El sistema cardiovascular y la exposición a gran altitud: desde la adaptación a la enfermedad. Parte I

Hypoxia causes pulmonary vasoconstriction. Regional hypoxic vasoconstriction improves the matching of perfusion to alveolar ventilation. Global hypoxic vasoconstriction increases right ventricular afterload. The hypoxic pulmonary pressor response is universal in mammals and in birds, but with considerable interspecies and interindividual variability. Chronic hypoxia induces pulmonary hypertension in proportion to initial vasoconstriction. Prolonged hypoxic exposure is also associated with an increase in red blood cell mass, which aggravates pulmonary hypertension by an increase in blood viscosity. Hypoxic pulmonary hypertension in humans is usually mild to moderate, but pulmonary vascular pressure-flow relationships are steep, which corresponds to a substantial afterload on the right ventricle during exercise. A partial recovery of 10-25% of the hypoxia-induced decrease in maximal oxygen uptake has been reported with intake-specific pulmonary vasodilating interventions. Hypoxia has been reported to decrease myocardial fibre contractility in vitro. However, the acutely hypoxic right ventricle remains able to preserve the coupling of its contractility to increased afterload in intact animals. Echocardiographic studies of the right ventricle in healthy hypoxic human subjects show altered diastolic function, but systolic function that is preserved or even increased acutely and slightly depressed chronically. These findings are more pronounced in patients with chronic mountain sickness. Their clinical significance remains incompletely understood. Almost no imaging studies of right ventricular function have been reported in a minority of subjects who develop severe pulmonary hypertension and clinical right ventricular failure in hypoxia. No imaging studies of right ventricular function during hypoxic exercise in normal subjects are yet available. Thus, while it is plausible that the right ventricle limits exercise capacity in hypoxia, this still needs to be firmly established.

Currently, launching a satellite into orbit is plausible only for organizations with multi-million dollar budgets and requires three or more years for development and qualification. Small satellites traveling as secondary payloads on regularly scheduled launches provide access to space at a fraction of the cost and in a fraction of the time. However, a modular adaptable satellite container can significantly reduce cost and development schedule. By sealing and pressurizing the container to maintain an earthlike environment in orbit, a payload of unmodified terrestrial electronics can be integrated and launched in a matter of weeks. Such a container, SCUTE (Sealed Container for Universal Terrestrial Equipment), can provide a ride to space for K-12 educational experiments, research projects or electronic sensing and communication equipment. SCUTE can also enable military surveillance missions to be accomplished in a timely manner. A conceptual design investigation for SCUTE has been performed including benchmark designs and preliminary structural, thermal, and pressure loss analyses. This paper presents multiple design concepts for four different SCUTE attributes. The leading concept selected for thermal management is a forced air convection thermal switch (FACTS). Other SCUTE attributes selected for simplicity and compatibility with FACTS are the box configuration, an adjustable payload mounting shelf, and the use of air as the working fluid. These selected concepts are recommended for a preliminary design phase and more detailed analysis to make SCUTE a viable option for rapid and inexpensive access to space.

The present study was undertaken to determine the fat indices in high and low altitude populations in Southwestern Saudi Arabia. Measurement of weight, height, mid-upper arm circumference, mid-upper arm muscle area, and skinfold thickness over the triceps region in 261 males living at high altitude (3150 meters above sea level) and 237 males living at low altitude (500 meters above sea level) in Southern Saudi Arabia are reported. The assessment of fatness by calculation of percent body weight is supported by correlation of triceps skinfold thickness with body mass index (BMI). In both high- and lowlanders the triceps skinfold thickness has significant correlation with BMI (P<0.001 for both). BMI also showed significant correlations with body weight, mid-upper arm circumference and mid-upper arm muscle area (P<0.001 for all). The findings show that the use of skinfold thickness in the prediction of degree of fatness in both groups seems to be a practical and useful method. However, it appears that there is a need for densitometric studies among Saudi populations to enable the derivation of valid regression equations for the calculation of body fat from skinfold thickness measurements. In the absence of skinfold measurements the BMI appeared to be a reliable indicator for assessment of body fat in Saudi high- and lowlanders.

