High Altitude Control Research Articles

Curcumin-mediated enhancement of lung barrier function in rats with high-altitude-associated acute lung injury via inhibition of inflammatory response

BackgroundExposure to a hypobaric hypoxic environment at high altitudes can lead to lung injury. In this study, we aimed to determine whether curcumin (Cur) could improve lung barrier function and protect against high-altitude-associated acute lung injury.MethodsTwo hundred healthy rats were randomly divided into standard control, high-altitude control (HC), salidroside (40 mg/kg, positive control), and Cur (200 mg/kg) groups. Each group was further divided into five subgroups. Basic vital signs, lung injury histopathology, routine blood parameters, plasma lactate level, and arterial blood gas indicators were evaluated. Protein and inflammatory factor (tumor necrosis factor α (TNF-α), interleukin [IL]-1β, IL-6, and IL-10) concentrations in bronchoalveolar lavage fluid (BALF) were determined using the bicinchoninic acid method and enzyme-linked immunosorbent assay, respectively. Inflammation-related and lung barrier function-related proteins were analyzed using immunoblotting.ResultsCur improved blood routine indicators such as hemoglobin and hematocrit and reduced the BALF protein content and TNF-α, IL-1β, and IL-6 levels compared with those in the HC group. It increased IL-10 levels and reduced pulmonary capillary congestion, alveolar hemorrhage, and the degree of pulmonary interstitial edema. It increased oxygen partial pressure, oxygen saturation, carbonic acid hydrogen radical, and base excess levels, and the expression of zonula occludens 1, occludin, claudin-4, and reduced carbon dioxide partial pressure, plasma lactic acid, and the expression of phospho-nuclear factor kappa.ConclusionsExposure to a high-altitude environment for 48 h resulted in severe lung injury in rats. Cur improved lung barrier function and alleviated acute lung injury in rats at high altitudes.

Nanocurcumin attenuates pyroptosis and inflammation through inhibiting NF-κB/GSDMD signal in high altitude-associated acute liver injury.

Exposure to a hypobaric hypoxic environment at high altitudes can lead to liver injury, and mounting evidence indicates that pyroptosis and inflammation play important roles in liver injury. Curcumin (Cur) can inhibit pyroptosis and inflammation. Therefore, our purpose here was to clarify the mechanism underlying the protective effect of nanocurcumin (Ncur) and Cur in a rat model of high altitude-associated acute liver injury.Eighty healthy rats were selected and exposed to different altitudes (6000 or 7000 m) for 0, 24, 48, or 72 h. Fifty normal healthy rats were divided into normal control, high-altitude control, salidroside (40 mg/kg [Sal-40]), Cur (200 mg/kg [Cur-200]), and Ncur (25 mg/kg [Ncur-25]) groups and exposed to a high-altitude hypobaric hypoxic environment (48 h, 7000 m). Serum-liver enzyme activities (alanine transaminase, aspartate transaminase, and lactate dehydrogenase were detected and histopathology of liver injury was evaluated by hematoxylin and eosin staining, and inflammatory factors were detected in liver tissues by enzyme-linked immunosorbent assays. Pyroptosis-associated proteins (gasdermin D, gasdermin D N-terminal [GSDMD-N], pro-Caspase-1, and cleaved-Caspase-1 [cleaved-Casp1]) and inflammation-associated proteins (nuclear factor-κB [NF-κB], phospho-NF-κB [P-NF-κB], and high-mobility group protein B1 [HMGB1]) levels were analyzed by immunoblotting. Ncur and Cur inhibited increased serum-liver enzyme activities, alleviated liver injury in rats caused by high-altitude hypobaric hypoxic exposure, and downregulated inflammatory factors, including tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and IL-18, in rat liver tissues. The level of P-NF-κB, GSDMD-N, cleaved-Casp1, and HMGB1 in rat liver tissues increased significantly after high-altitude exposure. Ncur and Cur downregulated P-NF-κB, GSDMD-N, cleaved-Casp-1, and HMGB1. Ncur and Cur may inhibit inflammatory responses and pyroptosis in a rat model of high altitude-associated acute liver injury.

