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.

Stress-induced antinociception to noxious heat requires α1A-adrenaline receptors of spinal inhibitory neurons in mice

It is well known that acute exposure to physical stress produces a transient antinociceptive effect (called stress-induced analgesia [SIA]). One proposed mechanism for SIA involves noradrenaline (NA) in the central nervous system. NA has been reported to activate inhibitory neurons in the spinal dorsal horn (SDH), but its in vivo role in SIA remains unknown. In this study, we found that an antinociceptive effect on noxious heat after acute exposure to restraint stress was impaired in mice with a conditional knockout of α1A-adrenaline receptors (α1A-ARs) in inhibitory neurons (Vgat-Cre;Adra1aflox/flox mice). A similar reduction was also observed in mice treated with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine, a selective neurotoxin for NAergic neurons in the locus coeruleus (LC). Furthermore, whole-cell patch-clamp recordings using spinal cord slices revealed that NA-induced increase in the frequency of spontaneous inhibitory postsynaptic currents in the substantia gelatinosa neurons was suppressed by silodosin, an α1A-AR antagonist, and by conditional knockout of α1A-ARs in inhibitory neurons. Moreover, under unstressed conditions, the antinociceptive effects of intrathecal NA and phenylephrine on noxious heat were lost in Vgat-Cre;Adra1aflox/flox mice. Our findings suggest that activation of α1A-ARs in SDH inhibitory neurons, presumably via LC-NAergic neurons, is necessary for SIA to noxious heat.

Dissimilar Anxiety-like Behavior in Prepubertal and Young Adult Female Rats on Acute Exposure to Aluminium

Background: Puberty is a developmental transition in which an estrogenic surge occurs, mediating the release of xenoestrogens, like aluminium. Aluminium’s effect on anxiety in rodents at the different developmental stages is inconsistent. Aims: This study aimed at investigating the effect of the metalloestrogenic property of aluminium on anxiety-like behavioral changes in prepubertal and young adult female rats. Objective: Considering this aim, our objective was to evaluate the anxiety-like behavior by the elevated plus maze in prepubertal and young adult female rats with or without acute exposure to aluminium. Methods: To address this property of aluminium, 5mg/Kg body weight (Al-5) and 10 mg/Kg body weight (Al-10) of aluminium was administered intraperitoneally to female rats at two developmental stages, prepubertal (PP; n = 8 for each dose) and young adult (YA; n = 6 for each dose) for two weeks. Post-treatment, three days behavioral assessment of the rats was done employing elevated plus maze. Results: Reduced escape latency was seen in Al-5, Al-10 pre-pubertal rats, and Al-5 young-adult rats on day 3. A significant reduction in open arm time was seen in the Al-5 young-adult rats. Aluminium treatment in the pre-pubertal rats reduced their head dipping and grooming. Reduced sniffing, head dipping, and stretch-attended posture in the treated young-adult female rats showed that they had impaired risk-taking tendency. Conclusion: Differential effect on the anxiety-like behavior in the pre-pubertal and young-adult female rats might be due to the metalloestrogenic property of aluminium, acting differently on the two age groups.

Effect of Acute Exposure to Altitude on the Quality of Chest Compression‐Only Cardiopulmonary Resuscitation in Helicopter Emergency Medical Services Personnel: A Randomized, Controlled, Single‐Blind Crossover Trial

Background Helicopter emergency medical services personnel operating in mountainous terrain are frequently exposed to rapid ascents and provide cardiopulmonary resuscitation (CPR) in the field. The aim of the present trial was to investigate the quality of chest compression only (CCO)‐CPR after acute exposure to altitude under repeatable and standardized conditions. Methods and Results Forty‐eight helicopter emergency medical services personnel were divided into 12 groups of 4 participants; each group was assigned to perform 5 minutes of CCO‐CPR on manikins at 2 of 3 altitudes in a randomized controlled single‐blind crossover design (200, 3000, and 5000 m) in a hypobaric chamber. Physiological parameters were continuously monitored; participants rated their performance and effort on visual analog scales. Generalized estimating equations were performed for variables of CPR quality (depth, rate, recoil, and effective chest compressions) and effects of time, altitude, carryover, altitude sequence, sex, qualification, weight, preacclimatization, and interactions were analyzed. Our trial showed a time‐dependent decrease in chest compression depth ( P =0.036) after 20 minutes at altitude; chest compression depth was below the recommended minimum of 50 mm after 60 to 90 seconds (49 [95% CI, 46–52] mm) of CCO‐CPR. Conclusions This trial showed a time‐dependent decrease in CCO‐CPR quality provided by helicopter emergency medical services personnel during acute exposure to altitude, which was not perceived by the providers. Our findings suggest a reevaluation of the CPR guidelines for providers practicing at altitudes of 3000 m and higher. Mechanical CPR devices could be of help in overcoming CCO‐CPR quality decrease in helicopter emergency medical services missions. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04138446.