Effect of progressive normobaric hypoxia on dynamic cerebral autoregulation.

NEW FINDINGS: What is the central question of this study? Acute hypoxia reduces dynamic cerebral autoregulation (dCA); however, it is unclear what level of hypoxia is necessary to exert this effect. We sought to investigate whether dCA would be reduced during progressive periods of normobaric hypoxia using a duplex Doppler ultrasound technique to evaluate the volumetric blood flow. What is the main finding and its importance? We showed that dCA decreased linearly as inspired O2 decreased from 21 to 12%. Additionally, symptoms of acute mountain sickness were related to changes in dCA. Our results may provide a sensitive and clinically relevant test to evaluate the risk of acute mountain sickness. Cerebral blood flow is maintained at relatively constant levels over a wide range of perfusion pressures via cerebral autoregulation (CA). Although acute hypoxia reduces dynamic CA, it is unclear what level of hypoxia is necessary to exert this effect. We evaluated dynamic CA during progressive normobaric hypoxia (∼1 h at each of 21, 18, 15 and 12% O2 ) using duplex ultrasonography to measure volumetric changes in common carotid artery blood flow of 11 healthy young men. Dynamic CA was evaluated by the thigh-cuff method and represented as the rate of regulation of vascular conductance. On a separate occasion, symptoms of acute mountain sickness were evaluated during 6 h of prolonged hypoxia (fractional inspired O2 of 14.1%) using the Lake Louise Questionnaire. Repeated-measures ANOVA with linear trend analysis indicated that dynamic CA decreased progressively as fractional inspired O2 was reduced (P < 0.001). Spearman rank order analysis revealed that symptoms of acute mountain sickness were related to changes in the rate of regulation of vascular conductance from 21 to 15% (r = -0.869, P = 0.006) and from 21 to 12% O2 (r = -0.648, P = 0.040), respectively. These results suggest that dynamic CA worsens with progressive hypoxia and that reductions in dynamic CA during moderate to severe hypoxia (<15% O2 ) may be related to the severity of acute mountain sickness.

Reduction in Cerebral Oxygenation After Prolonged Exercise in Hypoxia is Related to Changes in Blood Pressure.

We investigated the relation between blood pressure and cerebral oxygenation (COX) immediately after exercise in ten healthy males. Subjects completed an exercise and recovery protocol while breathing either 21% (normoxia) or 14.1% (hypoxia) O2 in a randomized order. Each exercise session included four sets of cycling (30 min/set, 15 min rest) at 50% of altitude-adjusted peak oxygen uptake, followed by 60 min of recovery. After exercise, mean arterial pressure (MAP; 87±1 vs. 84±1 mmHg, average values across the recovery period) and COX (68±1% vs. 58±1%) were lower in hypoxia compared to normoxia (P<0.001). Changes in MAP and COX were correlated during the recovery period in hypoxia (r=0.568, P<0.001) but not during normoxia (r=0.028, not significant). These results demonstrate that reductions in blood pressure following exercise in hypoxia are (1) more pronounced than in normoxia, and (2) associated with reductions in COX. Together, these results suggest an impairment in cerebral autoregulation as COX followed changes in MAP more passively in hypoxia than in normoxia. These findings could help explain the increased risk for postexercise syncope at high altitude.

Reference range of blood biomarkers for oxidative stress in Thoroughbred racehorses (2-5 years old).

The oxidant and antioxidant equilibrium is known to play an important role in equine medicine and equine exercise physiology. There are abundant findings in this field; however, not many studies have been conducted for reference ranges of oxidative stress biomarkers in horses. This study was conducted to determine the reference values of reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP) using blood samples from 372 (191 males, 181 females) Thoroughbred racehorse aged 2 to 5 (3.43 ± 1.10 (mean ± SD)) years old. There were obvious gender differences in oxidative biomarkers, and growth/age-related changes were observed especially in females. Gender and age must be considered when interpreting obtained oxidative stress biomarkers for diagnosis of disease or fitness alterations in Thoroughbred racehorses.

