Effects Of Acute Hypobaric Hypoxia Research Articles

Potential therapeutic effects of traditional Chinese medicine in acute mountain sickness: pathogenesis, mechanisms and future directions.

Acute mountain sickness (AMS) is a pathology with different symptoms in which the organism is not adapted to the environment that occurs under the special environment of high altitude. Its main mechanism is the organism's tissue damage caused by acute hypobaric hypoxia. Traditional Chinese medicine (TCM) theory focuses on the holistic concept. TCM has made remarkable achievements in the treatment of many mountain sicknesses. This review outlines the pathogenesis of AMS in modern and traditional medicine, the progress of animal models of AMS, and summarizes the therapeutic effects of TCM on AMS. Using the keywords "traditional Chinese medicine," "herbal medicine," "acute mountain sickness," "high-altitude pulmonary edema," "high-altitude cerebral edema," "acute hypobaric hypoxia," and "high-altitude," all relevant TCM literature published up to November 2023 were collected from Scopus, Web of Science, PubMed, and China National Knowledge Infrastructure databases, and the key information was analyzed. We systematically summarised the effects of acute hypobaric hypoxia on the tissues of the organism, the study of the methodology for the establishment of an animal model of AMS, and retrieved 18 proprietary Chinese medicines for the clinical treatment of AMS. The therapeutic principle of medicines is mainly invigorating qi, activating blood and removing stasis. The components of botanical drugs mainly include salidroside, ginsenoside Rg1, and tetrahydrocurcumin. The mechanism of action of TCM in the treatment of AMS is mainly through the regulation of HIF-1α/NF-κB signaling pathway, inhibition of inflammatory response and oxidative stress, and enhancement of energy metabolism. The main pathogenesis of AMS is unclear. Still, TCM formulas and components have been used to treat AMS through multifaceted interventions, such as compound danshen drip pills, Huangqi Baihe granules, salidroside, and ginsenoside Rg1. These components generally exert anti-AMS pharmacological effects by inhibiting the expression of VEGF, concentration of MDA and pro-inflammatory factors, down-regulating NF-κB/NLRP3 pathway, and promoting SOD and Na + -K + -ATPase activities, which attenuates acute hypobaric hypoxia-induced tissue injury. This review comprehensively analyses the application of TCM in AMS and makes suggestions for more in-depth studies in the future, aiming to provide some ideas and insights for subsequent studies.

Transcriptomic analysis of the cerebral hippocampal tissue in spontaneously hypertensive rats exposed to acute hypobaric hypoxia: associations with inflammation and energy metabolism

We evaluated the effect of acute hypobaric hypoxia (AHH) on the hippocampal region of the brain in early-stage spontaneously hypertensive male rats. The rats were classified into a control (ground level; ~ 400 m altitude) group and an AHH experimental group placed in an animal hypobaric chamber at a simulated altitude of 5500 m for 24 h. RNA-Seq analysis of the brains and hippocampi showed that differentially expressed genes (DEGs) were primarily associated with ossification, fibrillar collagen trimer, and platelet-derived growth factor binding. The DEGs were classified into functional categories including general function prediction, translation, ribosomal structure and biogenesis, replication, recombination, and repair. Pathway enrichment analysis revealed that the DEGs were primarily associated with relaxin signaling, PI3K-Akt signaling, and amoebiasis pathways. Protein–protein interaction network analysis indicated that 48 DEGs were involved in both inflammation and energy metabolism. Further, we performed validation experiments to show that nine DEGs were closely associated with inflammation and energy metabolism, of which two (Vegfa and Angpt2) and seven (Acta2, Nfkbia, Col1a1, Edn1, Itga1, Ngfr, and Sgk1) genes showed up and downregulated expression, respectively. Collectively, these results indicated that inflammation and energy metabolism-associated gene expression in the hippocampus was altered in early-stage hypertension upon AHH exposure.