Tyrosine phosphorylation of band 3 impairs the storage quality of suspended red blood cells in the Tibetan high-altitude polycythemia population

Due to environmental hypoxia on the Tibetan Plateau, local residents often exhibit a compensative increase in hemoglobin concentration to maintain the body’s oxygen supply. However, increases in hemoglobin and hematocrit (Hct) pose a serious challenge to the quality of stored suspended red blood cells (SRBCs) prepared from the blood of high-hemoglobin populations, especially populations at high altitude with polycythemia in Tibet. To explore the difference in storage quality of SRBCs prepared from plateau residents with a high hemoglobin concentration, blood donors were recruited from Tibet (> 3600 m) and Chengdu (≈ 500 m) and divided into a high-altitude control (HAC) group, high-altitude polycythemia (HAPC) group and lowland control (LLC) group according to their hemoglobin concentration and altitude of residence. The extracellular acidification rate (ECAR), pyruvate kinase (PK) activity and band 3 tyrosine phosphorylation were analyzed on the day of blood collection. Then, whole-blood samples were processed into SRBCs, and storage quality parameters were analyzed aseptically on days 1, 14, 21 and 35 of storage. Overall, we found that tyrosine 21 phosphorylation activated glycolysis by releasing glycolytic enzymes from the cytosolic domain of band 3, thus increasing glucose consumption and lactate accumulation during storage, in the HAPC group. In addition, band 3 tyrosine phosphorylation impaired erythrocyte deformability, accompanied by the highest hemolysis rate in the HAPC group, during storage. We believe that these results will stimulate new ideas to further optimize current additive solutions for the high-hemoglobin population in Tibet and reveal new therapeutic targets for the treatment of HAPC populations.

The Characteristics of Sleep Apnea in Tibetans and Han Long-Term High Altitude Residents.

PurposeObstructive sleep apnea (OSA) is common both at low and high altitude. Since adaptations to high altitude and respiratory control may differ among Tibetans and Hans, we compared characteristics of sleep-disordered breathing in the two ethnic groups at high altitude.Materials and MethodsThis was a prospective observational study including 86 Tibetan and Han long-term (>5 years) high altitude residents with chief complaints of snoring and/or witnessed apnea underwent clinical evaluation and polysomnography at 3200 meters in Shangri-La, China.ResultsIn 42 Tibetans, 38 men, median (quartiles) age was 50.0 (41.0; 56.0)y, total apnea/hypopnea index (AHI) 53.9 (32.0; 77.5)/h, obstructive AHI 51.0 (28.0; 72.2)/h and central AHI 1.5 (0.2; 3.1)/h. In 44 Hans, 32 men, median (quartiles) age was 47.0 (43.5; 51.0)y, total AHI 22.2 (12.8; 39.2)/h, obstructive AHI 17.7 (12.0; 33.0)/h and central AHI 2.4 (0.5; 3.4)/h (p < 0.001 total and obstructive AHI vs Tibetans). In Tibetans, mean nocturnal oxygen saturation was lower [median 85.0 (83.0; 88.0)% vs 88.5 (87.0; 90.0)%] and obstructive apnea and hypopnea duration was longer [22.0 (19.6; 24.8) sec vs 18.3 (16.7; 20.6) sec] than in Hans (all p < 0.001). In regression analysis, Tibetan ethnicity, neck circumference and high-altitude living duration were the predictors of total AHI. We also found that with every 10/h increase in total AHI, there were an approximately 0.9 beat/min and 0.8 beat/min increase in mean heart rate during rapid eye movement (REM) and non-REM sleep and 1.9 mmHg and 2.0 mmHg increase in evening and morning systolic blood pressure.ConclusionOur data suggest that Tibetans presented more severe obstructive sleep apnea, hypoxemia and longer apnea duration compared to Hans at 3200 meters, which was correlated with higher heart rate and blood pressure suggesting a greater cardiovascular risk.

