Acute Exposure to Simulated High-altitude Hypoxia Alters Gut Microbiota in Mice

Gut microbiota bears adaptive potential to different environments, but little is known regarding its responses to acute high-altitude exposure. This study aimed to evaluate the microbial changes after acute exposure to simulated high-altitude hypoxia. C57BL/6J mice were divided into hypoxia and normoxia groups. The hypoxia group was exposed to a simulated altitude of 5500 m for 24 hours above sea level. The normoxia group was maintained in low-altitude of 10 m above sea level. Colonic microbiota was analyzed using 16S rRNA V4 gene sequencing. Compared with the normoxia group, shannon, simpson and Akkermansia were significantly increased, while Firmicutes to Bacteroidetes ratio and Bifidobacterium were significantly decreased in the hypoxia group. The hypoxia group exhibited lower mobile element containing and higher potentially pathogenic and stress tolerant phenotypes than those in the normoxia group. Functional analysis indicated that environmental information processing was significantly lower, metabolism, cellular processes and organismal systems were significantly higher in the hypoxia group than those in the normoxia group. In conclusion, acute exposure to simulated high-altitude hypoxia alters gut microbiota diversity and composition, which may provide a potential target to alleviate acute high-altitude diseases.

Effects of simulated high altitude on blood glucose levels during exercise in individuals with Type 1 Diabetes

Context Current exercise guidelines for individuals with type 1 diabetes (T1D) do not consider the impact that high altitude may have on blood glucose levels (BGL) during exercise. Objective To investigate the effect of acute hypoxia (simulated high altitude) on BGL and carbohydrate oxidation rates during moderate intensity exercise in individuals with T1D. Methods Using a counterbalanced, repeated measures study design, 7 individuals with T1D completed two exercise sessions; normoxia and hypoxia (~4,200m simulated altitude). Participants cycled for 60min on an ergometer at 45% of their sea-level V̇O2peak, and then recovered for 60min. Before, during and after exercise, blood samples were taken to measure glucose, lactate and insulin levels. Respiratory gases were collected to measure carbohydrate oxidation rates. Results Early during exercise (<30min), there was no fall in BGL in either condition. After one hour of exercise and during recovery, BGL were significantly lower under the hypoxic condition compared to both pre-exercise levels (p=0.008) and the normoxic condition (p=0.027). Exercise in both conditions resulted in a significant rise in carbohydrate oxidation rates, which returned to baseline levels post-exercise. Before, during and after exercise, carbohydrate oxidation rates were higher under the hypoxic compared with the normoxic condition (p<0.001). Conclusions The greater decline in BGL during and after exercise performed under acute hypoxia suggests that exercise during acute exposure to high altitude may increase the risk of hypoglycemia in individuals with T1D. Future guidelines may have to consider the impact altitude has on exercise-mediated hypoglycemia.

Oculometric Feature Changes During Acute Hypoxia in a Simulated High-Altitude Airdrop Scenario

BACKGROUND: Severe acute hypoxia results in a rapid deterioration of cognitive functioning and thus poses a risk for human operations in high altitude environments. This study aimed at investigating the effects of oxygen system failure during a high-altitude high-opening (HAHO) parachute jump scenario from 30,000 ft (9144 m) on human physiology and cognitive performance using a noncontact eye-tracking task.METHODS: Nine healthy male volunteers (ages 27–48) were recruited from the Norwegian Special Operations Commandos. Eye-tracking data were collected to derive information on cognitive performance in the context of rapid dynamic changes in pressure altitude while performing a modified King-Devick test. The baseline data was collected at 8000 ft (2438 m) while breathing 100% oxygen during decompression. For every test, the corresponding arterial blood gas analysis was performed.RESULTS: The study subjects endured severe hypoxia, which resulted in significant prolongations of fixation time (range: 284.1–245.6 ms) until 23,397 ft (131 m) and fixation size (range: 34.6–32.4 mm) until 25,389 ft (7739 m) as compared to the baseline (217.6 ± 17.8 ms and 27.2 ± 4.5 mm, respectively). The increase in the saccadic movement and decrease in the saccadic velocity was observed until 28,998 ft and 27,360 ft (8839 and 8339 m), respectively.DISCUSSION: This is the first study to investigate cognitive performance from measured oculometric variables during severe hypobaric hypoxia in a simulated high-altitude airdrop mission scenario. The measurement of altered oculometric variables under hypoxic conditions represents a potential avenue to study altered cognitive performance using noncontact sensors that can derive information and serve to provide the individual with a warning from impending incapacitation.Pradhan GN, Ottestad W, Meland A, Kåsin JI, Høiseth LØ, Cevette MJ, Stepanek J. Oculometric feature changes during acute hypoxia in a simulated high-altitude airdrop scenario. Aerosp Med Hum Perform. 2021; 92(12):928–936.