Differences in mitochondrial function between brain and heart of senile rats exposed to acute hypobaric hypoxia. Role of nitric oxide

Rat brain and heart display different endogenous protective responses against hypobaric hypoxia in an age-dependent way. The aim of the present work was to evaluate the effects of acute hypobaric hypoxia (HH, 48 h) on brain and heart mitochondrial function as well as the participation of nitric oxide (NO) in old rats (22-month old).Cortical mitochondria from rats exposed to HH decreased respiratory rates (37 %, state 3) and membrane potential (20 %), but NO and H2O2 production increased by 48 %, and 23 %, respectively. Hippocampal mitochondria preserved O2 consumption and H2O2 production, decreased membrane potential (18 %) and increased NO production (46 %). By contrast, HH decreased NO production (53 %) in mitochondria from left heart ventricles associated with increased cytochrome oxidase activity (39 %) and decreased NADPH oxidase activity (31 %). Also, a tendency to increase complex I-III (24 %) and complex II-III (65 %) activity was observed.In conclusion, after HH hippocampal and cortical mitochondria showed mild uncoupling and increased NO production. However, only the hippocampus preserved O2 consumption and H2O2 levels. Interestingly, heart mitochondria showed a decreased ROS production through increased cytochrome oxidase activity associated with a decrease in NO production. This may be interpreted as a self-protective mechanism against hypoxia.

Acute Hypobaric Hypoxia Exposure Causes Neurobehavioral Impairments in Rats: Role of Brain Catecholamines and Tetrahydrobiopterin Alterations.

Hypoxia is a state in which the body or a specific part of the body is deprived of adequate oxygen supply at the tissue level. Sojourners involved in different activities at high altitudes (> 2500m) face hypobaric hypoxia (HH) due to low oxygen in the atmosphere. HH is an example of generalized hypoxia, where the homeostasis of the entire body of an organism is affected and results in neurochemical changes. It is known that lower O2 levels affect catecholamines (CA), severely impairing cognitive and locomotor behavior. However, there is less evidence on the effect of HH-mediated alteration in brain Tetrahydrobiopterin(BH4) levels and its role in neurobehavioral impairments. Hence, this study aimed to shed light on the effect of acute HH on CA and BH4 levels with its neurobehavioral impact on Wistar rat models. After HH exposure, significant alteration of the CA levels in the discrete brain regions, viz., frontal cortex, hippocampus, midbrain, and cerebellum was observed. HH exposure significantly reduced spontaneous motor activity, motor coordination, and spatial memory. The present study suggests that the HH-induced behavioral changes might be related to the alteration of the expression pattern of CA and BH4-related genes and proteins in different rat brain regions. Overall, this study provides novel insights into the role of BH4 and CA in HH-induced neurobehavioral impairments.

Dynamic Range of Luminance Perception in Acute Hypobaric Hypoxia.

Rizzi, Alessandro, Alice Plutino, Diego Vecchi, Anton Giulio Guadagno, and Marco Lucertini. Dynamic range of luminance perception in acute hypobaric hypoxia. High Alt Med Biol. 23:313-318, 2022.-The effects of acute hypobaric hypoxia, as potentially experienced in high altitude flight, on the detection of low contrast targets within a high dynamic range (DR) of luminance were investigated. The tests were performed after 10 minutes of adaptation to an ambient luminance level of 0.2 lx. Twenty-four individuals were exposed to hypobaric hypoxia at an altitude of 18,000 ft (5,490 m) inside a hypobaric chamber and were asked to identify the darkest one perceived from a grid of progressively less luminous patches. The results were compared with those obtained by the same subjects at sea level. The results indicate a global reduction of the DR perception during hypoxia, with a mean decrease of 0.023 cd/m2 (standard deviation ±0.064), which resulted statistically significant (p < 0.05). No significant correlations with oxygen saturation levels were observed. These findings might have practical applications in the design of cockpit's instruments, especially those dedicated to night-time flight missions at high altitudes.

Acute Hypobaric and Hypoxic Preconditioning Reduces Myocardial Ischemia-Reperfusion Injury in Rats.