Aberrant promoter hypermethylation regulates thrombomodulin in high altitude induced deep vein thrombosis

BackgroundDNA methylation regulates gene expression by inhibiting transcription factor binding to promoter and regulatory regions. Acute hypoxia during altitude exposure is associated with decreased natural anticoagulants and morbid thrombotic events. Thrombomodulin (TM) is a high affinity thrombin binding receptor protein, vital for vascular homeostasis. The purpose of this study is to determine gene expression regulation via methylation of TM gene in high altitude hypoxia induced deep vein thrombosis (DVT) patients. Materials and resultsPercent 5-methyl cytosine analysis showed increased methylation in high altitude DVT patients (HAP) as compared to high altitude control (HAC) and seal level control (Control) subjects, while TM protein and mRNA levels were decreased in high altitude DVT patients as compared to other two groups. Bisulfite sequencing analysis indicated increased methylation in TM promoter in high altitude DVT patients compared to high altitude controls. Flow cytometry analysis showed decreased TM expression in hypoxia induced primary human umbilical vein endothelial cells (HUVECs). Treatment with specific DNA methyltransferase (DNMT) inhibitor-decitabine during hypoxia, restored TM expression. in vitro global methylation assay showed increased methylation in hypoxia group. Specific concentration of decitabine in hypoxia decreased global methylation showing a direct correlation between DNMTs and methylation. Selective dose of decitabine restored TM levels in HUVECs. DNMT1 and DNMT3B proteins showed to mediate the overall expression of TM. ConclusionTM emerged as a potential candidate for methylation in high altitude DVT patients, regulated by hypoxia-induced epigenetic mechanism. Hypoxia culminates in methylation of DNA sequences in the promoter region of TM gene and increased the expression of DNMT1 and DNMT3B per se in primary HUVECs. Critical DNA methylation events were found to be compromised in high altitude DVT patients.

Fetal growth and spontaneous preterm birth in high-altitude pregnancy: A systematic review, meta-analysis, and meta-regression.

To understand the relationship between birth weight and altitude to improve health outcomes in high-altitude populations, to systematically assess the impact of altitude on the likelihood of low birth weight (LBW), small for gestational age (SGA), and spontaneous preterm birth (sPTB), and to estimate the magnitude of reduced birth weight associated with altitude. PubMed, OvidEMBASE, Cochrane Library, Medline, Web of Science, and clinicaltrials.gov were searched (from inception to November 11, 2020). Observational, cohort, or case-control studies were included if they reported a high altitude (>2500m) and appropriate control population. Of 2524studies identified, 59 were included (n=1604770 pregnancies). Data were abstracted according to PRISMA guidelines, and were pooled using random-effects models. There are greater odds of LBW (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.33-1.62, P<0.001), SGA (OR 1.88, 95% CI 1.08-3.28, P=0.026), and sPTB (OR 1.23, 95% CI 1.04-1.47, P=0.016) in high- versus low-altitude pregnancies. Birth weight decreases by 54.7g (±13.0g, P<0.0001) per 1000 m increase in altitude. Average gestational age at delivery was not significantly different. Globally, the likelihood of adverse perinatal outcomes, including LBW, SGA, and sPTB, increases in high-altitude pregnancies. There is an inverse relationship between birth weight and altitude. These findings have important implications for the increasing global population living at altitudes above 2500m.

Transcriptome Profiling Reveals the Endogenous Sponging Role of LINC00659 and UST-AS1 in High-Altitude Induced Thrombosis.

