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Introduction: We assessed metabolic and hormonal responses to high-load resistance exercise under varying normobaric hypoxia conditions with a saturation clamp. Methods: Employing a counterbalanced, crossover test design, ten well-trained men participated in three exercise trials with normoxic or hypoxic gas mixtures to maintain arterial oxygen saturation at --90% and 80% [moderate (MH) and severe (SH) hypoxia, respectively]. The resistance exercise regimen comprised five sets of 10 repetitions of barbell back squats at 70% of one repetition maximum, with 1- min rest between sets. Metabolic and hormonal responses were measured before normoxia or hypoxia exposures (Pre 1), 15 min after the exposures (Pre 2), and at 0-, 15-, and 30-min post-exercises (T0, T15, and T30, respectively). Results: Compared to Pre 2, blood lactate concentrations and growth hormone values were elevated at T0, T15, and T30 (p ≤ 0.001), while testosterone values increased at T0 in all conditions (p ≤ 0.009). Epinephrine values increased significantly from Pre 2 to T0 in SH only (p < 0.001). SH had significantly higher blood lactate concentrations (p = 0.023), growth hormone (p = 0.050), and epinephrine (p = 0.020) values at T30 compared to NM. Cortisol values were elevated above Pre 2 at T15 in MH and SH, while lower testosterone values were noted at T0 and T15 for SH compared to NM and MH (all p ≤ 0.05). Discussion: Severe simulated hypoxia, achieved through a saturation clamp during barbell back squats, may enhance metabolic and hormonal responses, particularly 30 min post-session. Nevertheless, the acute effects of hypoxia exposure seem to be overridden by the impact of high-load resistance exercise. [ABSTRACT FROM AUTHOR]

Study purpose. This study investigated the effects of whole-body vibration (WBV) combined with blood flow restriction (BFR) and hypoxic exposure (HYP) on body composition and physical performance in overweight university students. Materials and methods. Twenty-nine male university students with overweight were divided into 3 groups: 1) whole-body vibration (WBV), 2) whole-body vibration plus blood flow restriction (WBV+BFR, 60% of occlusion pressure) and 3) whole-body vibration plus hypoxic exposure (WBV+HYP, FiO₂ = 15.8%). Training included 10 sets of intermittent WBV exercise (30-35 Hz in frequency and high amplitude) 20 min/day and 3 days/week. Body composition along with physical performance was measured before (2-3 days prior) and after (2-3 days post) an 8-week training period. Results. The results of this study were as followed, after training, the maximum strength (1RM) in the leg press and leg curl were significantly increased in the WBV+HYP group (28.31%, p = 0.016 and 13.56%, p = 0.017) compared with the WBV group (17.68% and 2.88) respectively. Similarly, the WBV+HYP group showed a substantial increase in muscle endurance in the leg extension and leg curl (28.57%, p = 0.013 and 34.38% p = 0.049) when compared to the WBV group (5.33% and 13.20%) respectively. Conclusions. Whole-body vibration combined with blood flow restriction and hypoxic exposure were effective in improving body composition and physical fitness. Performing the procedure can also be adjusted according to convenience and suitability for each individual. It is a guideline for preventing, treating, and promoting health among overweight adolescents.