High-intensity exercise causes greater irisin response compared with low-intensity exercise under similar energy consumption.

Irisin is mainly released from skeletal muscle (myocytes) and promotes thermogenesis by browning of the white adipose tissue. Although exercise has been shown to increase irisin concentration in blood and myocytes via up-regulation peroxisome proliferator receptor γ coactivator-1α (PGC-1α) expression, the influence of exercise intensity on irisin secretion remains unclear. Therefore, we determined circulating irisin responses following a single bout of running at different intensities. Six sedentary males underwent treadmill running under two different conditions: a low-intensity (40% of VO2max) exercise trial (LIE) or a high-intensity (80% of VO2max) exercise trial (HIE). The exercises in LIE and HIE were lasted for 20 and 40 min, respectively. All subjects underwent the two trials on separate days, and a randomized cross-over design was used. Blood samples were collected before (Pre) and immediately after exercise, at 3, 6, and 19 h after exercise. Energy consumption during exercise did not significantly differ between the two trials. HIE significantly increased blood lactate and serum lactate dehydrogenase levels (P < 0.05). Compared with pre-exercise levels, the irisin concentrations were elevated at 6 h (18% increase) and 19 h (23% increase) after HIE, but significantly decreased after LIE. The relative irisin concentrations (compared with pre-exercise levels) were significantly greater in HIE than in LIE immediately after exercise, and at 6 and 19 h after exercise (P < 0.05). These findings suggest that irisin secretion after acute running exercise is affected by exercise intensity, independent of energy consumption.

Influence of short-term hypoxic exposure on spatial learning and memory function and brain-derived neurotrophic factor in rats-A practical implication to human's lost way.

The present study aimed to investigate the effects of a short period of normobaric hypoxic exposure on spatial learning and memory, and brain-derived neurotrophic factor (BDNF) levels in the rat hippocampus. Hypoxic conditions were set at 12.5% O2. We compared all variables between normoxic trials (Norm), after 24 h (Hypo-24 h), and after 72 h of hypoxic exposure (Hypo-72 h). Spatial learning and memory were evaluated by using a water-finding task in an open field. Time to find water drinking fountains was significantly extended in Hypo 24 h (36.2 ± 21.9 s) compared to those in Norm (17.9 ± 12.8 s; P < 0.05), whereas no statistical differences between Norm and Hypo-72 h (22.7 ± 12.3 s). Moreover, hippocampal BDNF level in Hypo-24 h was significantly lower compared to Norm (189.4 ± 28.4 vs. 224.9 ± 47.7 ng/g wet tissue, P < 0.05), whereas no statistically differences in those between Norm and Hypo-72 h (228.1 ± 39.8 ng/g wet tissue). No significant differences in the changes in corticosterone and adrenocorticotropic hormone levels were observed across the three conditions. When data from Hypo-24 h and Hypo-72 h of hypoxia were pooled, there was a marginal negative relationship between the time to find drinking fountains and BDNF (P < 0.1), and was a significant negative relationship between the locomotor activities and BDNF (P < 0.05). These results suggest that acute hypoxic exposure (24 h) may impair spatial learning and memory; however, it recovered after 72 h of hypoxic exposure. These changes in spatial learning and memory may be associated with changes in the hippocampal BDNF levels in rats.

Hypoxic-induced resting ventilatory and circulatory responses under multistep hypoxia is related to decline in peak aerobic capacity in hypoxia.

