Breathing Normoxic Air Research Articles

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.

Contribution of Carotid Bodies on Pulmonary Function During Normoxia and Acute Hypoxia.

Carotid bodies (CBs) are main peripheral chemoreceptors involved in breathing regulation. Despite the well-known role played by CBs on breathing control, the precise contribution of CBs on the regulation of lung mechanics remains controversial. Accordingly, we study changes in lung mechanics in normoxia (FiO2 21%) and hypoxia (FiO2 8%) in mice with or without functional CBs. For this, we used adult male mice that underwent sham or CB denervation (CBD) surgery. Compared to sham-operated mice, we found that CBD induced an increase in lung resistance (RL) while breathing normoxic air (sham vs. CBD, p<0.05). Importantly, changes in RL were accompanied by an approximately threefold reduction in dynamic compliance (Cdyn). Additionally, end-expiratory work (EEW) was increased in normoxia in the CBD group. Contrarily, we found that CBD has no effect on lung mechanics during hypoxic stimulation. Indeed, RL, Cdyn, and EEW values in CBD mice were undistinguishable from the ones obtained in sham mice. Finally, we found that CBD induces lung parenchyma morphological alterations characterized by reduced alveoli space. Together our results showed that CBD progressively increases lung resistance at normoxic conditions and suggest that CB tonic afferent discharges are needed for the proper regulation of lung mechanics at rest.

Pre-acclimation to altitude in young adults: choosing a hypoxic pattern at sea level which provokes significant haematological adaptations.

This single-blind, repeated measures study evaluated adaptive and maladaptive responses to continuous and intermittent hypoxic patterns in young adults. Changes in haematological profile, stress and cardiac damage were measured in ten healthy young participants during three phases: (1) breathing normoxic air (baseline); (2) breathing normoxic air via a mask (Sham-controls); (3) breathing intermittent hypoxia (IH) via a mask, mean peripheral oxygen saturation (SpO2) of 85% ~ 70min of hypoxia. After a 5-month washout period, participants repeated this three-phase protocol with phase, (4) consisting of continuous hypoxia (CH), mean SpO2 = 85%, ~ 70min of hypoxia. Measures of the red blood cell count (RBCc), haemoglobin concentration ([Hb]), haematocrit (Hct), percentage of reticulocytes (% Retics), secretory immunoglobulin A (S-IgA), cortisol, cardiac troponin T (cTnT) and the erythropoietic stimulation index (calculated OFF-score) were compared across treatments. Despite identical hypoxic durations at the same fixed SpO2, no significant effects were observed in either CH or Sham-CH control, compared to baseline. While IH and Sham-IH controls demonstrated significant increases in: RBCc; [Hb]; Hct; and the erythropoietic stimulation index. Notably, the % Retics decreased significantly in response to IH (-31.9%) or Sham-IH control (-23.6%), highlighting the importance of including Sham-controls. No difference was observed in S-IgA, cortisol or cTnT. TheIH but not CH pattern significantly increased key adaptive haematological responses, without maladaptive increases in S-IgA, cortisol or cTnT, indicating that the IH hypoxic pattern would be the best method to boost haematological profiles prior to ascent to altitude.

Cutaneous Vascular Responses of the Hands and Feet to Cooling, Rewarming, and Hypoxia in Humans

This study investigated skin vasomotor responses in the fingers and toes during cooling and rewarming with and without normobaric hypoxia. Fourteen volunteers (8 males and 6 females) were exposed to gradual air cooling (mean±SD: -0.4±0.1oC·min-1) followed by rewarming (+0.5±0.1oC·min-1) while breathing normoxic air (FIO2 0.21 at 761±3 mm Hg) or hypoxic gas (FIO2 0.12, at 761±3 mm Hg, equivalent to ~5000 m above sea level). Throughout the gradual cooling and rewarming phases, rectal temperature was measured, and skin temperatures and laser Doppler skin blood flow were measured on the thumb, little finger, and great and little toe pads. During gradual cooling, skin temperature but not deep body temperature decreased. No differences in cutaneous vascular conductance were found for the toes or thumb (P=0.169 great toe; P=0.289 little toe; P=0.422 thumb). Cutaneous vascular conductance was reduced in the little finger to a greater extent at the same mean skin temperatures (34.5-33.5oC) in the hypoxic compared with normoxic conditions (P=0.047). The onset of vasoconstriction and release of vasoconstriction in the thumb and little finger occurred at higher mean skin temperatures in hypoxia compared with normoxia (P<0.05). The onset of vasoconstriction and release of vasoconstriction in the toes occurred at similar skin temperatures (P=0.181 and P=0.132, respectively). The earlier vasoconstrictor response and later release of vasoconstriction in the finger during hypoxic conditions may result in a greater dose of cold to that digit, taking longer to rewarm following the release of vasoconstriction.