IntroductionHigh altitude hypoxia is believed to be experienced at elevations of more than 2500 meters above sea level. Several studies have shed light on the biochemical aspects of high altitude acclimatization, where participants were sojourners to the high altitude from low altitude areas. However, information regarding the difference between the high altitude adapted Tibetans living at high altitude and their counterparts who reside at low altitude are lacking. To understand this, we have measured various hematological parameters in the Tibetan populations, who are residing in both high and low altitudes in India.MethodsA total of 168 individuals (79 from high altitude (≥4500 meters) and 89 from low altitude (~850 meters) were recruited for this study. Hematological parameters such as red blood cells (RBC) count, hematocrit (HCT), hemoglobin concentration (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) were measured from the individuals from high and low altitudes. Serum erythropoietin (EPO) was measured by ELISA. Statistical analyses were performed to compare data from both of the altitudes. Gender-wise comparison of data was reported. Correlation analysis was performed within relevant parameters.ResultsHighly significant differences (p <0.0001) between high and low altitude Tibetans were detected in RBC count, HCT, Hb, MCHC in both males and females and in MCV in females. In the case of MCHC, however, age and BMI were potential confounders. Nominally significant differences (p <0.05) were detected in MCV and MCH within males. No significant difference in serum EPO level was found between altitude groups, in any gender. No significant correlation was found between serum EPO with Hb as well as serum EPO with HCT.DiscussionOur study explores significantly lower RBC count, HCT, Hb, MCH, MCHC and higher MCV in long-term Tibetan residents living at low altitude compared to their high altitude counterparts, which is likely due to the outcome of hematological adaptation to a relatively hyperoxic environment in low altitude areas.

reports of a relationship between altitude and circulating levels of leptin suggest a possible role of hypoxia in leptin regulation. However, studies on the changes in plasma leptin levels at altitude are controversial, with some showing an increase and others suggesting no change or a fall in these

This review focuses on the effects of altitude exposure from 1 to several days or weeks as occurs in tourists, trekkers, and mountaineers who visit high altitude and normally reside near sea level. We briefly review the acute physiological adjustments and early acclimatization that occur in the cardiovascular system and the lungs of healthy individuals. These ensure life-sustaining oxygen delivery to the tissues despite a reduction in the partial pressure of inspired oxygen between 20% and 60% at 2500 and 8000 m, respectively. One of the acute adjustments, hypoxic pulmonary vasoconstriction (HPV), may be disadvantageous in those with a vigorous response and lead to 2 potentially lethal illnesses, high-altitude pulmonary edema (HAPE) and subacute mountain sickness (SAMS), which we present in more detail. Finally, on the basis of knowledge about the acute physiological adjustments and acclimatization and, when available, a review of the literature, we discuss the high-altitude tolerance of patients with coronary artery disease, congestive heart failure, arrhythmias, systemic hypertension, and pulmonary hypertension. ### Circulation The major effects of acute hypoxia on the heart and lung are shown in Figure 1. Hypoxia directly affects the vascular tone of the pulmonary and systemic resistance vessels and increases ventilation and sympathetic activity via stimulation of the peripheral chemoreceptors.1 Interactions occur between the direct effects of hypoxia on blood vessels and the chemoreceptor-mediated responses in the systemic and pulmonary circulation. Figure 1. Effects of hypoxia on systemic and pulmonary circulation. Unraveling the underlying mechanisms of the hypoxic vasodilatation of systemic arterioles is an active area of research. Several mechanisms appear to regulate local oxygen delivery according to the needs of the tissues2,3; for instance, the release of ATP from red blood cells and the generation of NO by various ways appear to regulate local oxygen delivery according to the needs …