Study purpose. This study investigated the effects of whole-body vibration (WBV) combined with blood flow restriction (BFR) and hypoxic exposure (HYP) on body composition and physical performance in overweight university students. Materials and methods. Twenty-nine male university students with overweight were divided into 3 groups: 1) whole-body vibration (WBV), 2) whole-body vibration plus blood flow restriction (WBV+BFR, 60% of occlusion pressure) and 3) whole-body vibration plus hypoxic exposure (WBV+HYP, FiO2 = 15.8%). Training included 10 sets of intermittent WBV exercise (30-35 Hz in frequency and high amplitude) 20 min/day and 3 days/week. Body composition along with physical performance was measured before (2-3 days prior) and after (2-3 days post) an 8-week training period. Results. The results of this study were as followed, after training, the maximum strength (1RM) in the leg press and leg curl were significantly increased in the WBV+HYP group (28.31%, p = 0.016 and 13.56%, p = 0.017) compared with the WBV group (17.68% and 2.88) respectively. Similarly, the WBV+HYP group showed a substantial increase in muscle endurance in the leg extension and leg curl (28.57%, p = 0.013 and 34.38% p = 0.049) when compared to the WBV group (5.33% and 13.20%) respectively. Conclusions. Whole-body vibration combined with blood flow restriction and hypoxic exposure were effective in improving body composition and physical fitness. Performing the procedure can also be adjusted according to convenience and suitability for each individual. It is a guideline for preventing, treating, and promoting health among overweight adolescents. [ABSTRACT FROM AUTHOR]

Abstract Repeated sprint exercise (RSE) is a popular training modality for a wide variety of athletic activities. The purpose of this study was to assess the combined effects of systemic hypoxia and blood flow restriction (BFR) on muscle deoxygenation and RSE performance. Twelve healthy young men performed a standard RSE training modality (five sets of 10 s maximal sprint with a 60 s rest) under four different conditions: (1) normoxic control (NC), normoxia (N, 20.9%) + control BFR (C, 0 mmHg); (2) normoxic BFR (NB), normoxia (N, 20.9%) + BFR (B, 140 mmHg); (3) hypoxic control (HC), hypoxia (H, 13.7%) + control BFR (C, 0 mmHg); and (4) hypoxic BFR (HB): hypoxia (H, 13.7%) + BFR (B, 140 mmHg). BFR was only administered during the rest period of the respective RSE trials. In the local exercising muscles, muscle oxygen saturation (SmO2) and neuromuscular activity were measured using near‐infrared spectroscopy and surface electromyography, respectively. SmO2 was lower in systemic hypoxia conditions relative to normoxia conditions (P 0.05). Interestingly, an elevated neuromuscular activity was seen in response to the BFR, particularly during conditions of systemic hypoxia (P

New Findings: What is the central question of this study?Does applying blood flow restriction during the rest periods of repeated sprint exercise in a hypoxic environment lead to greater local hypoxia within exercising muscles without compromising training workload?What is the main finding and its importance?Repeated sprint exercise with blood flow restriction administered during rest periods under systemic hypoxia led to severe local hypoxia within the exercised muscles without a reduction in power output. The maintained power output might be due to elevated neuromuscular activation. Accordingly, the proposed repeated sprint exercise in the current study may be an effective training modality. Repeated sprint exercise (RSE) is a popular training modality for a wide variety of athletic activities. The purpose of this study was to assess the combined effects of systemic hypoxia and blood flow restriction (BFR) on muscle deoxygenation and RSE performance. Twelve healthy young men performed a standard RSE training modality (five sets of 10 s maximal sprint with a 60 s rest) under four different conditions: (1) normoxic control (NC), normoxia (N, 20.9%) + control BFR (C, 0 mmHg); (2) normoxic BFR (NB), normoxia (N, 20.9%) + BFR (B, 140 mmHg); (3) hypoxic control (HC), hypoxia (H, 13.7%) + control BFR (C, 0 mmHg); and (4) hypoxic BFR (HB): hypoxia (H, 13.7%) + BFR (B, 140 mmHg). BFR was only administered during the rest period of the respective RSE trials. In the local exercising muscles, muscle oxygen saturation (SmO2$\textit{Sm}{O}_{2}$) and neuromuscular activity were measured using near‐infrared spectroscopy and surface electromyography, respectively. SmO2 was lower in systemic hypoxia conditions relative to normoxia conditions (P < 0.05). A rther decrease in SmO2 was observed in HB relative to HC (Set 1: HC 70.0 ± 17.5 vs. HB 57.4 ± 11.3%, P = 0.001; Set 4: HC 67.5 ± 14.6 vs. HB 57.0 ± 12.0%, P = 0.013; Set 5: HC 61.0 ± 15.3 vs. HB 47.7 ± 11.9%, P < 0.001). No differences in RSE performance were observed between any of the conditions (P > 0.05). Interestingly, an elevated neuromuscular activity was seen in response to the BFR, particularly during conditions of systemic hypoxia (P < 0.05). Thus, RSE with BFR administered during rest periods under systemic hypoxia led to severe local hypoxia without compromising training workload. [ABSTRACT FROM AUTHOR]