Background Chronic and/or intermittent exposure to hypobaric hypoxia reportedly exerts cardioprotective effects against ischemia-reperfusion injury. However, few studies have focused on the cardioprotective effects of acute and/or short-term hypobaric and hypoxic exposures. This study investigated the effects of acute hypobaric hypoxia on myocardial ischemia-reperfusion injury. Materials and Methods Rats were assigned to groups receiving normobaric normoxia (NN group), hypobaric hypoxia (HH group), or normobaric hypoxia (NH group). HH group rats were exposed to 60.8 kPa and 12.6% fraction of inspired oxygen in a hypobaric chamber for 6 h. NH group rats were exposed to hypoxic conditions under normal pressure. After each exposure, 30 min of myocardial ischemia was followed by 60 min of reperfusion. Cardiac function and infarct size were determined after reperfusion. Expression of hypoxia-inducible factor 1 alpha (HIF1α) was also measured. Results Cardiac function was better preserved in the HH and NH groups than in the NN group (p < 0.01 each). Median infarct size/area at risk was significantly lower in the HH group (50%, interquartile range [IQR] 48–54%; p < 0.01 vs. NN group) and NH group (45%, IQR 36–50%; p < 0.01 vs. NN group) than in the NN group (72%, IQR 69–75%). HIF1α expression was significantly higher in the HH group (p < 0.05 vs. NN group) and NH group (p < 0.01 vs. NN group) than in the NN group. Conclusions Exposure to acute and/or short-term hypobaric and hypoxic conditions might exert cardioprotective effects against myocardial ischemia-reperfusion injury via HIF1α modulation.

Role of TLR4/NF-κB pathway in the damage of acute hypobaric hypoxia to small intestinal mucosa in rats.

The purpose of this study was to investigate the effect of acute hypobaric hypoxia (HH) exposure on small intestinal mucosa in rats and its underling mechanism. The pathological changes of rat small intestine mucosa were detected by HE staining. The expressions of TLR4 and NF-κB in the small intestine were detected by immunohistochemistry (IHC). The levels of Zonulin, TNF-α, IL-1β, and IL-6 in the serum were detected by ELISA. The proportion of natural killer (NK) cells and dendritic cell population in the small intestine was analyzed by flow cytometry. The mRNA and protein levels of TLR4, NF-κB, occludin, HIF-1α, and iNOS were detected by RT-qPCR and Western blot, respectively. Compared with the Control group, the HH groups had different degrees of injury in intestinal mucosa. Meanwhile, in the HH groups, it was also found the increased levels of Zonulin, TNF-α, IL-1β and IL-6 in the serum, the increased CD4+/CD8+T cells ratio and small intestine NK cells population, the increased mRNA and protein expression levels of small intestine TLR4, NF-κB, HIF-1α and iNOS, and the decreased mRNA and protein expression levels of occludin. Acute HH may damage the intestinal mucosa of rats by inducing TLR4/NF-κB pathway overexpression.

Cardioprotection after acute exposure to simulated high altitude in rats. Role of nitric oxide

AimIn previous studies, upregulation of NOS during acclimatization of rats to sustained hypobaric hypoxia was associated to cardioprotection, evaluated as an increased tolerance of myocardium to hypoxia/reoxygenation. The objective of the present work was to investigate the effect of acute hypobaric hypoxia and the role of endogenous NO concerning cardiac tolerance to hypoxia/reoxygenation under β-adrenergic stimulation. MethodsRats were submitted to 58.7 kPa in a hypopressure chamber for 48 h whereas their normoxic controls remained at 101.3 kPa. By adding NOS substrate L-arg, or blocker L-NNA, isometric mechanical activity of papillary muscles isolated from left ventricle was evaluated at maximal or minimal production of NO, respectively, under β-adrenergic stimulation by isoproterenol, followed by 60/30 min of hypoxia/reoxygenation. Activities of NOS and cytochrome oxidase were evaluated by spectrophotometric methods and expression of HIF1-α and NOS isoforms by western blot. Eosin and hematoxiline staining were used for histological studies. ResultsCytosolic expression of HIF1-α, nNOS and eNOS, and NO production were higher in left ventricle of hypoxic rats. Mitochondrial cytochrome oxidase activity was decreased by hypobaric hypoxia and this effect was reversed by L-NNA. After H/R, recovery of developed tension in papillary muscles from normoxic rats was 51–60% (regardless NO modulation) while in hypobaric hypoxia was 70% ± 3 (L-arg) and 54% ± 1 (L-NNA). Other mechanical parameters showed similar results. Preserved histological architecture was observed only in L-arg papillary muscles of hypoxic rats. ConclusionExposure of rats to hypobaric hypoxia for only 2 days increased NO synthesis leading to cardioprotection.