Ferrarini, Giovanni, Mattia Canevari, Valeria Azzini, Piergiuseppe Agostoni, Beatrice Pezzuto, and Carlo Vignati. Physiological responses to acute hypobaric and normobaric hypoxia: Differences in maximal exercise and clinical impact. High Alt Med Biol. 00:00-00, 2026.-Hypoxia, defined by inspired partial pressure of oxygen (PiO2) <150 mmHg, has been extensively studied in conditions of both reduced barometric pressure (hypobaric hypoxia, HH) and reduced inspired fraction of oxygen (FiO2) at sea level (normobaric hypoxia, NH). Traditionally considered interchangeable, mounting evidence indicates that HH and NH elicit distinct cardiovascular, ventilatory, and gas-exchange responses during physical effort, likely due to factors beyond PiO2, including air density, alveolar gas composition, exercise modality, and the age and sex of the individual performing the effort. A thorough understanding of how different hypoxic modalities affect exercise responses provides fundamental insights into human physiology and pathophysiology under extreme conditions, with practical implications for sports medicine and athletic training, as well as for patients with pathologies potentially influenced by hypoxia dealing with high altitude. This narrative review synthesizes current evidence on the differential effects of HH and NH on exercise responses, with an emphasis on maximal exercise capacity and underlying the physiological mechanisms regarding cardiovascular function, ventilatory adaptation, and gas-exchange responses, also outlining the implications for athletes, clinical populations (heart failure, chronic obstructive pulmonary disease, pulmonary hypertension), and altitude medicine.