Purpose: Diabetic retinopathy (DR) is a hypoxic retinal disease, but so far, the association with systemic hypoxia is poorly understood. Hence, the aim of this study was to evaluate cross-sectional and longitudinal associations between DR and chronic respiratory failure (CRF) in a national cohort. Design: Cross-sectional and 5-year longitudinal register-based cohort study. Methods: Between 2013 and 2018, we included patients with diabetes from the Danish Registry of Diabetic Retinopathy, who were each age and sex matched with five controls without diabetes. At index date, the prevalence of CRF was compared between cases and controls, and the longitudinal relationship between DR and CRF was assessed in a five-year follow-up. Results: At baseline, we identified 1,980 and 9,990 patients with CRF among 205,970 cases and 1,003,170 controls. The prevalence of CRF was higher among cases than controls (OR 1.75, 95% CI 1.65–1.86), but no difference between cases with and without DR was found.During follow-up, we identified 1,726 and 5,177 events of CRF among cases and controls, respectively. The incidence of CRF was higher among both cases with and without DR compared to controls (DR level 0: HR 1.24, 95% CI 1.16–1.33, DR level 1–4: HR 1.86, 95% CI 1.63–2.12), and higher among cases with DR compared to cases without DR (HR 1.54, 95% CI 1.38–1.72). Conclusion: In this study based on nationwide data, we found an increased risk of present and incident CRF in patients with diabetes with or without DR, and we identified DR as a predictor of future CRF.

This study quantified performance and physiological responses during multi-set resistance exercise to failure at light versus moderate loads in normoxia and systemic hypoxia. On separate visits, fifteen resistance-trained adults performed barbell biceps curl exercise trials (6 sets to failure, 2 min rest between sets) in four separate randomised conditions; i.e. in normoxia at 380 m above sea level or systemic hypoxia at ∼3800 m simulated altitude (inspired oxygen fraction = 20.9% and 12.9%, respectively) combined with two different intensity levels (30% and 70% of 1 repetition maximal or 1RM). Muscle activation (root mean square value calculated from surface electromyography) and oxygenation (integrated-tissue saturation index derived from near-infrared spectroscopy) were monitored for the biceps brachii muscle. The total number of repetitions before failure at 30% 1RM (122 ± 5 vs. 131 ± 5; P = 0.021), but not 70% 1RM (39 ± 1 vs. 41 ± 2; P = 0.313), was lower in hypoxia compared to normoxia. Root mean square activity of the biceps brachii muscle was higher for 70% 1RM compared to 30% 1RM (P < 0.001), while the increase in muscle activation from the first to the last set (P < 0.001) occurred independently of altitude (P > 0.158). Deoxygenation and reoxygenation responses were higher under hypoxic versus normoxic conditions at 70% 1 RM (P = 0.013 and P = 0.015) but not 30% 1RM (P = 0.528 and P = 0.384). During upper-limb multi-set resistance exercise to failure, exposure to acute normobaric hypoxia negatively impacts performance at light, but not moderate, loads. Overall, external resistance has more profound effects on physiological strain than hypoxic exposure per se. Highlights The addition of acute systemic hypoxia negatively affects work performed at low, but not moderate, loads during upper-limb resistance exercise to failure. Hypoxic exposure, however, does not fundamentally alter muscle activation and oxygenation patterns. Muscle activation and oxygenation responses in turn are more largely influenced by load lifted. [ABSTRACT FROM AUTHOR]