BACKGROUND: Several factors have been shown to contribute to hypoxic-induced declined in aerobic capacity. In the present study, we investigated the effects of resting hypoxic ventilatory and cardiac responses (HVR and HCR) on hypoxic-induced declines in peak oxygen uptake ([Formula: see text]O2peak). METHODS: Peak oxygen uptakes was measured in normobaric normoxia (room air) and hypoxia (14.1% O2) for 10 young healthy men. The resting HVR and HCR were evaluated at multiple steps of hypoxia (1 h at each of 21, 18, 15 and 12% O2). Arterial desaturation (ΔSaO2) was calculate by the difference between SaO2 at normoxia-at each level of hypoxia (%). HVR was calculate by differences in pulmonary ventilation between normoxia and each level of hypoxia against ΔSaO2 (L min-1 %-1 kg-1). Similarly, HCR was calculated by differences in heart rate between normoxia and each level of hypoxia against ΔSaO2 (beats min-1 %-1). RESULTS: [Formula: see text]O2peak significantly decreased in hypoxia by 21% on average (P < 0.001). HVR was not associated with changes in [Formula: see text]O2peak. ΔSaO2 from normoxia to 18% or 15% O2 and HCR between normoxia and 12% O2 were associated with changes in [Formula: see text]O2peak (P < 0.05, respectively). The most optimal model using multiple linear regression analysis found that ΔHCR at 12% O2 and ΔSaO2 at 15% O2 were explanatory variables (adjusted R2 = 0.580, P = 0.02). CONCLUSION: These results suggest that arterial desaturation at moderate hypoxia and heart rate responses at severe hypoxia may account for hypoxic-induced declines in peak aerobic capacity, but ventilatory responses may be unrelated.

The effects of ingestion of hydrogen-dissolved alkaline electrolyzed water on stool consistency and gut microbiota: a double-blind randomized trial.

A relationship between Bifidobacterium and defecation has previously been reported. Our hypothesis on the effectiveness of alkaline electrolyzed water (AEW) proposes that ingestion of AEW, considered possessing antioxidative properties, increases the number of Bifidobacteria and improves stool hardness and gastrointestinal symptoms. A double-blind, randomized study was conducted to evaluate the connection between stool consistency and change in gut microbiota composition induced by drinking hydrogen-dissolved AEW. The participants drank 500 mL of purified tap water or AEW every day for 2 weeks. In this study, drinking AEW did not drastically change gut microbiota, but it appeared to act on a specific bacterial species. Drinking AEW was confirmed to cause an increase in Bifidobacterium. The AEW group also saw stool consistency significantly converge to Bristol stool scale Type 4 ("normal"). Therefore, it is highly likely that the gut microbiota will be changed by drinking AEW. This study was retrospectively registered in University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN ID: UMIN000039507) on February 18, 2020, and was approved by the Ethics Committee of University of Yamanashi (approval No. H30-25) on January 9, 2018.

Impact of Dietary Nitrate Supplementation on Executive Function During Hypoxic Exercise.

We investigated the effects of 4-day dietary beetroot (BR) juice supplementation on executive function assessed by color-word Stroop task (CWST) in hypoxia (fraction of inspired oxygen [FiO2] = 0.1395). Eight healthy young men performed 25-minute leg cycling exercise (target heart rate, 140 bpm) randomly with placebo (PL) juice or BR supplementation. The CWST was evaluated at resting hypoxic condition (after 30 minutes of hypoxic exposure) and at 15 minutes during exercise. During exercise, the correct response time in the CWST was significantly shortened compared with those at rest with no differences between PL and BR. The response accuracy in the CWST with BR was marginally lower than that with PL during exercise (p = 0.066). There were no significant differences in all physiological values, including pulmonary ventilation, arterial oxygen saturation, partial pressure of end-tidal carbon dioxide output, and tissue oxygenation in the left frontal lobe, assessed by near-infrared spectroscopy during exercise conditions involving PL and BR supplementation. These results suggest that moderate exercise in hypoxia partially improved executive function; however, 4-day dietary BR supplementation did not improve executive function during hypoxic exercise.

Muscle oxygenation profiles between active and inactive muscles with nitrate supplementation under hypoxic exercise.