There is no doubt that many hypoxic conditions or prolonged exposures to altitude result in "biological costs of hypoxic adaptations that outweigh their benefits" (1), particularly in endurance athletes exposed to (a) exercise-induced arterial hypoxemia leading to a larger decrease in V˙O2max and aerobic endurance, (b) increased sympathetic activity and decreased baroreflex sensitivity, and (c) increased pulmonary arterial pressure. There is also no doubt that sleeping in moderate altitude (2000–3000 m) as performed by the athletes using either live high-train high (LHTH) or live high-train low (LHTL) methods leads to periodic breathing, intermittent hypoxia (IH), and increase in desaturation periods; for example, 3% oxygen desaturation index, but to a larger extent in hypobaric hypoxia (HH) (real altitude) than in normobaric hypoxia (NH) (simulated altitude), as shown at 2250 m (2). The three main questions debated in the present contrasting perspective are, however, different: Are there any evidences showing if the "counteracting maladaptation" (reported above) outweigh the benefits of the different hypoxic methods at short- or long-term in elite athletes? Are there any robust data supporting that hypoxic training is beneficial in elite athletes? Contradictory, are there robust data showing that hypoxic training is not beneficial in elite athletes? EVIDENCE OF "COUNTERACTING MALADAPTATION" OUTWEIGHING THE BENEFITS OF ALTITUDE TRAINING? Answering the first question is easy: as stated by Dempsey and Morgan (1), the "available evidence that predicts that the maladaptive responses (to hypoxic training/exposure or cyclical IH) would oppose or even erode the key adaptive performance-enhancing mechanisms elicited by physical training … are not verified yet." These concerns are, therefore, of interest but remain purely theoretical and speculative. Moreover, the severity of altitude recommended for both LHTL and LHTH methods (i.e., 2200–2500 m) (3,4) is too low for inducing high-altitude illnesses (acute mountain sickness, high altitude pulmonary, or cerebral edemas) (5). Finally, there is a growing literature showing that adequate monitoring of the responses/behavior of the athletes may limit some hypoxic-induced detrimental effects; illness, dehydration, or sympathetic-induced "fatigue" (3). For example, heart rate variability guided training is effective for limiting perceived fatigue during LHTL (6). A vast majority of elite endurance athletes and support staff utilized altitude training and considered hypoxia as "very important" (7). Would you trust your doctor not asking you how you feel after a treatment? Or worse, maintaining that the medication was harmful or ineffective if you feel better? STUDIES SUPPORTING THAT HYPOXIC TRAINING IS BENEFICIAL IN ELITE ATHLETES? From the original review by Wilber (8) that defined three models (LHTH, LHTL, and live low-train high [LLTH]) used in the resting state (IH exposure [IHE]) or during training sessions (intermittent hypoxic training [IHT]), the panorama of the hypoxic training methods utilized in sport has been largely updated in two directions: first, the possibility to combine different methods; for example, LHTL + IHT; second the development of new methods at high-intensity, potentially useful for intermittent (team-, racket- or combat sports) athletes (9,10). There are many articles (11) supporting the positive hematological effects of LHTH or LHTL as long the hypoxic dose is high enough. The increase in total hemoglobin mass (Hbmass) is estimated at a mean rate of 1.0% to 1.1% per 100 h of exposure in both NH and HH conditions (12,13). In a critical review (4), some relevant weaknesses or methodological limitations have been emphasized as the needs of better controlling the placebo effects with elite athletes; but the main conclusion was "LHTH and LHTL may increase exercise performance in some but certainly not in all athletes" and did not throw the baby out with the bathwater. Several confounding factors that may limit the Hbmass increase, such as the health (illness/injuries) status of the athlete (14), insufficient iron store/supplementation (15), insufficient hydration for compensating the increased respiratory water loss (hyperventilation) and diuresis (16), and insufficient energy (particularly carbohydrate) availability (16), are now clarified and thus better monitored on the field by the servicing physiologists who support athletes during altitude training camps. Importantly, hypoxic training is not limited to LHTH and LHTL anymore, and the recent implementation of innovative methods, such as repeated-sprint training in hypoxia (RSH), is an important step forward (17,18). Despite its novelty, RSH is of high interest in exercise physiology: with 25 experimental studies published in the 5-yr period (19) after the pionneer RSH article in 2013 (18), RSH is shown to be effective for improving repeated-sprint ability in intermittent (team—rugby, football, field hockey; racket (tennis), as well as endurance (cycling, cross-country ski) sports (for an updated review: [19]). Moreover, from a mechanistic point of view, RSH questions the nonhematological responses to hypoxia: The underlying mechanisms are specific to RSH and not observed neither with passive exposure to hypoxia nor in the other hypoxic methods utilizing lower training intensities. The transcriptional and vascular responses lead to improved behavior of fast-twitch fibers, notably via compensatory vasodilatation and faster rate of phosphocreatine resynthesis (18,20). To our knowledge, there is no maladaptation to RSH (e.g., impaired immune function) identified yet. STUDIES SUPPORTING THAT HYPOXIC TRAINING IS NOT BENEFICIAL IN ELITE ATHLETES? An interesting point of view that "altitude training does not convincingly increase exercise performance and should not be recommended to elite (endurance) athletes" (21) is not based on the "counteracting maladaptation" discussed above (point 1) but on the assumption that athletes with a high initial Hbmass value are close to a "ceiling" level and would, therefore, not increase Hbmass and maximal oxygen consumption (22). We had already the opportunity to state that some of the previous studies supporting this noneffectiveness of LHTL may come from inaccurate data coming from "noisy" (poor "signal-to-noise ratio") data with a relatively high typical error of Hbmass measurement (23). Furthermore, additional findings (24) confirmed that even athletes with high initial Hbmass value did benefit from a substantial increase (3%–4%) as long as the hypoxic dose was high enough (200–230 h at 2250 m). Recently, an additional study (25) on elite cross-country skiers performing LHTL with 26 nights at 2207 m (terrestrial altitude) did not show any additional effect on running economy, performance, oxidative muscle capacities, or lung diffusive capacity when compared with a LLTL group that trained up to 1500 m and slept at 1035 m. Unfortunately, there was no sea-level control group. Overall, it remains unclear if these authors are discussing the noneffectiveness of all hypoxic/altitude methods or if they restrict their concerns only to LHTL. If so, we concede that we could find an agreement because the superiority of LHTL over LHTH remains questionable, unclear, and probably overestimated. Regarding the effectiveness of RSH, only