The pathophysiology of deep vein thrombosis (DVT) is considered as multifactorial, where thrombus formation is an interplay of genetic and acquired risk factors. Little is known about the expression profile and roles of long noncoding RNAs (lncRNAs) in human subjects developing DVT at high altitude. Using RNAseQ, we compared peripheral blood mRNA and lncRNA expression profile in human high-altitude DVT (HA-DVT) patients with high-altitude control subjects. We used DESeq to identify differentially expressed (DE) genes. We annotated the lncRNAs using NONCODE 3.0 database. In silico putative lncRNA-miRNA association study unravels the endogenous miRNA sponge associated with our candidate lncRNAs. These findings were validated by small-interfering RNA (siRNA) knockdown assay of the candidate lncRNAs conducted in primary endothelial cells. We identified 1,524 DE mRNAs and 973 DE lncRNAs. Co-expressed protein-coding gene analysis resulted in a list of 722 co-expressed protein-coding genes with a Pearson correlation coefficients >0.7. The functional annotation of co-expressed genes and putative proteins revealed their involvement in the hypoxia, immune response, and coagulation cascade. Through its miRNA response elements to compete for miR-143 and miR-15, lncRNA-LINC00659 and UXT-AS1 regulate the expression of prothrombotic genes. Furthermore, in vitro RNA interference (siRNA) simultaneously suppressed lncRNAs and target gene mRNA level. This transcriptome profile describes novel potential mechanisms of interaction between lncRNAs, the coding genes, miRNAs, and regulatory transcription factors that define the thrombotic signature and may be used in establishing lncRNAs as a biomarker in HA-DVT.

Continuous Multi-Angle Remote Sensing and Its Application in Urban Land Cover Classification

Because of the limitations of hardware devices, such as the sensors, processing capacity, and high accuracy altitude control equipment, traditional optical remote sensing (RS) imageries capture information regarding the same scene from mostly one single angle or a very small number of angles. Nowadays, with video satellites coming into service, obtaining imageries of the same scene from a more-or-less continuous array of angles has become a reality. In this paper, we analyze the differences between the traditional RS data and continuous multi-angle remote sensing (CMARS) data, and unravel the characteristics of the CMARS data. We study the advantages of using CMARS data for classification and try to capitalize on the complementarity of multi-angle information and, at the same time, to reduce the embedded redundancy. Our arguments are substantiated by real-life experiments on the employment of CMARS data in order to classify urban land covers while using a support vector machine (SVM) classifier. They show the superiority of CMARS data over the traditional data for classification. The overall accuracy may increase up to about 9% with CMARS data. Furthermore, we investigate the advantages and disadvantages of directly using the CMARS data, and how such data can be better utilized through the extraction of key features that characterize the variations of spectral reflectance along the entire angular array. This research lay the foundation for the use of CMARS data in future research and applications.

Diagnostic potential of circulating micro RNA hsa-miR-320 in patients of high altitude induced deep vein thrombosis: An Indian study

IntroductionVenous thrombo-embolism (VTE) is the third leading cardiovascular disease in world. Although, onset of VTE is linked to several established genetic and acquired risk factors, exposure to high altitude (HA) poses an additional and independent risk factor. There is a need for reliable molecular marker for early and accurate diagnosis of VTE. Micro RNAs (MiRNAs) have recently emerged as class of promising biomarkers in various diseases. Present study aimed to investigate diagnostic potential of selected miRNAs for HA induced VTE (HA-VTE). MethodBlood was collected from four group of subjects; sea level control, sea level VTE patients, high altitude control and high altitude VTE patients. Five potential miRNAs were investigated by quantitative real-time (qRT-PCR) profiling using specific miRNA assays and comparisons were done across groups. We further examined role of differentially expressed miRNAs in regulating genes of pathways involved in VTE and HA induced hypoxic stress using in-silico bioinformatics tools. ResultsOur results showed that miRNA levels of hsa-miR-320 were significantly up-regulated in patients of VTE both at sea level as well HA in comparison with respective controls. Also, hsa-miR-195 and hsa-miR-103a showed significant up-regulation in VTE patients at sea level. Further, in-silico analysis demonstrated that hsa-miR-320 regulates a large number of VTE-linked and HA-hypoxia linked pathways. ConclusionThe present study demonstrated for the first time that hsa-miR-320 plays a key role in pathogenesis of VTE during high altitude induced hypoxic exposure. Also, our results showed that hsa-miR-195 and hsa-miR-103a play an important role in VTE pathophysiology at sea level.