Dissociated Components of Executive Control in Acute Hypobaric Hypoxia.

The neurocognitive effects of acute hypobaric hypoxia are still largely unknown. This study was designed to test the hypothesis that executive control, an important component of cognition, is especially vulnerable to hypoxia. Subjects participated in a simulated hypobaric chamber flight to 5500 m. Four auditory tasks were presented before, during, and after hypoxia: 1) Voice, and 2) Name variant of the Stroop task (both measuring conflict resolution); 3) go/no-go task (GNG; measuring inhibition); and 4) two-choice reaction time task (CRT; which is a noninhibitory control task). The Stroop effect increased during hypoxia: in the Voice Stroop it increased from 49.4 to 83.6 ms for reaction time and from 4.1 to 12.3% for accuracy; in the Name Stroop from 43.5 to 82.9 ms for reaction time (accuracy remained unchanged). Accuracy declined from 82.3 to 75.0% in CRT, and from 85.8 to 77.5% (averaged over stimulus types) in the GNG task. Importantly, accuracy decreased similarly to go and no-go stimuli in the GNG task, revealing unaffected inhibition. The findings suggest that tasks requiring conflict resolution are more likely to be impaired than tasks requiring inhibition of response. Furthermore, our results provide evidence for the distinct nature of inhibitory control functions.Takács E, Czigler I, Pató LG, Balázs L. Dissociated components of executive control in acute hypobaric hypoxia. Aerosp Med Hu Perform. 2017; 88(12):1081-1087.

The Effect of Acute Simulated Altitude on the Lactate Thresholds of Well-Trained Cyclists

PURPOSE: Endurance cyclists often race or train at altitudes ranging from 1,000-3,000 m above sea level. It is well known that peak oxygen consumption (VO2peak) and mean power output (PO) decrease with increasing altitude. However, factors such as lactate thresholds are also important for endurance performance. Research investigating the response of the lactate thresholds to acute hypoxia is however scarce. The aim of this study was to quantify and titrate the acute effect of simulated altitude on the lactate thresholds of well-trained cyclists. METHODS: Ten well-trained, non-altitude acclimatized male cyclists and triathletes completed a graded cycling exercise test in a hypobaric chamber at each of four simulated altitudes (200, 1,200, 2,200, 3,200 m). The test protocol comprised 5 x 5-min submaximal efforts (50, 100, 150, 200 and 250 W), to determine VO2, heart rate (HR) and blood lactate concentration ([La-]) responses. Following a 10 min passive rest, a 5-min maximal time-trial (5-minTT) was performed to determine peak physiological and performance responses. Combining these measures allowed a modified 2-in-1 protocol to be applied to calculate the lactate thresholds (LT1, LT2) using customized software (ADAPT). RESULTS: VO2 decreased by 5.5 ± 1.1%, 15.9 ± 1.5% and 26.3 ± 1.4% at LT1 and by 6.5 ± 1.2%, 13.4 ± 1.3% and 23.2 ± 1.8% at LT2 at 1,200, 2,200 and 3,200 m compared with 200 m respectively, P<0.05. Mean PO declined by 5.4 ± 1.1%, 17.7 ± 1.7% and 30.3 ± 1.9% for LT1 and by 5.2 ± 1.3%, 13.9 ± 1.4% and 25.7 ± 1.8% at LT2 at 1,200, 2,200 and 3,200 m compared with 200 m respectively, P<0.05. HR and [La-] at these thresholds remained unchanged. 5-minTT VO2peak and PO both followed the same pattern of decline with increasing altitude, P<0.05. CONCLUSIONS: A dose response effect of acute hypobaric hypoxia on VO2 and PO was found at both submaximal (LT1 and LT2) and maximal (5-minTT) intensities. No such effects were seen for HR or [La-] at any intensity.