two studies of 25 did not report some positive outcomes (19). Although further work is requested on the underyling mechanisms and the optimal parameters specific to each sport, there is little doubt that this innovative method brings improvement in repeated-sprint ability (19), as now admitted by Prof. Lundby (http://www.worldrowing.com/photos-videos/videos/2018-world-rowing-coaches-conference-thursday 4:09:13 to 4:11:10). In conclusion, there are some maladaptative mechanisms related to altitude exposure but most are not relevant to the conditions (altitude severity, duration of exposure, …) and methods recommended and used by elite athletes. The altitude-induced erythropoeitic effects and improvement in oxygen transport capacity are observed in most athletes as long as the hypoxic dose is important enough. There are new effective hypoxic methods in intermittent sports. The robustness of most contradicting studies that reported a noneffectiveness of altitude training (LHTL only?) methods is questionable. RESPONSE TO SIEBENMANN AND DEMPSEY Siebenmann and Dempsey (26) argued that "the available evidence does not justify recommending any of the existing hypoxic training methods (LHTH, LHTL, or LLTH)." Despite our high respect for their work, our opponents' points are often confused, due to the use of many references not directly related to the topic and erroneous statements. LHTH We agree that there are not enough well-controlled studies on LHTH likely due to logistical difficulties and the impossibility of "double-blinding" the protocol. Our opponents mentioned the "only controlled" LHTH study by Rodriguez et al. (27) where the two groups of swimmers who lived for 4 wk and train permanently (Hi-Hi) or partly (Hi-HiLo) at 2320 m improved their aerobic performance (400-m freestyle) to a larger extent that the control group (3.3% and 4.7% vs 1.6%). However, at least two other controlled studies on LHTH have been published: Bonne et al. (28) reported an Hbmass increase (by 6.2%) in elite swimmers who lived and trained 3 to 4 wk between 2130 and 3094 m. This LHTH group tended to improve aerobic performance (3000-m freestyle) to a larger extent than a sea-level (SL) control group. Similarly, Mellerowicz et al. (29) showed that moderately trained athletes who performed 4 wk at 2020 m had a larger improvement in V˙O2max and aerobic performance (3000-m running) than a SL group. Cherry picking? It is known that hypoxic exposure induces an increase in hemoglobin mass (Hbmass) (14,27,28,30–33). This was also shown in a study by Siebenmann et al. (34) who reported a 5.3% increase after 4 wk at 3450 m of altitude. Interestingly, their findings are in line with the most common recommendations and practice for LHTH duration (2 to 4 wk, (35)) because the increase started after 12 d with a plateau after 20 to 24 d. Regarding the potential adverse impacts—called "maladaptation"—that altitude can exert (e.g., chemoreflex activation, pulmonary vasoconstriction, impaired sleep quality, and recovery), none has been shown in elite athletes, is therefore only speculative, and highlights areas for future research. LHTL In this section, our opponents reported only "three controlled LHTL studies using natural altitude." In the first study (32), despite a nonsignificant difference in training loads between groups, Hbmass increased by 4.4% and 4.1% in two LHTL groups who spent 18 d at 2250 m either in HH or in NH but remained unchanged in a control group. Moreover, the aerobic performance (3000-m running) was improved by 3.9% and 3.3% in the two LHTL groups and only by 2.1% in the control group. The second study (27) protocol was misunderstood by our opponents because the Hi-HiLo group trained only occasionally at low altitude. Finally, one may question the relevance of the third study (25) because there was no SL control group (36). One may question why our opponents did not extend their search to all LHTL studies? Cherry picking again? For example, in team-sport players who spent 14 d of LHTL at 3000 m, aerobic performance (YoYoR2) and Hbmass were significantly improved, whereas no change occurred in the SL control group (33). Our opponents do not recommend altitude/hypoxic training in elite athletes. Fine! But did they provide any evidence of deleterious effects of LHTH or LHTL reported in elite athletes? Or is their position purely theoretical? To our knowledge, there are no controlled studies where LHTH or LHTL led to performance impairment, when compared with a SL group. We concede that one of the confounding factor that remains debated is the definition of the optimal hypoxic dose and optimal altitude for erythropoietic responses: most of the LHTH studies conducted at low altitude (<1900 m) (37,38)—but not all (39)—did not lead to higher change in V˙O2max or performance than the control group. With other experts in the field, we do recommend an altitude between 2200 and 2500 m (3,35,40). Overall, we believe that the skepticism about the effectiveness of LHTL strategies comes originally from inaccurate Hbmass measurement (41–43), as stated by eminent researchers (13,44), working daily with elite athletes (23). However, we concede that the sometimes claimed superiority of LHTL over LHTH deserves further investigation. From a practical point of view, the optimal strategy remains likely to combine the different hypoxic training methods depending of the training phases and athlete/sport characteristics (33,35) to optimize the benefits and minimize the risks associated to altitude training. LLTH Among the various LLTH methods, RSH has gained in popularity with >26 articles published by various research groups in the last 5 yr (19), confirming its putative benefits displayed in this meta-analysis (45). Regarding the point raised by our opponents on the use of SE from one study (46), Comprehensive Meta-Analysis Software (Biostat, Inc., Englewood, NJ) allows user to create multidata entry formats, permitting for example to report SD, odds ratios, or 95% confidence intervals (in this case, SE is most useful as a means of calculating a confidence interval than SD (47)). Of note, recalculating SD remains possible using single unknown equation (SE = SD/√[sample size]) and might be more relevant than estimation of variance "from sample size and SD" or "from SD alone" (48,49). It is evident that detecting any publication bias is of paramount importance to avoid incorrect conclusions. In this view, Begg and Mazumdar's rank correlation, Egger's regression tests, and asymmetry examination of funnel plots were reported in (45). It is also obviously interesting to consider studies that did not report any RSH benefits to better define protocols. Unfortunately, the outcome of the only crossover study reporting no additional performance benefits of RSH (50) is likely due to methodological shortcomings, with too many tests after the intervention, precluding subjects to perform maximally. CONCLUDING STATEMENT The accumulating body of scientific evidences and the increasing interest/utilization by elite athletes for the different methods of altitude training are coherent. Because hypoxic training is beneficial if adequately performed and monitored, we do recommend its use by elite athletes. Expertise in this field requires understanding the pros and cons of each method (LHTH, LHTL, or LLTH) and how to combine them.

