Inhibition of 2-Oxoglutarate Dehydrogenase as a Chemical Model of Acute Hypobaric Hypoxia

Both hypoxia and inhibition of 2-oxoglutarate dehydrogenase complex (OGDHC) are known to change cellular amino acid pools, but the quantitative comparison of the metabolic and physiological outcomes has not been done. We hypothesize that OGDHC inhibition models metabolic changes caused by hypoxia, as both perturb the respiratory chain function, limiting either the NADH (OGDHC inhibition) or oxygen (hypoxia) supply. In the current study, we quantify the changes in the amino acid metabolism after OGDHC inhibition in the highly sensitive to hypoxia cerebellum and compare them to the earlier characterized changes after acute hypobaric hypoxia. In addition, the associated physiological effects are characterized and compared. A specific OGDHC inhibitor succinyl phosphonate (SP) is shown to act similar to hypoxia, increasing levels of many amino acids in the cerebellum of non-pregnant rats, without affecting those in the pregnant rats. Compared with hypoxia, stronger effects of SP in non-pregnant rats are observed on the levels of cerebellar amino acids, electrocardiography (ECG), and freezing time. In pregnant rats, hypoxia affects ECG and behavior more than SP, although none of the stressors significantly change the levels of cerebellar amino acids. The biochemical differences underlying the different physiological actions of SP and hypoxia are revealed by correlation analysis of the studied parameters. The negative correlations of cerebellar amino acids with OGDHC and/or tryptophan, shown to arise after the action of SP and hypoxia, discriminate the overall metabolic action of the stressors. More negative correlations are induced in the non-pregnant rats by hypoxia, and in the pregnant rats by SP. Thus, our findings indicate that the OGDHC inhibition mimics the action of acute hypobaric hypoxia on the cerebellar amino acid levels, but a better prediction of the physiological outcomes requires assessment of integral network changes, such as increases in the negative correlations among the amino acids, OGDHC, and/or tryptophan.

Experimental Brain Injury Induced by Acute Hypobaric Hypoxia Stimulates Changes in mRNA Expression and Stress Marker Status

The present study was proposed to investigate the brain injury under acute hypobaric hypoxia following alteration in mRNA expression and stress markers in a time-dependent manner. SD clean graded male rats were randomly divided into four groups for this experimental brain injury, the control group at Xining (altitude, 2270m) and hypoxia treatment groups with different time exposure day1, day2, and day3 at (altitude, 7000m) in a hypobaric chamber. After day3 exposure, the brain tissues were collected. The level of mRNA expression of VEGF and HIF1-α was assessed using qRT-PCR. The oxidative stress level of superoxide dismutase (SOD) and malondialdehyde (MDA) were determined with commercial kits. AHH with time duration significantly increased the MDA level and decreased in the activity of SOD was seen in all hypoxia treated groups as compared to the control (P< 0.001). The mRNA expression level of HIF1-α and VEGF in day1, day2, and day3 AHH groups was markedly raised when it is compared to control (P< 0.05). Ultimately, in conclusion, such results indicate that AHH stimulates oxidative stress induces brain damage in rats. Keywords: Acute hypobaric hypoxia, Brain injury, HIF-1α, Oxidative stress.

Antihypoxic activity of the VMA-10-18 derivate under hypobaric hypoxia in mice

The present study was carried out to evaluate the effect of a new derivative VMA-10-18 (10 mg/kg) on the resistance of mice to acute hypobaric hypoxia. It was confirmed that the studied derivative contributes to an increase in the life time on the lethal test site by 2,7 times (p <0,05) compared with the control group of animals and exceeds the strength of the effect of the reference drug Metaprot by 1,2 (p <0,05).

Theory of hibernament ensembles and the possibility of its use to ensure life activity for extremal impacts

The possibility of efficient use of the theory of hibernation ensembles to ensure vital activity in extreme conditions is considered. Hibernation ensembles are strictly selected sets of tools, among which are special combinations of pharmacological preparations and hypostabilizers, respiratory mixtures different in gas composition, controlled hypothermia, etc., which, when coordinated, cause the formation of a special state of the body, referred to as «hypobiosis and cryobiosis» or artificial hibernation. The data of experimental studies on changes in the body’s resistance to the extreme effects of gamma radiation, to acute hypobaric hypoxia and to flight overloads under conditions of artificially induced hibernation are generalized to determine the possibility of using the theory of hibernation ensembles while ensuring vital activity under extreme influences. It is shown that under the influence of vegetotropic agents against the background of hypothermia, the metabolic processes slow down significantly and the organism of warm-blooded animals begins to acquire ambient temperature. The condition that occurs in this case is accompanied by an increase in the body’s resistance to extreme factors, such as acute hypobaric hypoxia, deep hypothermia, exposure to ionizing radiation, toxic lesions, massive blood loss, pain shock, etc. This area of research is of particular relevance for the development of methods for long-term life support person in extreme conditions, with severe injuries and in the provision of medical care in conditions of mass admission victims, since it provides a reserve of time necessary for organizing the safe transportation of victims to the places of specialized and high-tech medical care, that is, actually providing medical care at a later date.

Concurrent white noise and acute hypobaric hypoxia: Effect on aviation cognitive performance

Introduction: Optimal cognitive performance is the essence of effective execution of a flying mission. Effects of two commonly encountered aviation stressors, hypoxia and noise, on performance have been studied. However, studies on effects of concurrent dual effects of both these stressors on key cognitive parameters are sparse; hence, the objective was to examine these effects. Material and Methods: Cognitive performances were assessed among 30 healthy volunteers (28 males and 2 females) sequentially in four different conditions – baseline (without stressors), 85 dB(A) noise, 14,000 ft altitude, and concurrent exposure to 85 dB(A) noise at 14,000 ft altitude. White noise was simulated through software, altitude in the hypobaric chamber and cognitive performance was assessed with tests from Psychology Experiment Building Language (PEBL) test battery. Data were analyzed using descriptive statistics and repeated measures ANOVA. Results: The study revealed statistically significant direct detrimental effect of altitude and noise on implicit reaction time independently as well as concurrently. However, there was insignificant interaction effect between the dual stressors on implicit reaction time. There were no statistically significant effects of dual stressors on implicit correctness, visuospatial working memory, and selective attention. Although statistically not significant, noise enhanced the performance level in the form of increased Corsi block memory span and Corsi block total score. Conclusion: No significant effect of the dual stressors was observed on most of the cognitive parameters. However, implicit reaction time, a measure of pilot’s risk-taking behavior, was found to be significantly affected by the dual stressors. Further research with a larger sample of aircrew population who differ in age, experience, and other potentially influencing factors is recommended.