Normoxic Recovery Mimicking Treatment of Sleep Apnea Does Not Reverse Intermittent Hypoxia-Induced Bacterial Dysbiosis and Low-Grade Endotoxemia in Mice.

Intermittent hypoxia (IH) mimicking obstructive sleep apnea (OSA) significantly modifies gut microbiota in mice. However, whether these IH-induced gut microbiome changes are reversible after restoring normal oxygenation (the equivalent of effective OSA therapy) is unknown. The aim of this study was to investigate gut microbiota composition and circulating endotoxemia after a post-IH normoxic period in a mouse model of OSA. Ten mice were subjected to IH (40 sec 21% O2-20 sec 5% O2) for 6 h/day for 6 w and 10 mice breathing normoxic air (NM) were used as controls. After exposures, both groups were subjected to 6 w in normoxia. Microbiome composition of fecal samples was determined by 16S ribosomal RNA (rRNA) pyrosequencing. Bioinformatic analysis was performed by Quantitative Insights into Microbial Ecology. Plasma lipopolysaccharide (LPS) levels were measured by endotoxin assay. After normoxic recovery, the Chao and Shannon indices of each group suggested similar bacterial richness and diversity. 16S rRNA pyrosequencing analysis showed that IH-exposed mice had a significant decrease in the abundance of Bacteroidetes and a significant increase of Firmicutes and Deferribacteres compared to the NM group. After normoxic recovery, circulating LPS concentrations were higher in the IH group (P < 0.009). Moreover, the IH group showed a negative and significant correlation between the abundance of Lactobacillus and Ruminococcus and significant positive correlations between the abundance of Mucispirillum and Desulfovibrio and plasma LPS levels, respectively. Even after prolonged normoxic recovery after IH exposures, gut microbiota and circulating endotoxemia remain negatively altered, suggesting that potential benefits of OSA treatment for reversing OSA-induced changes in gut microbiota may either require a longer period or alternative interventions.

Effect of Inhaled Nitric Oxide on Exercise Capacity and Pulmonary Gas Exchange in Adult Survivors of Preterm Birth

RATIONALEPreterm birth affects millions of infants each year, and survival rates are on the rise. Frequently, premature birth results in alveolar simplification that may persist into adulthood. We have previously shown that pulmonary gas exchange efficiency is lower during exercise in some adults born preterm compared with control subjects. However, it is unknown whether the presence of inhaled nitric oxide (iNO), a potent broncho‐ and vasodilator, has an effect on pulmonary gas exchange and other physiological measures during exercise in preterm birth survivors. The objective of this study was to determine the effect of iNO on alveolar to arterial oxygen difference (AaO2), respiratory exchange ratio (RER), and maximum wattage during exercise in adult survivors of preterm birth.METHODSFourteen young adults born preterm (recruited from the Newborn Lung Project, birth weight &lt;1,500 g, gestational age &lt;36wk, age 20–23 years) and 16 term‐born, age‐matched control subjects performed incremental exercise on a cycle ergometer to volitional exhaustion while breathing normoxic air with and without iNO. Arterial and venous blood samples were taken every two minutes. Ventilation, mixed expired gases, power output, and oxygen consumption were continuously measured during rest and exercise using LabChart. Max wattage, RER, and AaO2 were calculated. Statistics were done with two‐way ANOVA to compare control and preterm with and without iNO with Tukey's for multiple comparisons.RESULTSWith respect to max power, controls attained a higher wattage than preterms in normoxia (p= 0.01). This difference was attenuated in the presence of iNO (174.3 ± 28.4 W controls without iNO v 141.4 ± 27.2 W preterms with iNO, p = 0.21). With respect to RER, there was no significant difference between controls and preterms in normoxia. In the presence of iNO, preterms had a significantly higher RER than controls without iNO throughout graded exercise (0.92 ± 0.10 v 0.89 ± 0.12, p = 0.0013). Preterms had a significantly higher AaO2 than controls during graded exercise in normoxia without iNO, which was attenuated with iNO (9.3 ±6.1 mmHg control v 11.6 ±10.8 mmHg preterm, p =0.21).CONCLUSIONSWe have previously shown that pulmonary gas exchange efficiency is lower in some adult survivors of preterm birth during exercise compared with control subjects. Here we show that iNO in preterm adults attenuates many of the metabolic and pulmonary gas exchange differences between preterm and control adults during graded exercise, including AaO2 and max power. RER in the preterm + NO group was significantly higher than the controls without NO. Overall, this suggests iNO can improve gas exchange efficiency in preterm born young adults.Support or Funding InformationNIH NHLBI, R01 HL086897 (Eldridge)Nitric oxide was supplied by Mallinckrodt Pharmaceuticals, formerly Ikaria, Inc.