With minimal costs and travel constraints for athletes, the “living low-training high” (LLTH) approach is becoming an important intervention for modern sport. The popularity of the LLTH model of altitude training is also associated with the fact that it only causes a slight disturbance to athletes' usual daily routine, allowing them to maintain their regular lifestyle in their home environment. In this perspective article, we discuss the evolving boundaries of the LLTH paradigm and its practical applications for athletes. Passive modalities include intermittent hypoxic exposure at rest (IHE) and Ischemic preconditioning (IPC). Active modalities use either local [blood flow restricted (BFR) exercise] and/or systemic hypoxia [continuous low-intensity training in hypoxia (CHT), interval hypoxic training (IHT), repeated-sprint training in hypoxia (RSH), sprint interval training in hypoxia (SIH) and resistance training in hypoxia (RTH)]. A combination of hypoxic methods targeting different attributes also represents an attractive solution. In conclusion, a growing number of LLTH altitude training methods exists that include the application of systemic and local hypoxia stimuli, or a combination of both, for performance enhancement in many disciplines.

Purposes: This study quantified performance, physiological, and perceptual responses during resistance exercise to task failure with blood flow restriction (BFR), in systemic hypoxia, and with these stimuli combined.Methods: Fourteen young men were tested for 1-repetition maximum (1RM) in the barbell biceps curl and lying triceps extension exercises. On separate visits, subjects performed exercise trials (4 sets to failure at 70% 1RM with 90 s between sets) in six separate randomized conditions, i.e., in normoxia or hypoxia (fraction of inspired oxygen = 20.9% and 12.9%, respectively) combined with three different levels of BFR (0%, 45%, or 60% of resting arterial occlusion pressure). Muscle activation and oxygenation were monitored via surface electromyography and near-infrared spectroscopy, respectively. Arterial oxygen saturation, heart rate, and perceptual responses were assessed following each set.Results: Compared to set 1, the number of repetitions before failure decreased in sets 2, 3, and 4 for both exercises (all P < 0.001), independently of the condition (P > 0.065). Arterial oxygen saturation was lower with systemic hypoxia (P < 0.001), but not BFR, while heart rate did not differ between conditions (P > 0.341). Muscle oxygenation and activation during exercise trials remained unaffected by the different conditions (all P ≥ 0.206). A significant main effect of time, but not condition, was observed for overall perceived discomfort, difficulty breathing, and limb discomfort (all P < 0.001).Conclusion: Local and systemic hypoxic stimuli, or a combination of both, did not modify the fatigue-induced change in performance, trends of muscle activation or oxygenation, nor exercise-related sensations during a multi-set resistance exercise to task failure. [ABSTRACT FROM AUTHOR]

Kosaku, Kazuhiro, Tomonori Harada, Toyoharu Jike, Isao Tsuboi, and Shin Aizawa. Long-term hypoxic tolerance in murine cornea. High Alt Med Biol 19:35–41, 2018. Aims: The cornea is believed to be an exceedingly sensitive organ to decreases in atmospheric oxygen concentrations. Previous corneal studies have shown the hypoxic tolerance of the cornea during short-term and local hypoxic exposure. This study investigated the tolerance of the cornea during long-term and systemic hypoxia. Methods and Results: Mice were bred under normobaric normoxia or hypoxia (10% oxygen concentration) conditions for 140 days. The layer structure, surface microvilli, and glycogen granules in the corneal epithelium were examined on day 2 and on day 140. The layer and surface structures of the corneal epithelium were normally maintained during the long-term hypoxia. Hypoxic stress caused a decrease in the glycogen granules in the corneal epithelial cells. Conclusions: Maintenance of normal structures during long-term hypoxia suggests that the cornea has a high tolerance for hypoxic stress. The quantity of glycogen in corneal epithelial cells is considered an index of corneal hypoxia resistance. [ABSTRACT FROM AUTHOR]