Oxidative Stress in Acute Hypobaric Hypoxia.

Irarrázaval, Sebastián, Claudio Allard, Juan Campodónico, Druso Pérez, Pablo Strobel, Luis Vásquez, Inés Urquiaga, Guadalupe Echeverría, and Federico Leighton. Oxidative stress in acute hypobaric hypoxia. High Alt Med Biol. 18:128-134, 2017.-The effects of acute hypobaric hypoxia endured by mountaineers were studied, specifically as evidenced by acute mountain sickness (AMS) and oxidative stress damage. Ten male volunteers were exposed to acute hypobaric hypoxia, and AMS was evaluated through arterial oxygen saturation (SaO2), cardiac rate, and the Lake Louise Score (LLS). Oxidative stress was determined through blood profile tests performed 24 hours before and after high-altitude exposure, assessing the oxidative damage and antioxidant profiles. Dietary habits were assessed using the Chilean Mediterranean Diet Index. During ascent (i.e., first 8 hours), all volunteers presented AMS (LLS ≥3 points), as manifested by a median LLS increment of four points, a 15 bpm cardiac rate, and 17% decrease in SaO2. Additionally, plasma lipid oxidative damage increased after the expedition, as evaluated through malondialdehyde, which was directly correlated with the LLS (R2 = 0.720, p = 0.003) and inversely correlated with SaO2 (R2 = 0.436; p = 0.035) at a high altitude. Preascent carbonyl levels were inversely correlated to SaO2 (R2 = 0.490; p = 0.008) and directly correlated to cardiac rate (R2 = 0.225, p = 0.016) at a high altitude. Moreover, dietary habits were inversely correlated with increased carbonyls during the expedition (R2 = 0.436; p = 0.047). In conclusion, acute hypobaric hypoxia induced AMS and an increment in oxidative stress markers 24 hours after altitude exposure in the volunteers. Furthermore, oxidative stress damage was related to AMS severity. Finally, volunteers with closer adherence to a Mediterranean diet presented a lower increase in oxidative damage during ascent, reflecting the potential preventive role of diet against AMS.

Effects of rapid ascent on the heart rate variability of individuals with and without acute mountain sickness.

Through time- and frequency-domain analysis, we compared the effects of acute hypobaric hypoxia on the changes in heart rate variability (HRV) following night sleeping and morning awakening in individuals with and without acute mountain sickness (AMS). Thirty-nine nonacclimatised healthy individuals were transported by bus from sea level to 3150m within 3h. Short-term HRV was measured two times a day-before sleeping (BS) and after awakening (AA)- at 3 days before ascent (T0), two consecutive nights at 3150m (T1 and T2), and 2 days after descent (T3). AMS was diagnosed using the self-reported Lake Louise score questionnaire. AMS developed in 19 of 39 participants (48.7%). At sea level, individuals had higher HRV at AA than at BS, and the trend of increased HRV at AA remained unchanged at high altitude, irrespective of AMS. At T1 BS, low-frequency power in normalised unit was significantly lower in participants with AMS than in those without AMS. Compared with those at T1 BS, the square root of the mean squared differences of successive normal-normal (NN) intervals, the number of interval differences of successive NN intervals more than 50ms (NN50), and the proportion derived by dividing NN50 by the total number of NN intervals at T1 AA significantly increased in participants without AMS but nonsignificantly decreased in those with AMS. After rapid ascent, individuals with AMS did not demonstrate sympathetic hyperactivity but did exhibit withdrawal of cardiac vagal modulation in the morning following the first night's sleep.