High altitude brings a great physiological change in human beings, both during short-term exposure and in lifelong residents, especially in the cardiovascular system. Hypoxia notably induces pulmonary vasoconstriction, thus resulting in a moderate increase in pulmonary arterial pressure. Acclimatized inhabitants exhibit lower pulmonary pressure and better exercise capacity than lowlanders during short-term high-altitude exposure. Rapid ascent to high altitude without adequate acclimatization can cause high-altitude pulmonary edema in susceptible individuals, with a rapid increase in pulmonary pressure. Cardiac output increases initially following acute high-altitude exposure and returns to normal as at sea level after a few days of acclimatization. Ventricular volumes at high altitude change consistently with decreases in plasma volume. Left ventricular systolic function is enhanced after acute high-altitude exposure and during chronic acclimatization. However, there are controversies on whether right ventricular systolic function is preserved or decreases after high-altitude exposure, probably due to variable hypoxic pulmonary vasoconstriction. High altitude induces altered ventricular diastolic patterns. Recently, a new perspective has emerged, whereby ventricular intrinsic relaxation is not impaired, as assessed by untwisting through speckle-tracking imaging. Persistent hypoxic pulmonary hypertension probably induced right ventricular dilation and hypertrophy, and even right heart failure, described as high-altitude heart diseases. Descent to lower altitude should be the best treatment for them, and potential pharmacological agents majorly focus on the inhabitation of pulmonary vasoconstriction, such as phosphodiesterase-5 inhibitors and endothelin receptor antagonists. Evidence on the risks of high-altitude exposure for patients with previous cardiovascular diseases is limited, and thus they should be prudent when ascending to high altitude. Further randomized large-scale studies are needed to explore cardiac performance at high altitudes and provide more evidence for the prevention and clinical management of medical complications at high altitude.