Omrani, Hasan, Mohammad Reza Alipour, Fereshteh Farajdokht, Hadi Ebrahimi, Mehran Mesgari Abbasi, and Gisou Mohaddes. Effects of chronic ghrelin treatment on hypoxia-induced brain oxidative stress and inflammation in a rat normobaric chronic hypoxia model. High Alt Med Biol. 18:145-151, 2017. Aim: This study aimed to evaluate the probable antioxidant effects of ghrelin in the brain and serum and its effect on tumor necrosis factor-alpha (TNF-α) levels in the brain in a model of chronic systemic hypoxia in rats. Methods: Systemic hypoxia was induced by a normobaric hypoxic chamber (O2 11%) for ten days. Adult male Wistar rats were divided into control (C), chronic ghrelin (80 μg/kg/10 days) (Ghr), chronic hypoxia (CH), and CH and ghrelin (80 μg/kg/ip/10 days) (CH + Gh) groups. The activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and malondialdehyde (MDA), total antioxidant capacity, and TNF-α levels were assessed in the serum and brain tissue. Results: Our results showed that chronic ghrelin administration attenuated the CH-increased oxidative stress by decreasing MDA levels in the serum and brain tissue. Moreover, ghrelin enhanced the antioxidant defense against hypoxia-induced oxidative stress in the serum and brain tissue. Brain TNF-α levels in CH did not change significantly; however, ghrelin significantly ( p < 0.001) decreased it. Conclusion: These results indicated that ghrelin promoted antioxidative and anti-inflammatory defense under chronic exposure to hypoxia. Therefore, ghrelin might be used as a potential therapy in normobaric hypoxia and oxidative stress induced by CH. [ABSTRACT FROM AUTHOR]

An epidemic scale of the breast cancer (BC) prevalence is actually recognised as the reality of the early twenty-first century. Particularly alarming is that the sporadic BC (about 90% of all patients) creates currently unpredictable subpopulations in terms of disease predisposition, development and progression. Despite broad discussions run since years in BC area, no any plausible approach has been suggested so far to get the overall situation better controlled in the populations. Here, we present highly innovative concepts considering investigation of specific syndromes and symptoms underestimated till now in relationship with BC predisposition and development. Consequently, the purpose of our pilot project was to evaluate the prevalence of Flammer Syndrome (FS) in BC patient cohort. The results achieved here support the main hypothesis of the project clearly demonstrating the tendency of BC patients to the increased prevalence of FS symptoms compared to the disease-free individuals. Our study strongly indicates the relevance of FS symptoms for BC pathology such as feeling inadequately cold, deficient thermoregulation, altered sensitivity to different stimuli, potential dehydration, altered sleep patterns, tendency towards headache, migraine attacks and dizziness. Moreover, the symptoms' appearance is specifically linked to the individual BC subtypes. Potential mechanisms interconnecting FS with BC pathology are discussed. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) epidemic in the twenty-first century is characterised by around half a million deaths and 1.7 million new cases registered annually worldwide. Metastatic disease is the major cause of death in BC patient cohorts. Current statistics are much alarming from the viewpoint of the early mortality amongst BC patients with de novo metastatic disease. A new paradigm of so-called 'pre-metastatic niches' may sufficiently promote our knowledge regarding potential pathomechanisms, individual predisposition and prognosis in development and progression of the metastatic disease. However, the crucial question remains unaddressed, whether hypoxic pre-metastatic niches in BC are created by or prior to the tumour onset. So far, the current interpretation of the 'Seed and Soil' theory of metastasis proposing that the pre-metastatic niches are formed by primary tumours which 'induce and guide' the process is incomplete, since it does not provide satisfactory explanations towards several facts overviewed in the article. The overall results of this study clearly support the working hypothesis presented by the authors proposing that the epi/genetic predisposition of individuals at risk to form the systemic hypoxic pre-metastatic niches can be established a long time before breast malignancy is clinically manifested. 'Flammer Syndrome' (FS) phenotype may strongly contribute to particularly poor outcomes of metastatic breast cancer. Significance and relevance of individual FS symptoms for breast cancer metastatic disease are discussed in extenso. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) epidemic is recognised now worldwide as the reality of the early twenty-first century. Increasing trends in the postmenopausal BC prevalence, even for the European countries earlier demonstrating relatively stable incidence rates of the disease, are highly alarming for the healthcare givers. This new actuality requires a substantial revision of the paradigm currently applied to the BC management and creation of highly innovative concepts. Current multi-centred study highlights new complex mechanisms of the development and progression of the postmenopausal BC. Innovative concepts are presented which argue for more effective predictive and preventive approaches well justified in view of the clusters of the symptoms analysed here and demonstrated as highly prevalent in the postmenopausal breast cancer versus BC-free individuals. Another conceptual novelty presented here is a new interpretation of the 'Seed and Soil' theory of metastasis in BC. According to the new concept, the 'pre-metastatic niches' ('Soil') are created by a systemic hypoxia a long time before the breast malignancy is clinically manifested. [ABSTRACT FROM AUTHOR]