Abstract 653: The Long Noncoding RNA Landscape of the High Altitude Induced Thromboembolic Disorder: Role of Endogenous miRNA Sponge

Background: The pathophysiology of Deep vein thrombosis (DVT) is considered as multifactorial, where thrombus formation is interplay of genetic and acquired risk factors. Lately, different pipelines have been developed to identify novel lncRNAs in different diseases, however a little is known about the expression profile and roles of lncRNAs in human subjects developing DVT at high altitude. Methods: In the present study, using RNA sequencing, we compared peripheral blood lncRNA expression profile in human High Altitude deep Vein Thrombosis (HA-DVT) patients with high altitude control and sea level control human subjects. We used DESeq to identify differentially expressed (DE) genes. We identified the noncoding RNAs by annotation database that includes lncRNAs from the NONCODE 3.0 human noncoding RNA database. This was followed by the functional characterization of the identified DE lncRNAs by Co-expressed protein-coding genes analysis. We further performed in silico putative lncRNA-miRNA association study to unravel the endogenous miRNA sponge associated with our candidate lncRNAs. Finally, to validate the in silico findings, siRNA knockdown assay of the candidate LncRNAs was conducted in primary endothelial cells Results: We identified 973 differentially expressed lncRNAs. Co-expressed protein-coding genes analysis resulted in a list of 722 coexpressed protein-coding genes with a Pearson correlation coefficients &gt;0.7. The functional annotation of co-expressed genes and putative proteins revealed their involvement in the hypoxia, immune response and coagulation cascade. Putative lncRNA-miRNA association analysis revealed several miRNAs associated with cardiovascular disorders. Through its miRNA response elements (MREs) to compete for miR-143 and miR-15, lncRNA-LINC00659 and UXT-AS1 regulates the expression of prothrombotic genes. Furthermore, in vitro RNA interference (siRNA) simultaneously suppressed lncRNAs and target gene mRNA level. Conclusions: This transcriptome profile describes several potential mechanisms of interaction between lncRNAs, the coding genes, miRNAs and regulatory transcription factors that define the thrombotic signature and may be used in establishing lncRNAs as biomarker in HA-DVT.

Effects of notoginseng and ginkgo leaf tablets on cardiac function and serum inflammatory factors in hypoxia deacclimatized rats and its mechanism