Whether dietary nitrate supplementation improves exercise performance or not is still controversial. While redistribution of sufficient oxygen from inactive to active muscles is essential for optimal exercise performance, no study investigated the effects of nitrate supplementation on muscle oxygenation profiles between active and inactive muscles. Nine healthy males performed 25 min of submaximal (heart rate ~140 bpm; EXsub) and incremental cycling (EXmax) until exhaustion under three conditions: (A) normoxia without drink; (B) hypoxia (FiO2 = 13.95%) with placebo (PL); and (c) hypoxia with beetroot juice (BR). PL and BR were provided for 4 days. Oxygenated and deoxygenated hemoglobin (HbO2 and HHb) were measured in vastus lateralis (active) and biceps brachii (inactive) muscles, and the oxygen saturation of skeletal muscle (StO2; HbO2/total Hb) were calculated. During EXsub, BR suppressed the HHb increases in active muscles during the last 5 min of exercise. During EXmax, time to exhaustion with BR (513 ± 24 sec) was significantly longer than with PL (490 ± 39 sec, P < 0.05). In active muscles, BR suppressed the HHb increases at moderate work rates during EXmax compared to PL (P < 0.05). In addition, BR supplementation was associated with greater reductions in HbO2 and StO2 at higher work rates in inactive muscles during EXmax Collectively, these findings indicate that short-term dietary nitrate supplementation improved hypoxic exercise tolerance, perhaps, due to suppressed increases in HHb in active muscles at moderate work rates. Moreover, nitrate supplementation caused greater reductions in oxygenation in inactive muscle at higher work rates during hypoxic exercise.

Cognitive Function and Cerebral Oxygenation During Prolonged Exercise Under Hypoxia in Healthy Young Males.

Dobashi, Shohei, Masahiro Horiuchi, Junko Endo, Masataka Kiuchi, and Katsuhiro Koyama. Cognitive function and cerebral oxygenation during prolonged exercise under hypoxia in healthy young males. High Alt Med Biol. 17:214-221, 2016.-The present study examined the effect of prolonged hypoxic exercise on cognitive function. Eight healthy male volunteers were required to complete exercise trials (four 30-minute cycling sessions with a 15-minute rest interval) at an intensity corresponding to 50% of their altitude-adjusted peak oxygen uptake under two different conditions: normoxia (room air at 400 m) and hypoxia (fraction of inspired oxygen: 0.141). Cognitive function was evaluated before, during, and 60 minutes after completion of the exercise trial. The color-word Stroop task (CWST) was used to assess cognitive function, with regard to the number of achievements, accuracy rate, and the number of correct responses made within 60 seconds. Cerebral oxygenation was monitored throughout the experimental period using near-infrared spectroscopy. The accuracy rate did not significantly differ between the two trials. A significant reduction in the number of correct responses during simple CWST tasks was detected in the hypoxic condition 60 minutes after exercise (p < 0.05), wherein a significant correlation was identified between reduced task performance on simple CWST and cerebral oxygenation (p < 0.01). These results demonstrate that prolonged exercise under hypoxic conditions induces a reduction in cerebral oxygenation partly associated with impairment of cognitive function.

Intravenous infusion of H2-saline suppresses oxidative stress and elevates antioxidant potential in Thoroughbred horses after racing exercise.

Upon intensive, exhaustive exercise, exercise-induced reactive oxygen species may exceed the antioxidant defence threshold, consequently resulting in muscular damage or late-onset chronic inflammation. Recently, the therapeutic antioxidant and anti-inflammatory effects of molecular hydrogen (H2) for human rheumatoid arthritis have been demonstrated. However, it is also important to clarify the effects of administrating H2 in large animals other than humans, as H2 is thought to reach the target organ by passive diffusion upon delivery from the blood flow, indicating that the distance from the administration point to the target is critical. However, data on the effects of H2 on oxidative stress in real-life exhaustive exercise in large animals are currently lacking. We here investigated 13 Thoroughbred horses administered intravenous 2-L saline with or without 0.6-ppm H2 (placebo, N = 6; H2, N = 7) before participating in a high-intensity simulation race. Intravenous H2-saline significantly suppressed oxidative stress immediately, 3 h, and 24 h after the race, although the antioxidant capability was not affected throughout the study. The serum creatine kinase, lactate, and uric acid levels were increased in both groups. Taken together, these results indicate that intravenous H2-saline can significantly and specifically suppress oxidative stress induced after exhaustive racing in Thoroughbred horses.