Purpose: Diabetic retinopathy (DR) is a hypoxic retinal disease, but so far, the association with systemic hypoxia is poorly understood. Hence, the aim of this study was to evaluate cross-sectional and longitudinal associations between DR and chronic respiratory failure (CRF) in a national cohort., Design: Cross-sectional and 5-year longitudinal register-based cohort study., Methods: Between 2013 and 2018, we included patients with diabetes from the Danish Registry of Diabetic Retinopathy, who were each age and sex matched with five controls without diabetes. At index date, the prevalence of CRF was compared between cases and controls, and the longitudinal relationship between DR and CRF was assessed in a five-year follow-up., Results: At baseline, we identified 1,980 and 9,990 patients with CRF among 205,970 cases and 1,003,170 controls. The prevalence of CRF was higher among cases than controls (OR 1.75, 95% CI 1.65-1.86), but no difference between cases with and without DR was found.During follow-up, we identified 1,726 and 5,177 events of CRF among cases and controls, respectively. The incidence of CRF was higher among both cases with and without DR compared to controls (DR level 0: HR 1.24, 95% CI 1.16-1.33, DR level 1-4: HR 1.86, 95% CI 1.63-2.12), and higher among cases with DR compared to cases without DR (HR 1.54, 95% CI 1.38-1.72)., Conclusion: In this study based on nationwide data, we found an increased risk of present and incident CRF in patients with diabetes with or without DR, and we identified DR as a predictor of future CRF., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

Mast cells are immune cells of the myeloid lineage and are present in connective tissues throughout the body. The activation and degranulation of mast cells significantly modulates many aspects of physiological and pathological conditions in various settings. With respect to normal physiological functions, mast cells are known to regulate vasodilation, vascular homeostasis, innate and adaptive immune responses, angiogenesis, and venom detoxification. On the other hand, mast cells have also been implicated in the pathophysiology of many diseases including allergy, asthma, anaphylaxis, gastrointestinal disorders, many types of malignancies, and cardiovascular diseases. This review summarizes the current understanding of the role of mast cells in many pathophysiological conditions.