To study the effects of notoginseng, gingko leaf and rhodiola on cardiac functions and the serum inflammatory factors interleukin-6,interleukin-10, and TNF-α of rats with hypoxia deacclimatization, to explore the mechanism of hypoxia detoxification. Forty SD rats were randomly divided into notoginseng group(n=10), gingko leaf group(n=10), rhodiola group(n=10) and high altitude control group(n=10) after fed in a hypobaric hypoxia chamber(simulated altitude of 5 000 m) for 3 month, while 10 rats fed at normal pressure and oxygen environment for 3 month were used as the plain control group. Rats in notoginseng group, gingko leaf group and rhodiola group were treated with notoginseng, gingko leaf tablets or rhodiola suspension through intragastric administration (200 mg/kg,twice a day, for 10 days). After the rats got intraperitoneal anesthesia with 10% urethane, 5 min pulmonary artery pressure curve were traced continuously while pulmonary artery pressure (PAP). Left and right ventricular systolic pressure (VSP) and ventricular diastolic pressure (VEDP), the hemodynamic parameters were detected through a multi-channel physiological recorder. Serum tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), superoxide dismutase (SOD) and malondialdehyde (MDA) were measured. Right ventricular systolic pressure (RVSP), right ventricular end-diastolic pressure (RVEDP), mean pulmonary artery pressure (mPAP), left vent-ricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP),IL-6,and IL-10 were higher in notoginseng group, gingko leafgroup, rhodiola group and high altitude control group than those in plain control group(P＜0.05 or P＜0.01). The contents of MDA and TNF-α were higher while the level of SOD was lower in rhodiola group and high altitude control group than those in plain control group(P＜0.01). The contents of MDA and TNF-α were lower while the level of SOD was higher in notoginseng group, gingko leaf group and rhodiola group than those in high altitude control group(P＜0.01). The levels of RV,RVHI,RVSP,RVEDP,LVSP,LVEDP,IL-10 and TNF-α were statistically changed in notoginseng group than those in gingko leaf group and rhodiola group(P＜0.05orP＜0.01). Notoginseng, gingkoleaf and rhodiola can enhance antioxidant capacity of body and improve ventricular functions and Notoginseng, gingko leaf and rhodiola can effectively enhance the functions of ventricular and hypoxia tolerance and inhibit the expressions of inflammatory factors in rats during the hypoxia deacclimatization.

Solnatide Demonstrates Profound Therapeutic Activity in a Rat Model of Pulmonary Edema Induced by Acute Hypobaric Hypoxia and Exercise

The synthetic peptide solnatide is a novel pharmacologic agent that reduces extravascular lung water, blunts reactive oxygen species production, and improves lung function due to its ability to directly activate the epithelial sodium channel. The goal of this study was to investigate the effect of solnatide in pulmonary edema induced by acute hypobaric hypoxia and exercise in rats, which is considered a model for high-altitude pulmonary edema. Sprague-Dawley rats were assigned to low-altitude control and eight treatment groups. Animals of all groups were subjected to exhaustive exercise in a hypobaric hypoxic environment simulating an altitude of 4,500 meters, followed by simulated ascent to 6,000 meters. After 48h at 6,000 meters, rats were given sodium chloride, dexamethasone, aminophylline, p38 mitogen activated protein kinase inhibitor, and NOD-like receptor containing a pyrin domain 3 inhibitor, or one of three different doses of solnatide, once daily for 3 consecutive days. After 3days, arterial blood gas, BAL fluid, lung water content, and histologic and ultra-microstructure analyses were performed. Tight junction protein occludin was assayed by using immunohistochemistry. Rats treated with solnatide had significantly lower BAL fluid protein and lung water content than high-altitude control rats. Lungs of solnatide-treated rats were intact and showed less hemorrhage and disruption of the alveolar-capillary barrier than those of high-altitude control animals. Occludin expression was significantly higher in solnatide-treated animals, compared with high-altitude control, dexamethasone-, and aminophylline-treated animals. Solnatide reduced pulmonary edema, increased occludin expression, and improved gas-blood barrier function during acute hypobaric hypoxia and exercise in rats. These results provide a rationale for the clinical application of solnatide to patients with pulmonary edema and exposure to a high-altitude hypoxic environment.

Small interfering RNA (siRNA) targeting vascular endothelial growth factor inhibits vascular leakage in brain of rats exposed to high altitude