We sought to determine the isolated and combined influence of hypovolaemia and hypoxic pulmonary vasoconstriction on the decrease in left ventricular (LV) function and maximal exercise capacity observed under hypobaric hypoxia. We performed echocardiography and maximal exercise tests at sea level (344m), and following 5-10days at the Barcroft Laboratory (3800m; White Mountain, California) with and without (i) plasma volume expansion to sea level values and (ii) administration of the pulmonary vasodilatator sildenafil in a double-blinded and placebo-controlled trial. The high altitude-induced reduction in LV filling and ejection was abolished by plasma volume expansion but to a lesser extent by sildenafil administration; however, neither intervention had a positive effect on maximal exercise capacity. Both hypovolaemia and hypoxic pulmonary vasoconstriction play a role in the reduction of LV filling at 3800m, but the increase in LV filling does not influence exercise capacity at this moderate altitude. We aimed to determine the isolated and combined contribution of hypovolaemia and hypoxic pulmonary vasoconstriction in limiting left ventricular (LV) function and exercise capacity under chronic hypoxaemia at high altitude. In a double-blinded, randomised and placebo-controlled design, 12 healthy participants underwent echocardiography at rest and during submaximal exercise before completing a maximal test to exhaustion at sea level (SL; 344m) and after 5-10days at 3800m. Plasma volume was normalised to SL values, and hypoxic pulmonary vasoconstriction was reversed by administration of sildenafil (50mg) to create four unique experimental conditions that were compared with SL values: high altitude (HA), Plasma Volume Expansion (HA-PVX), Sildenafil (HA-SIL) and Plasma Volume Expansion with Sildenafil (HA-PVX-SIL). High altitude exposure reduced plasma volume by 11% (P<0.01) and increased pulmonary artery systolic pressure (19.6±4.3 vs. 26.0±5.4, P<0.001); these differences were abolished by PVX and SIL respectively. LV end-diastolic volume (EDV) and stroke volume (SV) were decreased upon ascent to high altitude, but were comparable to sea level in the HA-PVX trial. LV EDV and SV were also elevated in the HA-SIL and HA-PVX-SIL trials compared to HA, but to a lesser extent. Neither PVX nor SIL had a significant effect on the LV EDV and SV response to exercise, or the maximal oxygen consumption or peak power output. In summary, at 3800m both hypovolaemia and hypoxic pulmonary vasoconstriction contribute to the decrease in LV filling, but restoring LV filling does not confer an improvement in maximal exercise performance.