Objective To investigate the change of long-term behavior， brain morphology and myelin basic protein （MBP） expression after systematic hypoxia exposure in P0d neonatal rats. Methods P0d neonatal SD rats were randomly and equally divided into control group （NG group） and systematic hypoxia group （Hy group） . Hy group rats were exposed to 5%O2 for 3.5h. Behavior tests were applied at P29d and P30d. 1.5T MRI scanning of brain was used to detect morphology change in P60d rats after hypoxia. The changes in ultrastructure of hippocampal CA1 and corpus callosum （CC） after hypoxia were further confirmed by transmission electron microscopy （TEM）. Immunoblotting assays were performed to identify the dynamic changes of MBP. Results （1） The scores in refused captured test，open field test，slope experiments and the suspension test decreased （ < 0.05） . The success rates of Y arm maze test decreased and days up to standard significantly prolonged （ < 0.001） . （2） Abnormal signal in hippocampus and lateral ventricle， thinner corpus callosum were observed by 1.5T MRI scanning after hypoxia 2 months. （3） Electron microscope results revealed loosen structure and neuropil edema appeared in periventricular white matter. （4） The expression of MBP in the periventricular regions of NG group was detected by immunoblotting assay at the early development stages. Systemic hypoxia exposure to neonatal rats could decrease MBP expression after hypoxia 3 days but increase expression after hypoxia 4 hours （ < 0.05） . Conclusion An obviously morphology injury which distinct located in periventricular white matter （PWM） and the abnormal of the long-term behavior can be confirmed after systematic hypoxia exposure in neonatal rats. [ABSTRACT FROM AUTHOR]

Mast cells are immune cells of the myeloid lineage and are present in connective tissues throughout the body. The activation and degranulation of mast cells significantly modulates many aspects of physiological and pathological conditions in various settings. With respect to normal physiological functions, mast cells are known to regulate vasodilation, vascular homeostasis, innate and adaptive immune responses, angiogenesis, and venom detoxification. On the other hand, mast cells have also been implicated in the pathophysiology of many diseases, including allergy, asthma, anaphylaxis, gastrointestinal disorders, many types of malignancies, and cardiovascular diseases. This review summarizes the current understanding of the role of mast cells in many pathophysiological conditions. [ABSTRACT FROM AUTHOR]

Objective Sprint exercise and hypoxic stimulus during exercise are potent factors affecting hormonal and metabolic responses. However, the effects of different hypoxic levels on hormonal and metabolic responses during sprint exercise are not known. Here, we examined the effect of different hypoxic conditions on hormonal and metabolic responses during sprint exercise. Design Seven male subjects participated in three experimental trials: 1) sprint exercise under normoxia (NSE); 2) sprint exercise under moderate normobaric hypoxia (16.4% oxygen) (HSE 16.4); and 3) sprint exercise under severe normobaric hypoxia (13.6% oxygen) (HSE 13.6). The sprint exercise consisted of four 30 s all-out cycling bouts with 4-min rest between bouts. Glucose, free fatty acids (FFA), blood lactate, growth hormone (GH), epinephrine (E), norepinephrine (NE), and insulin concentrations in the HSE trials were measured before exposure to hypoxia (pre 1), 15 min after exposure to hypoxia (pre 2), and at 0, 15, 30, 60, 120, and 180 min after the exercise performed in hypoxia. The blood samples in the NSE trial were obtained in normoxia at the same time points as the HSE trials. Results Circulating levels of glucose, FFA, lactate, GH, E, NE, and insulin significantly increased after all three exercise trials (P < 0.05). The area under the curve (AUC) for GH was significantly higher in the HSE 13.6 trial than in the NSE and HSE 16.4 trials (P < 0.05). A maximal increase in FFA concentration was observed at 180 min after exercise and was not different between trials. Conclusion These findings suggest that severe hypoxia may be an important factor for the enhancement of GH response to all-out sprint exercise. [ABSTRACT FROM AUTHOR]