When Posture is Controlled, Acute Hypoxia does not Decrease Core Temperature

It has been reported that acute hypoxia causes a reduction in core temperature in humans. It was hypothesized that this occurs due to both a decrease in metabolic rate and an increase in skin blood flow. However, other studies have found that core temperature decreases with changes in posture. The methods in previous studies finding hypoxia to decrease core temperature did not control for postural changes. Thus, further examination is warranted to examine the effect of hypoxia on core temperature while controlling for posture change. Ten healthy adults, between the ages of 18 and 45 were recruited to participate. Subjects completed one trial consisting of breathing normoxic air (20.9%) for a 2 hour period and hypoxic air for a 1 hour period, while systematically changing posture. During this time core temperature and skin blood flow were recorded every 5 minutes. The results showed that mean core body temperature significantly (p < 0.05) decreased by 0.4℃ when the subjects transitioned from a standing to lying position. However, acute hypoxia, which reduced the mean oxygen saturation to 85%, did not significantly affect core temperature. Such results suggest that when posture is controlled, acute hypoxia does not significantly decrease core body temperature. Thus, the results of previous studies that have reported decreases in core temperature with acute hypoxia, but failed to control for posture, need to be questioned.

Effects of Low-Intensity Resistance Exercise Under Acute Systemic Hypoxia on Hormonal Responses

Previous studies have shown that low-intensity resistance exercises with vascular occlusion and slow movement effectively increase muscular size and strength. Researchers have speculated that local hypoxia by occlusion and slow movement may contribute to such adaptations via promoting anabolic hormone secretions by the local accumulation of metabolites. In this study, we determined the effects of low-intensity resistance exercise under acute systemic hypoxia on metabolic and hormonal responses. Eight male subjects participated in 2 experimental trials: (a) low-intensity resistance exercise while breathing normoxic air (normoxic resistance exercise [NR]), (b) low-intensity resistance exercise while breathing 13% oxygen (hypoxic resistance exercise [HR]). The resistance exercises (bench press and leg press) consisted of 14 repetitions for 5 sets at 50% of maximum strength with 1 minute of rest between sets. Blood lactate (LA), serum growth hormone (GH), norepinephrine (NE), testosterone, and cortisol concentrations were measured before normoxia and hypoxia exposures; 15 minutes after the exposures; and at 0, 15, and 30 minutes after the exercises. The LA levels significantly increased after exercises in both trials (p ≤ 0.05). The area under the curve for LA after exercises was significantly higher in the HR trial than in the NR trial (p ≤ 0.05). The GH significantly increased only after the HR trial (p ≤ 0.05). The NE and testosterone significantly increased after the exercises in both trials (p ≤ 0.05). Cortisol did not significantly change in both trials. These results suggest that low-intensity resistance exercise in the hypoxic condition caused greater metabolic and hormonal responses than that in the normoxic condition. Coaches may consider low-intensity resistance exercise under systemic hypoxia as a potential training method for athletes who need to maintain muscle mass and strength during the long in-season.

Effects of Acute Hypoxia on Metabolic and Hormonal Responses to Resistance Exercise

Several recent studies have shown that resistance exercise combined with vascular occlusion effectively causes increases in muscular size and strength. Researchers speculated that the vascular occlusion-induced local hypoxia may contribute to the adaptations via promoting anabolic hormone secretions stimulated by local accumulation of metabolic subproducts. Here, we examined whether acute systemic hypoxia affects metabolic and hormonal responses to resistance exercise. Twelve male subjects participated in two experimental trials: 1) resistance exercise while breathing normoxic air [normoxic resistance exercise (NR)] and 2) resistance exercise while breathing 13% oxygen [hypoxic resistance exercise (HR)]. The resistance exercises (bench press and leg press) consisted of 10 repetitions for five sets at 70% of maximum strength with 1-min rest between sets. Blood lactate, serum growth hormone (GH), epinephrine (E), norepinephrine (NE), insulin-like growth factor 1, testosterone, and cortisol concentrations were measured before normoxia and hypoxia exposures, 15 min after the exposures, and at 0, 15, 30, and 60 min after the exercises. Lactate significantly increased after exercises in both trials (P < 0.05). In the HR trial, GH and cortisol significantly increased after the exercise (P < 0.05) but not in the NR trial. The E, NE, insulin-like growth factor 1, and testosterone significantly increased after the exercises in both trials (P < 0.05). The mean values of lactate, GH, E, and NE after exercises were significantly higher in the HR trial than those in the NR trial (P < 0.05). These findings suggest that resistance exercise in hypoxic condition caused greater accumulation of metabolites and strong anabolic hormone response.