To observe the change of expression of vascular endothelial growth factor (VEGF) and vascular leakage in the brain of rats exposed to high altitude with siRNA targeting vascular endothelial growth factor and explore the pathological mechanism and preventive approach of high altitude cerebral edema (HACE). Fifty male Wistar rats were divided randomly into normal control group (Ncon), high altitude control group (Hcon), intraventricular normal saline control group (Scon), intraventricular siRNA group (CVI) and intravenous siRNA group (IVI). Rats in Ncon were raised normally. Rats in Hcon, Scon, CVI and IVI pretreated with intravenous injection of normal saline, intraventricular injection of normal saline, intraventricular injection of siRNA and intravenous injection of siRNA respectively were exposed to a low-pressure cabin mimicking a high altitude of 7000 m for 24 h. The ratio of dry and wet brain weight was calculated and the sodium fluorescein leakage calculated to evaluate the cerebral edema and the blood brain barrier permeability. Also the real-time quantitative RT-PCR was employed to detect the expression of VEGF mRNA and the Western blot the expression of VEGF. Compared with rats in NC, high altitude exposure led to a significant increase in the levels of VEGF mRNA (from 21.6 + or - 3.5 K copies/microg to 36.3 + or - 3.9 K copies/microg, P < 0.01) and protein (from 48 + or - 0.09 to 0.77 + or - 0.12, P < 0.01) in rat brain and fluorescence intensity of sodium fluorescein increased significantly (from 548 + or - 48 rfu/mg to 674 + or - 32 rfu/mg, P < 0.01). Intravenous injection of siRNA targeting to VEGF caused no significant change of expression VEGF mRNA and protein and fluorescence intensity of sodium fluorescein in rat brain (P > 0.05, respectively). While compared with rats in HC, intraventricular injection of siRNA targeting to VEGF caused the significant reduction of expression of VEGF mRNA (from 36.3 + or - 3.9 to 19.9 + or - 4.3, P < 0.01) and protein (from 0.77 + or - 0.12 to 0.44 + or - 0.13, P < 0.01) and fluorescence intensity of sodium fluorescein (from 674 + or - 32 rfu/mg to 542 + or - 77 rfu/mg, P < 0.05) in rat brain. There were no significant change in the ratio of dry and wet brain weight among five groups. VEGF may play a key role in the pathologic process of HACE. Intraventricular injection of siRNA targeting to VEGF inhibits the expression of VEGF and prevent the high altitude-induced vascular leakage. These findings might provide a basis for new preventive approaches of cerebral edema.

Splenic Syndrome: A Rare Indication for Splenectomy

Splenic infarction due to sickle cell trait and high-altitude stress has been reported in the literature. Contributing factors leading to infarction are degree of altitude stress and status of physical condition. Medical therapy, which consists of evacuation from high altitude, intravenous fluids, supplemental oxygen, and pain control, has been the mainstay of treatment. However, some patients require surgical intervention. We describe six patients with sickle cell trait who sustained splenic infarctions due to high-altitude stress; two of these patients required splenectomy for near-total splenic necrosis and intractable pain. A review of the literature demonstrates that the common indications for splenectomy are splenic rupture, extensive splenic necrosis, or persistent abdominal pain.

Hypersonic flight experience

The flight test results from the X-15, Asset, Prime, Reentry F and Shuttle Orbiter flight research programmes are reviewed and compared with theory and ground- based experiments. Primary emphasis is placed on our present capability to predict aerodynamic coefficients and stability derivatives, and distributions of surface pressure and aerodynamic heating rate for typical orbital and sub-orbital hypersonic vehicles. Overall, this comparison demonstrates the feasibility of designing hypersonic vehicles based on tests in conventional perfect-gas wind tunnels supplemented by state-of-the-art CFD analysis. At Mach numbers up to approximately 8, real-gas effects are small and Mach number/Reynolds number simulation is sufficient to insure accurate prediction of aerodynamic characteristics. At higher mach numbers, real-gas effects become important but appear to affect primarily pitching moment and to have little influence on other aerodynamic characteristics. Viscous interaction effects appear to be well correlated by the viscous interaction parameter V̄' ∞ , and to affect primarily axial force. With the exception of RCS jet interactions, stability and control derivatives are well predicted throughout the hypersonic flight régime. State-of-the-art aerodynamic heating techniques appear to give accurate predictions for laminar and fully turbulent attached flows so long as there are no strong shock interactions or non-equilibrium chemistry effects. For such flows, heating rate distributions depend only weakly on Mach number for M ∞ ≥ 8 and hence M ∞ ≈ 8-10 wind tunnel results can be used throughout the hypersonic speed range. For high- speed, high-altitude flight, surface catalycity effects can have a major influence on heating rates but modern, finite-rate boundary layer analyses are capable of predicting major trends. The major remaining challenges are the accurate prediction of: (1) real-gas effects on longitudinal trim, (2) the effectiveness of blended high altitude control systems, (3) shock interaction heating, (4) heating rates for separated vortex-dominated leeside flows, and (5) boundary layer transition and relaminarzation. Finally, it is pointed out that there are no flight data on the propulsion-airframe integration effects that are so important for airbreathing launch vehicles.