Acute kidney injury is a common complication of critically ill patients and may occur as a result of various factors and coexisting previous illnesses. Some pathophysiological responses seen in critical illness can be similar to the human physiological response to extreme environmental challenges, such as hypoxia from reduced oxygen availability at high altitudes (systemic hypoxia). Due to oxygen deficiency, mammalian cells activate the transcriptional factor hypoxia-inducible factor (HIF); its degradation is regulated by prolyl hydroxylase 3 (PHD3) in interaction with the scaffold protein MAPK organizer 1 (Morg1). While homozygous Morg1-/- mice are embryonically lethal, the kidneys of heterozygous Morg1+/- mice reveal elevated HIF protein levels and increased serum erythropoietin compared with wild-type Morg1+/+ mice. In this study, we exposed wild-type and Morg1+/- mice to 10% oxygen in a hypoxic chamber for 3 days. This reduced oxygen concentration leads to a deterioration of renal function, an increase in renal inflammation, and significantly more tubular damage and apoptosis in the kidneys of wild-type (Morg1+/+) mice. In sharp contrast, Morg1+/- kidneys were protected against systemic hypoxia. They show significantly less renal lesions, reduced or no inflammation, and less tubular damage and apoptosis. Thus short-term systemic and subsequently renal hypoxia which may occur in many patients in the intensive care unit induces in wild-type mice renal injury, which is ameliorated by Morg1 deficiency. Our findings suggest that therapeutical manipulation of Morg1 may be an interesting novel target to prevent hypoxiaassociated renal damage. [ABSTRACT FROM AUTHOR]

Hypoxia can be damaging either because cells are directly sensitive to low oxygen pressure in their local microenvironment and/or because they are exposed to circulating factors systemically secreted in response to hypoxia. The conventional hypoxia model, breathing hypoxic air, does not allow one to distinguish between these local and systemic effects. Here we propose and validate a model for differentially applying local and systemic hypoxic challenges in an animal. We used parabiosis, two mice sharing circulation by surgical union through the skin, and tested the hypothesis that when one of the parabionts breathes room air and the other one is subjected to hypoxic air, both mice share systemic circulation but remain normoxic and hypoxic, respectively. We tested two common hypoxic paradigms in 10 parabiotic pairs: continuous hypoxia (10% O2) mimicking chronic lung diseases, and intermittent hypoxia (40 s, 21% O2; 20 s, 5% O2) simulating sleep apnea. Arterial oxygen saturation and oxygen partial pressure at muscle tissue were measured in both parabionts. Effective cross-circulation was assessed by intraperitoneally injecting a dye in one of the parabionts and measuring blood dye concentration in both animals after 2 h. The results confirmed the hypothesis that tissues of the parabiont under room air were perfused with normally oxygenated blood and, at the same time, were exposed to all of the systemic mediators secreted by the other parabiont actually subjected to hypoxia. In conclusion, combination of parabiosis and hypoxic/normoxic air breathing is a novel approach to investigate the effects of local and systemic hypoxia in respiratory diseases. [ABSTRACT FROM AUTHOR]

Hypoxia is an important modulator of endurance exercise-induced oxidative adaptations in skeletal muscle. However, whether hypoxia affects resistance exercise-induced muscle adaptations remains unknown. Here, we determined the effect of resistance exercise training under systemic hypoxia on muscular adaptations known to occur following both resistance and endurance exercise training, including muscle cross-sectional area ( CSA), one-repetition maximum (1 RM), muscular endurance, and makers of mitochondrial biogenesis and angiogenesis, such as peroxisome proliferator-activated receptor- γ coactivator-1 α ( PGC-1 α), citrate synthase ( CS) activity, nitric oxide synthase ( NOS), vascular endothelial growth factor ( VEGF), hypoxia-inducible factor-1 ( HIF-1), and capillary-to-fiber ratio. Sixteen healthy male subjects were randomly assigned to either a normoxic resistance training group ( NRT, n = 7) or a hypoxic (14.4% oxygen) resistance training group ( HRT, n = 9) and performed 8 weeks of resistance training. Blood and muscle biopsy samples were obtained before and after training. After training muscle CSA of the femoral region, 1 RM for bench-press and leg-press, muscular endurance, and skeletal muscle VEGF protein levels significantly increased in both groups. The increase in muscular endurance was significantly higher in the HRT group. Plasma VEGF concentration and skeletal muscle capillary-to-fiber ratio were significantly higher in the HRT group than the NRT group following training. Our results suggest that, in addition to increases in muscle size and strength, HRT may also lead to increased muscular endurance and the promotion of angiogenesis in skeletal muscle. [ABSTRACT FROM AUTHOR]