Ventilatory Support During Exercise in Patients With Pulmonary Tuberculosis Sequelae

The aim of this study was to determine whether intermittent positive pressure ventilation through a nasal mask (NIPPV) applied during exercise in patients with pulmonary tuberculosis sequelae (PTS) could improve arterial blood gas measurements, ameliorate breathlessness, and increase exercise endurance. Seven PTS patients with a severe restrictive ventilatory defect (mean [SD] vital capacity, 1.02 [0.25] I) enrolled in this study had experienced NIPPV previously, and were familiar with the procedure. The patients underwent four constant-load cycle ergometer tests in the supine position to tolerance. The tests were performed with and without NIPPV, while breathing normoxic air (Air) or supplemental oxygen (O2; 35%). NIPPV was delivered during exercise in a controlled, volume-cycled mechanical ventilation mode, and the ventilator settings were modulated manually to meet patients' respiratory demands as estimated from the airway pressure waveform and the patient's breathlessness. All patients matched their breathing to the ventilator cycle during most of the exercise while receiving NIPPV. NIPPV significantly prolonged their exercise endurance time, from a mean (SD) of 180 (58) s to 310 (96) s in Air, and from 227 (64) s to 465 (201) s in O2. During exercise, NIPPV effectively decreased their breathlessness and significantly improved arterial blood gas measurements. NIPPV applied during exercise can effectively support ventilation, significantly ameliorate breathlessness, and consequently improve exercise endurance in patients with PTS.

Oxygen Supplementation during Exercise in Cystic Fibrosis

Fourteen female and 22 male patients with cystic fibrosis (CF), 8 to 29 yr of age, performed two progressive exercise tests to exhaustion on a cycle ergometer, breathing normoxic air (21% O2) for one test, and hyperoxic air (30% O2) for the other test. The order of gas administration was randomized. Minute ventilation (VE), oxygen uptake (VO2), end-tidal CO2 tension (PETCO2), work rate, oxyhemoglobin saturation (SAO2), and heart rate (HR) were measured throughout the tests. The SaO2 of 11 patients at peak exercise was 90% or less ("Low Sat" group). The SaO2 of 23 patients remained above 90% throughout the exercise ("High Sat" group). Hyperoxic air minimized desaturation during exercise in the Low Sat group to 2 +/- 2% compared to a decrease of 10 +/- 5% with normoxic air. The decrease in saturation was not significant for the High Sat group (1 +/- 1% for both 21% and 30% O2). Peak work rate and VO2 did not differ significantly between normoxic and hyperoxic conditions. However, VE and HR at peak exercise tended to be lower, and PETCO2 was higher during peak exercise with 30% O2 than 21% O2 for both groups. During submaximal exercise, O2 desaturation was diminished and HR was significantly lower with supplemental O2, specifically in the Low Sat group. VE was significantly lower for both groups during submaximal exercise with hyperoxic air. The results suggest that O2 supplementation minimizes O2 desaturation and enables patients with CF to exercise with reduced ventilatory and cardiovascular work.

Respiration of the emersed shore crab at variable ambient oxygenation

In the intertidal shore crab,Carcinus maenas, pH and $$P_{CO_2 } $$ values of the prebranchial venous hemolymph, $${\text{p}}H\bar v$$ and $$P\bar v_{CO_2 } $$ , the PO2 values of the arterialized cardiac hemolymph, $$P{\text{a}}_{O_2 } $$ , were measured, and the ventilatory activity was assessed by measuring the hydrostatic pressures at the exits of the epibranchial cavities, under four environmental conditions: normoxic water, normoxic air, hypoxic gas, hyperoxic gas. In the crab breathing normoxic air, $$P{\text{a}}_{O_2 } $$ was lower and $$P\bar v_{CO_2 } $$ higher than in animals breathing normoxic water. With the switch to hypoxic gas, ventilation increased and $$P{\text{a}}_{O_2 } $$ and $$P\bar v_{CO_2 } $$ decreased. With the switch to hyperoxic gas, ventilation decreased, $$P{\text{a}}_{O_2 } $$ and $$P\bar v_{CO_2 } $$ increased and $${\text{p}}H\bar v$$ decreased. Thus these crabs breathing air were not as well oxygenated as when breathing air-equilibrated water, and because of their low $$P{\text{a}}_{O_2 } $$ , they were relatively hypervetilating and hypocapnic compared to air-breathing vertebrates. Hyperoxic breathing, increasing $$P{\text{a}}_{O_2 } $$ and reducing ventilatory drive, led to increased $$P\bar v_{CO_2 } $$ . Conversely, $$P\bar v_{CO_2 } $$ was reduced by hypoxic breathing. These observations suggest that the gas exchanger of intertidal crabs is not as successfully designed for air breathing as that of land-colonizing insects and air-breathing vertebrates.