Pulmonary vascular disease in a rabbit a high altitude

A male weanling rabbit of the New Zealand White strain, born and living at an altitude of 3800 m in La Paz, Bolivia, developed right ventricular hypertrophy. This was found to be associated with growth of vascular smooth muscle cells in the intima of pulmonary arterioles, and contrasted with muscularization of the walls of pulmonary arterioles, without extension into the intima, found in a healthy, high-altitude control rabbit of the same strain. A low-altitude control showed no such muscularization. It is concluded that alveolar hypoxia, acting directly or through an intermediate agent, is a growth factor for vascular smooth muscle cells in pulmonary arterioles. This is the first report of pulmonary vascular disease due to high altitude in rabbits.

Excessive polycythemia of high altitude: role of ventilatory drive and lung disease.

Persons residing at high altitude who develop excessive polycythemia are more hypoxemic than normal high-altitude residents. We investigated the causes of hypoxemia in 20 patients with excessive polycythemia residing at an altitude of 3,100 m. Lung disease evidenced by abnormal spirometric features and results of a respiratory questionnaire was present in 10 of 20 patients and resulted in increased alveolar-arterial difference for PO2 [(A-a)PO2]. The excessive hypoxemia in the patients with normal lungs was not due to increased (A-a)PO2. We measured ventilatory responses to hypoxia and to hypercapnia to determine whether blunting of these responses was a cause of this excessive hypoxemia. We found, however, that chemical drives to breathe, although blunted, were the same in patients with polycythemia as in high-altitude control subjects. However, an abnormal breathing pattern was observed; the polycythemic patients had a smaller tidal volume and a greater ratio of dead space to tidal volume than did the normal subjects. In addition, the polycythemic patients had increased minute ventilation on breathing 100 percent O2, whereas the normal subjects did not. Thus, hypoxic depression of ventilation may have been present. Our findings suggested that blunted chemical drives are not causative in this disease, and that some other cause of hypoxemia must be present.

Subtle Surface Mapping--Kelsh Plotter Techniques: ABSTRACT

Studies indicate that the Kelsh stereoplotter is capable of locating subtle surface anomalies using high-altitude photos and ground control. Petroleum explorationists in the early 1950s used the Kelsh plotter to map in detail known geologic surface structures in order to determine the amount of structural closure and fault throws. In the early 1960s, with the advent of high-altitude photographic coverage over much of the United States, a new role developed for the plotter. The large, 40-sq-mi/print, lateral stereoscopic coverage allows a much wider look at large areas, and thus a new system of geologic reconnaissance mapping with extremely accurate results. Tip and tilt, inherent in all aerial photographs, can be removed. An enlargement factor of 5, together with vertical ground controls for each stereo pair, makes possible dip-magnitude readings of 1/2 degree and accurate structural elevation work. Using the Kelsh plotter to evaluate larger geologic provinces, many previously undiscovered subtle nosings, faulted noses, and independent surface closures become apparent. Cross-section work and measurement of the thickness of formations also may be accomplished. A newly developed system of polarized light makes possible the use of color aerial photographs with the same accuracy as conventional black and white prints. End_of_Article - Last_Page 767------------