day(-1), 4 weeks) following I/R injury (30 min/45 min). Intermittent hypobaric hypoxia significantly improved the postischaemic recovery of left ventricular function compared with the recovery in time-matched normoxic control hearts. Two-dimensional electrophoresis with matrix-assisted laser desorption/ionization and time-of-flight mass spectrometric analysis was then used to assess protein alterations in left ventricles from normoxic and IHH groups, with or without I/R. The expressions of 16 proteins changed by over fivefold; nine of these proteins are involved in energy metabolism. Immunoblot and real-time PCR analysis confirmed the IHH-increased expressions of the ATP synthase subunit β, mitochondrial aldehyde dehydrogenase and heat shock protein 27 in left ventricles. Furthermore, IHH significantly attenuated the reduction of myocardial ATP content, mitochondrial ATP synthase activity, membrane potential and respiratory control ratios due to I/R. In addition, inhibition of mitochondrial ATP synthase by oligomycin (1 μmol l(-1)) abolished the IHH-induced improvements in three parameters: postischaemic recovery of left ventricular function, mitochondrial membrane potential and respiratory control ratios. These results suggest that an improvement in mitochondrial energy metabolism makes an important contribution to the cardioprotection afforded by IHH against postischaemic myocardial dysfunction.

Therapeutic effect of intermittent hypobaric hypoxia on myocardial infarction in rats

Intermittent hypobaric hypoxia (IHH) preconditioning protects the heart against ischemic injuries. However, little is known about the therapeutic effect of IHH on myocardial infarction (MI). The aim of this study was to test whether IHH treatment influences infarct size and cardiac performance after MI. Seven days after sham operation or left anterior descending coronary artery ligation, male Sprague-Dawley rats were randomly exposed to normoxia or one 6-h period each day of IHH (5,000 m) for 14 and 28 days. Echocardiography analysis showed that IHH significantly reduced left ventricular (LV) dilation and improved cardiac performance after 14- or 28-day treatment compared with MI-normoxic groups. The improvement of LV function was further confirmed in isolated perfused MI-IHH hearts. Such protection was associated with attenuated infarct size, myocardial fibrosis, and apoptotic cardiomyocytes. IHH treatment also enhanced coronary flow and phosphorylation of heat shock protein 27 in both sham and MI groups compared with the control groups. In addition, IHH increased the capillary density and vascular endothelial growth factor expression in peri-infarcted zones compared with sham-IHH and MI-normoxic groups. Our data demonstrated for the first time that IHH treatment exerts a therapeutic effect on MI by attenuating progressive myocardial remodeling and improving myocardial contractility. IHH treatment might provide a unique and promising therapeutic approach for ischemic heart diseases.

Restructuring of the thyroid gland in primary hypothyroidism under the influence of intermittent hypobaric hypoxia

We studied the effect of intermittent hypobaric hypoxia on morphofunctional characteristics of the thyroid gland during experimental hypothyroidism. Functional activity of the thyroid gland increased in the early period of hypoxia. Morphofunctional parameters reached a constant level with increasing the duration of hypoxia to 7-15 days. A new functional level was characterized by increased activity and normal function of glandular cells.

The effect of intermittent hypobaric hypoxic exposure and sea level training on submaximal economy in well-trained swimmers and runners

To evaluate the effect of intermittent hypobaric hypoxia combined with sea level training on exercise economy, 23 well-trained athletes (13 swimmers, 10 runners) were assigned to either hypobaric hypoxia (simulated altitude of 4,000-5,500 m) or normobaric normoxia (0-500 m) in a randomized, double-blind design. Both groups rested in a hypobaric chamber 3 h/day, 5 days/wk for 4 wk. Submaximal economy was measured twice before (Pre) and after (Post) the treatment period using sport-specific protocols. Economy was estimated both from the relationship between oxygen uptake (V(.-)o2) and speed, and from the absolute V(.-)o2 at each speed using sport-specific protocols. V(.-)o2 was measured during the last 60 s of each (3-4 min) stage using Douglas bags. Ventilation (V(.-)E), heart rate (HR), and capillary lactate concentration ([La(-)]) were measured during each stage. Velocity at maximal V(.-)o2 (velocity at V(.-)o2max) was used as a functional indicator of changes in economy. The average V(.-)o2 for a given speed of the Pre values was used for Post test comparison using a two-way, repeated-measures ANOVA. Typical error of measurement of V(.-)o2 was 4.7% (95% confidence limits 3.6-7.1), 3.6% (2.8-5.4), and 4.2% (3.2-6.9) for speeds 1, 2, and 3, respectively. There was no change in economy within or between groups (ANOVA interaction P = 0.28, P = 0.23, and P = 0.93 for speeds 1, 2, and 3). No differences in submaximal HR, [La-], Ve, or velocity at V(.-)o2(max) were found between groups. It is concluded that 4 wk of intermittent hypobaric hypoxia did not improve submaximal economy in this group of well-trained athletes.

Improvement of myocardial perfusion in coronary patients after intermittent hypobaric hypoxia

Persons living at high altitude (exposed to hypoxia) have a greater number of coronary and peripheral branches in the heart than persons living at sea level. In this study we investigated the effect of intermittent hypobaric hypoxia on myocardial perfusion in patients with coronary heart disease. We studied 6 male patients (aged>or=53 years) with severe stable coronary heart disease. All patients were born at sea level and lived in that environment. They underwent 14 sessions of exposure to intermittent hypobaric hypoxia (equivalent to a simulated altitude of 4200 m). Myocardial perfusion was assessed at baseline and after treatment with hypoxia by use of exercise perfusion imaging with technetium 99m sestamibi. After the sessions of hypoxia, myocardial perfusion was significantly improved. The summed stress score for hypoperfusion, in arbitrary units, decreased from 9.5+ to 4.5+ after treatment (P=.036). There was no evidence of impairment of myocardial perfusion in any patient after treatment. Intermittent hypobaric hypoxia improved myocardial perfusion in patients with severe coronary heart disease. Though preliminary, our results suggest that exposure to intermittent hypobaric hypoxia could be an alternative for the management of patients with chronic coronary heart disease.

Effect of intermittent hypobaric hypoxia on the maximal hydraulic conductivity of the circulatory bed, capillarization, and size of muscle fibers in rats

Effect of intermittent hypobaric hypoxia on the maximal hydraulic conductivity of the circulatory bed, capillarization, and size of muscle fibers in rats