Pharmacokinetics of Acetaminophen and Metformin Hydrochloride in Rats After Exposure to Simulated High Altitude Hypoxia

The pharmacokinetic characteristics of drugs were altered under high altitude hypoxia, thereby affecting the absorption, distribution, metabolism, and excretion of drug. However, there are few literatures on the pharmacokinetic changes of antipyretic and pain-relieving drugs and cardiovascular system drugs at high altitude. This study aimed to evaluate the pharmacokinetics of acetaminophen and metformin hydrochloride in rats under simulated high altitude hypoxia condition. Mechanically, the protein and mRNA expression of uridine diphosphate glucuronyltransferase 1A1 (UGT1A1) and organic cation transporter 2 (OCT2) were investigated by enzyme linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. Compared with the normoxia group, the t1/2 and AUC of acetaminophen were significantly increased, and the CL/F was significantly decreased in rats after exposure to simulated high altitude hypoxia. The t1/2 of metformin hydrochloride was significantly increased by simulated high altitude hypoxia. No significant differences in AUC and CL/F of metformin hydrochloride were observed when comparing the hypoxia group with the normoxia group. The protein and mRNA expression of UGT1A1 and OCT2 were decreased significantly under hypoxia in rats. This study found obvious changes in the pharmacokinetics of acetaminophen and metformin hydrochloride in rats after exposure to simulated high altitude hypoxia, and they might be due to significant decreases in the expressions of UGT1A1 and OCT2. To sum up, our data suggested that the pharmacokinetics of acetaminophen and metformin hydrochloride should be reexamined, and the optimal dose should be reassessed under hypoxia exposure.

Splenic contraction is enhanced by exercise at simulated high altitude

Purpose Splenic contraction increases circulating hemoglobin (Hb) with advantages during hypoxia. As both hypoxia and exercise have been shown to be important separate triggers of splenic contraction we aimed to investigate if the spleen response to simulated high altitude (HA) is enhanced by superimposing exercise. Method Fourteen healthy volunteers (seven females) performed the following protocol in a normobaric environment sitting on an ergometer cycle: 20 min rest in normoxia; 20 min rest while breathing hypoxic gas simulating an altitude of 3500 m; 10 min exercise at an individually set intensity while breathing the hypoxic gas; 20 min rest in hypoxia; and finally 20 min rest in normoxia. Spleen measurements were collected by ultrasonic imaging and venous Hb measured at the end of each intervention. Result Mean ± SD baseline spleen volume during normoxic rest was 280 ± 107 mL, the volume was reduced by 22% during rest in hypoxia to 217 ± 92 mL (p < 0.001) and by 33% during exercise in hypoxia (189 mL; p < 0.001). Hb was 140.7 ± 7.0 g/L during normoxic rest and 141.3 ± 7.4 g/L during hypoxic rest (NS), but increased by 5.3% during hypoxic exercise (148.6 ± 6.3 g/L; p < 0.001). Spleen volume and Hb were stepwise changed back to baseline at cessation of exercise and return to normoxia. Conclusion Splenic contraction is induced by hypoxia and further enhanced by superimposing exercise, and reduced when exercise ceases, in a step-wise manner, showing that the tonic but partial contraction observed in long-term field expeditions to HA may occur also in the short term. This “graded response” may be beneficial during acclimatization to HA, to cope with moderate chronic hypoxia during rest while allowing additional enhancement of oxygen carrying capacity to overcome short bouts of extreme hypoxia caused by exercise.