Vascular reactivity and biomarkers of endothelial function in healthy subjects exposed to acute hypobaric hypoxia

AimsThe aim of this study was to evaluate the effects of acute hypobaric hypoxia (HH) on vascular reactivity and biochemical markers associated with endothelial function (EF). Main methodsTen healthy subjects were exposed to a simulated altitude of 4,000meters above sea level for 4hours in a hypobaric chamber. Vascular reactivity was measured by the flow-mediated vasodilatation (FMVD) test. Endothelin-1, high sensitive-C reactive protein (hsCRP), vascular cell adhesion molecule 1, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), paraoxonase and adiponectin levels, and FMVD were evaluated before and after the exposure. Key findingsSubjects were young (age: 32±6years), lean [body mass index: 23.9±2.0kg/m2, waist circumference: 77(IQR: 72–80) cm], and presented normal clinical and biochemical parameters. No significant changes were evidenced in FMVD in response to HH (pre: 0.45 (0.20–0.70) vs. during: 0.50 (0.20–1.22) mm; p=0.594). On the other hand, endothelin-1 (+54%, p<0.05), hsCRP (+37%, p<0.001), IL-6 (+75%, p<0.05), TNF-α (+75%, p<0.05), and adiponectin (−39%, p<0.01) levels were significantly altered post-HH. FMVD was increased in 7 subjects, and it was decreased in 3 individuals during HH exposure. Interestingly, when EF biomarkers were compared between these two subgroups of subjects, only post exposure-adiponectin levels were significantly different (49±5 vs. 38±6μg/ml, respectively, p<0.05). SignificanceHH exposure had an effect on endothelin-1, adiponectin, hsCRP, IL-6, and TNF-α concentration. However, adiponectin was the only biomarker associated with an altered vascular reactivity.

Effect of acute hypobaric hypoxia on the endothelial glycocalyx and digital reactive hyperemia in humans

Introduction: Hypoxia is associated with increased capillary permeability. This study tested whether acute hypobaric hypoxia involves degradation of the endothelial glycocalyx.Methods: We exposed 12 subjects to acute hypobaric hypoxia (equivalent to 4500 m for 2–4 h) and measured venous blood concentrations of biomarkers reflecting endothelial and glycocalyx degradation (catecholamines, syndecan-1, soluble CD40 ligand, protein C, soluble thrombomodulin, tissue-type plasminogen activators, histone-complexed DNA fragments, and nitrite/nitrate). Endothelial function was assessed by the hyperemic response to brachial artery occlusion by peripheral arterial tonometry.Results: Compared with normoxic baseline levels, hypoxia increased concentrations of syndecan-1 from 22 (95% confidence interval: 17–27) to 25 (19–30) ng/ml (p < 0.02) and protein C from 76 (70–83)% to 81 (74–88)% (p < 0.02). Nitrite/nitrate decreased from 23 (18–27) μM at baseline to 19 (14–24) μM and 18 (14–21) μM in hypoxia and recovery, respectively (p < 0.05). Other biomarkers remained unchanged. The post-occlusion/pre-occlusion ratio (reactive hyperemia index, RHI) decreased from 1.80 (1.52–2.07) in normoxia to 1.62 (1.28–1.96) after 2–4 h of hypobaric hypoxia and thereafter increased to 2.43 (1.99–2.86) during normoxic recovery (p < 0.01).Conclusions: The increase in syndecan-1 and protein C suggests that acute hypobaric hypoxia produces a minor degree of glycocalyx degradation and overall cellular damage. After hypoxia RHI rebounded to higher than baseline levels suggesting improved endothelial functionality.