High altitude is known to have a significant impact on human physiology and health, therefore, understanding its relationship with quality of life is an important research area. This study compared the quality of life (QOL) in older adults living in high and low altitude areas, and examined the independent correlates of QOL in those living in a high altitude area. Older adults living in three public nursing homes in Xining (high altitude area) and one public nursing home in Guangzhou (low altitude area) were recruited. The WHOQOL-BREF was used to measure the QOL. 644 older adults (male: 39.1%) were included, with 207 living in high altitude and 437 living in low altitude areas. After controlling for the covariates, older adults living in the high altitude area had higher QOL in terms of physical (P = 0.035) and social domains (P = 0.002), but had lower QOL in psychological (P = 0.009) domain compared to their counterparts living in the low altitude area. For older adults living in the high altitude area, smoking status was associated with higher social QOL (P = 0.021), good financial status was associated with higher physical QOL (P = 0.035), and fair or good health status was associated with higher physical (p < 0.001) and psychological QOL (P = 0.046), while more severe depressive symptoms were associated with lower QOL. Appropriate interventions and support to improve depressive symptoms and both financial and health status should be developed for older adults living in high altitude areas to improve their QOL.

BackgroundHypoxia-induced pulmonary hypertension (HPH) is one of the fatal pathologies developed under hypobaric hypoxia and eventually leads to right ventricular (RV) remodeling and RV failure. Clinically, the mortality rate of RV failure caused by HPH is high and lacks effective drugs. Xinyang Tablet (XYT), a traditional Chinese medicine exhibits significant efficacy in the treatment of congestive heart failure and cardiac dysfunction. However, the effects of XYT on chronic hypoxia-induced RV failure are not clear.MethodsThe content of XYT was analyzed by high-performance liquid chromatography-tandem mass spectrometry (HPLC–MS). Sprague–Dawley (SD) rats were housed in a hypobaric chamber (equal to the parameter in altitude 5500 m) for 21 days to obtain the RV remodeling model. Electrocardiogram (ECG) and hemodynamic parameters were measured by iWorx Acquisition & Analysis System. Pathological morphological changes in the RV and pulmonary vessels were observed by H&E staining and Masson’s trichrome staining. Myocardial apoptosis was tested by TUNEL assay. Protein expression levels of TNF-α, IL-6, Bax, Bcl-2, and caspase-3 in the RV and H9c2 cells were detected by western blot. Meanwhile, H9c2 cells were induced by CoCl2 to establish a hypoxia injury model to verify the protective effect and mechanisms of XYT. A CCK-8 assay was performed to determine the viability of H9c2 cells. CoCl2-induced apoptosis was detected by Annexin-FITC/PI flow cytometry and Hoechst 33,258 staining.ResultsXYT remarkably improved RV hemodynamic disorder and ECG parameters. XYT attenuated hypoxia-induced pathological injury in RV and pulmonary vessels. We also observed that XYT treatment decreased the expression levels of TNF-α, IL-6, Bax/Bcl-2 ratio, and the numbers of myocardial apoptosis in RV. In H9c2 myocardial hypoxia model, XYT protected H9c2 cells against Cobalt chloride (CoCl2)-induced apoptosis. We also found that XYT could antagonize CoCl2-induced apoptosis through upregulating Bcl-2, inhibiting Bax and caspase-3 expression.ConclusionsWe concluded that XYT improved hypoxia-induced RV remodeling and protected against cardiac injury by inhibiting apoptosis pathway in vivo and vitro models, which may be a promising therapeutic strategy for clinical management of hypoxia-induced cardiac injury.

High altitude (hypobaric hypoxia) triggers several mechanisms to compensate for the decrease in oxygen bioavailability. One of them is pulmonary artery vasoconstriction and its subsequent pulmonary arterial remodeling. These changes can lead to pulmonary hypertension and the development of right ventricular hypertrophy (RVH), right heart failure (RHF) and, ultimately to death. The aim of this review is to describe the most recent molecular pathways involved in the above conditions under this type of hypobaric hypoxia, including oxidative stress, inflammation, protein kinases activation and fibrosis, and the current therapeutic approaches for these conditions. This review also includes the current knowledge of long-term chronic intermittent hypobaric hypoxia. Furthermore, this review highlights the signaling pathways related to oxidative stress (Nox-derived O2.- and H2O2), protein kinase (ERK5, p38α and PKCα) activation, inflammatory molecules (IL-1β, IL-6, TNF-α and NF-kB) and hypoxia condition (HIF-1α). On the other hand, recent therapeutic approaches have focused on abolishing hypoxia-induced RVH and RHF via attenuation of oxidative stress and inflammatory (IL-1β, MCP-1, SDF-1 and CXCR-4) pathways through phytotherapy and pharmacological trials. Nevertheless, further studies are necessary.

Excerpt Continuous exposure to a high-altitude environment, where the lowered partial pressure of the oxygen in the inspired air originates a certain degree of hypoxia, demands some adaptative mech...

The domestication of non-timber forest species (NTFS) is receiving increasing attention from developing economies. However, little is known about the selection of NTFS in Nepal for commercial uses. Sixteen selection criteria were developed and NTFS were ranked for community and private plantations in both low altitude and high altitude areas of Makawanpur district, Nepal, by workshops of multiple NTFS stakeholders. The rigorous scoring of 12 ecologically screened NTFS against the 16 selection criteria revealed that kurilo and sarpagandh are highly preferred NTFS for low altitude areas whereas chiraito and jatamanshi are highly preferred for high altitude. This finding coincides with the general perception of participants and contemporary literature. These are the species being rapidly depleted from the natural forests. Rapid decline of valuable species creates strong motivation from stakeholders for planting them on community and private land.