Effects of acute hypobaric hypoxia on abilities of learning and memory, the level of nitric oxide and endothelin-1 in hippocampus of mice

Objective To examine the effects of acute hypobaric hypoxia on abilities of learning and memory, the water content in brain, the level of nitric oxide(NO) and endothelin-1(ET-1) in hippocampus of mice. Methods The acute hypobaric hypoxia environment were made by putting the mice in a hypobaric chamber simulated at altitude of 6 000 meters for 8 hours.The capabilities of learning and memory of mice were detected by Morris water maze test.The content of water in hippocampus were examined by measuring the ratio of dry/wet weight, and the level of NO and ET-1 in brain was detected by colorimetric method. Results Morris water maze test showed that the mean escape latency of mice in the hypobaric hypoxia group were longer than that in the normobaric normoxia group((44.60±7.80)s vs (26.39±8.44)s, P<0.01), and the target quadrant residence time were decreased((19.78±2.74)s vs (22.98±6.14)s, P<0.05). Compared with the normobaric normoxia group(NO: (2.37±1.07)μmol/gProt, ET-1: (38.87±6.17)ng/L), the water content in brain of mice in the hypobaric hypoxia group was increased(P<0.05), meanwhile, both the level of NO((4.48±1.45)μmol/gProt) and ET-1((52.09±6.75)ng/L) in brain were increased too(P<0.01). Conclusion Hypobaric hypoxia can decrease the abilities of learning and memory of mice, and these changes might be related with the increased water content and the increased level of NO and ET-1 in hippocampus of mice. Key words: Hypobaric hypoxia; Learning and memory; Nitric oxide; Endothelin-1

Transgenerational Sequelae of Acute Antenatal Stress in Pregnant Rats

We report here the first studies of the effects of acute hypobaric hypoxia (AHH)during the period of early organogenesis on three sequential generations: the generation including pregnant females exposed to AHH (F0) and the two subsequent generations – F1 and F2. All three generations showed significant abnormalities in behavioral measures of motor and orientational-investigative activity, reflecting the state of anxiety, while generations F1 and F2 also showed changes in the ability of offspring to learn with positive reinforcement. These changes persisted to the pubertal period of life. In addition, females of generations F0 and F1 showed influences of AHH on maternal behavior, these influences being in different directions. The possible mechanisms of the effects of gestational stress during early organogenesis on subsequent generations are discussed.

Working Memory Impairment in Pilots Exposed to Acute Hypobaric Hypoxia

During an acute hypoxia exposure, impairment of memory is one of the most frequently reported symptoms, either during hypoxia awareness training of aircrews or after an in-flight hypoxic incident. However, the effects of acute hypoxia on memory have been little studied in laboratory-controlled conditions. Moreover, none of these studies were performed in hypobaric conditions. The main aim of our study was to investigate the effects of acute hypobaric hypoxia on working memory (WM). This study also aimed to find links between physiological measurements and cognitive performance during acute hypoxia exposure. During hypoxia awareness training, 28 subjects (experimental group) were exposed to a simulated altitude level of 10,000 m (31,000 ft) in a hypobaric chamber, while 29 subjects (control group) stayed at sea level. WM was assessed in both groups with the Paced Auditory Serial Addition Test (PASAT). Peripheral oxygen saturation (SpO2) and heart rate were recorded. WM was strongly impaired in the hypoxic group. One major finding is that hypoxia highly increased the mean error frequency rate. WM performance decreased linearly with hypoxemia, but SpO2 was weakly predictive of PASAT performance and vice versa. WM is impaired by acute hypobaric hypoxia. Given the importance of WM in aircraft piloting and its sensitivity to hypoxia, the PASAT, in association with SpO2 and EEG recordings, could improve both hypoxia training and our understanding of the effects of hypoxia on memory.

Hepatic metabolism of ibuprofen in rats under acute hypobaric hypoxia

Hypobaric hypoxia induced at high altitude causes a subnormal oxygen concentration in cells which affects the drug metabolic and pharmacokinetic (PK) capacity of the body. The metabolism and PK of drugs like ibuprofen may be impaired under hypoxia and may require a different than usual therapeutic dose regimen to ensure safe therapy. The present investigation was undertaken to evaluate the effect of acute hypobaric hypoxia (AHH) on hepatic metabolism and PK of ibuprofen in rats. Animals were exposed to simulated altitude of 7620 m (∼25,000 ft) for AHH exposure (6 and 24 h) in a decompression chamber and were administrated with single dose of ibuprofen (80 mg/kg body weight, p.o.). The results showed that GST activity was significantly reduced at 6 h (15%) and 24 h (23%) (p<0.05) in hypoxic group as compared to normoxic. A significant increase by 20-24% (p<0.05) in AST level was observed after AHH exposure. LDH activity also exhibited significant increase (p<0.05) after 24h of AHH. A significant down-regulated CYP2C9 level and mild histopathological changes were observed after 24h of AHH. Furthermore, PK variables viz. elimination half-life (T½) and mean residence time (MRT) of ibuprofen exhibited significant increase by 42% and 51% (p<0.05) respectively after 24h of AHH. Thus, results suggest that AHH exposure of 24h significantly affects phase II conjugation pathway, CYP2C9 level, AST level, liver histology and PK parameters. This asserts that AHH can impair disposition of ibuprofen however, it requires further investigation under chronic hypobaric hypoxic conditions.

The Effects of Acute Hypobaric Hypoxia on Arterial Stiffness and Endothelial Function and its Relationship to Changes in Pulmonary Artery Pressure and Left Ventricular Diastolic Function

This study investigated, for the first time, the effects of simulated high altitude, following acute hypobaric hypoxia (HH), on simultaneous assessment of large artery stiffness and endothelial function and its inter-relationship to left ventricular (LV) diastolic function, pulmonary artery systolic pressure (PASP), and estimated PA vascular resistance (PVR). Ten healthy subjects were studied at baseline pre and following acute HH to 4800 m for a total of 180 minutes. Assessments of LV diastolic function, mitral inflow, estimated LV filling pressure (E/e'), PVR, and PASP were undertaken using transthoracic echocardiography. Simultaneous assessments of arterial stiffness index (SI), systemic vascular resistance (SVR), vascular tone, and endothelial function (reflective index [RI]) were performed using pulse contour analysis of the digital arterial waveform. Acute hypoxia led to a fall in SpO₂ (98.1±0.7 vs. 71.8±7.1%; p=0.0002), SVR (1589.1±191.2 vs. 1187.8±248.7; p=0.004), and RI (50.8±10.3 vs. 33.0±6.5%; p=0.0008) with an increase in PASP (24.3±2.2 to 35.0±5.3 mmHg; p=0.0001) and estimated PVR (116.40±19.0 vs. 144.6±21.5; p<0.001). There was no rise in either SI (p=0.13), mitral early annular early e' filling velocity or E/e'. There was a significant inverse correlation between SpO₂ and PASP (r=-0.77; p<0.0001), PVR (r=-0.57; p=0.008) and between the fall in SpO₂ and change (Δ) in RI (baseline vs. 150 min, r=-0.52; p<0.001). There was a modest inverse correlation between ΔRI (lower ΔRI=worsening endothelial function) and ΔPAP (r=-0.55; p=0.10) and a strong inverse correlation between ΔRI and ΔPVR (r=-0.89; p=0.0007). Acute hypobaric hypoxia does not significantly alter large artery stiffness or cause overt LV diastolic function. However, the degree of hypoxia influences both the systemic endothelial and pulmonary vascular responses. This noted association is intriguing and requires further investigation.

Transgeneration Effects of Antenatal Acute Hypoxia during Early Organogenesis

We studied the effect of acute hypobaric hypoxia in early organogenesis on physiological and behavioral parameters of second-generation albino rats. Antenatal acute hypoxia was followed by physical and sexual retardation, increase in the mortality rate, and behavioral changes in second-generation animals (hypoactivity of males and females on day 22 of life and hyperactivity of males on day 57 of life). Second-generation animals exhibited no gender differences in body weight and horizontal and vertical locomotor activity.