LncRNA and Protein Expression Profiles Reveal Heart Adaptation to High-Altitude Hypoxia in Tibetan Sheep.

The Tibetan sheep has an intricate mechanism of adaptation to low oxygen levels, which is influenced by both genetic and environmental factors. The heart plays a crucial role in the adaptation of Tibetan sheep to hypoxia. In the present study, we utilized transcriptomic and proteomic technologies to comprehensively analyze and identify the long non-coding RNAs (lncRNAs), genes, proteins, pathways, and gene ontology (GO) terms associated with hypoxic adaptation in Tibetan sheep at three different altitudes (2500 m, 3500 m, and 4500 m). By integrating the differentially expressed (DE) lncRNA target genes, differentially expressed proteins (DEPs), and differentially expressed genes (DEGs), we were able to identify and characterize the mechanisms underlying hypoxic adaptation in Tibetan sheep. Through this integration, we identified 41 shared genes/proteins, and functional enrichment analyses revealed their close association with lipid metabolism, glycolysis/gluconeogenesis, and angiogenesis. Additionally, significant enrichment was observed in important pathways such as the PPAR signaling pathway, glycolysis/gluconeogenesis, the oxoacid metabolic process, and angiogenesis. Furthermore, the co-expression network of lncRNAs and mRNAs demonstrated that lncRNAs (MSTRG.4748.1, ENSOART00020025894, and ENSOART00020036371) may play a pivotal role in the adaptation of Tibetan sheep to the hypoxic conditions of the plateau. In conclusion, this study expands the existing database of lncRNAs and proteins in Tibetan sheep, and these findings may serve as a reference for the prevention of altitude sickness in humans.

Yak milk-derived exosomal microRNAs regulate intestinal epithelial cells on proliferation in hypoxic environment.

Intestinal epithelial cells (IEC) act as an important intestinal barrier whose function can be impaired upon induction by hypoxia. Although intestinal barrier injuries are preventable by milk-derived exosomal microRNAs (miRNAs), the underlying mechanism remains poorly understood. This study aimed to characterize the effect of yak and cow milk-derived exosomal miRNA on the barrier function of IEC-6 under hypoxic conditions, and explore the mechanism of yak milk exosomal miRNA to relieve the hypoxia stress. First, by Illumina HiSeq 2500 (Illumina Inc., San Diego, CA) sequencing, the miRNA expression was systematically screened, and differential expression of 130 miRNAs was identified with 51 being upregulated and 79 downregulated in yak and cow milk-derived exosomes. Furthermore, the top 20 miRNAs that had a relatively consistent high expression in yak milk exosome were identified, and bta-miR-34a was found to be an effective regulator for alleviating hypoxic injury of IEC-6. In vitro assay of the role of bta-miR-34a on survival of IEC-6 in hypoxia by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) confirmed its effectiveness to significantly increase IEC-6 survival up to 13% for 12 h, and up to 9.5% for 24 h. Investigation on the regulatory relationship between bta-miRNA-34a and the hypoxia-inducible factor/apoptosis signaling pathway provided insights into the possible mechanisms by which bta-miR-34a activated the hypoxia-inducible factor and apoptosis signaling pathway, thus promoting IEC-6 survival. The results of this study suggest an important relationship between miRNA expression and intestine barrier integrity, which facilitated further understanding of the physiological function of yak and cow milk exosomal miRNAs, as well as mechanisms of hypoxia-driven epithelial homeostasis.

Identifying Candidate Genes for Hypoxia Adaptation of Tibet Chicken Embryos by Selection Signature Analyses and RNA Sequencing.

The Tibet chicken (Gallus gallus) lives on the Qinghai-Tibet Plateau and adapts to the hypoxic environment very well. The objectives of this study was to obtain candidate genes associated with hypoxia adaptation in the Tibet chicken embryos. In the present study, we used the fixation index (Fst) and cross population extended haplotype homozygosity (XPEHH) statistical methods to detect signatures of positive selection of the Tibet chicken, and analyzed the RNA sequencing data from the embryonic liver and heart with HISAT, StringTie and Ballgown for differentially expressed genes between the Tibet chicken and White leghorn (Gallus gallus, a kind of lowland chicken) embryos hatched under hypoxia condition. Genes which were screened out by both selection signature analysis and RNA sequencing analysis could be regarded as candidate genes for hypoxia adaptation of chicken embryos. We screened out 1772 genes by XPEHH and 601 genes by Fst, and obtained 384 and 353 differentially expressed genes in embryonic liver and heart, respectively. Among these genes, 89 genes were considered as candidate genes for hypoxia adaptation in chicken embryos. ARNT, AHR, GSTK1 and FGFR1 could be considered the most important candidate genes. Our findings provide references to elucidate the molecular mechanism of hypoxia adaptation in Tibet chicken embryos.

Integrative plasma proteomic and microRNA analysis of Jersey cattle in response to high-altitude hypoxia.

Blood has been widely collected and analyzed for diagnosing and monitoring diseases in humans and animals; a range of plasma proteins and peptide can be used as biomarkers to describe pathological or physiological status. Changes in the environment such as high-altitude hypoxia (HAH) can lead to adaptive changes in the blood system of mammals. However, the adaptation mechanism induced by HAH remains unclear. In this study, we used 12 multiparous Jersey cattle (400 ± 35 kg, average 3 yr old, dry period). We applied an iTRAQ (isobaric tags for relative and absolute quantitation) proteomics approach and microRNA (miRNA) microarray to explore differences in the plasma proteomic and miRNA profiles of Jersey cattle exposed to HAH conditions in Nyingchi, Tibet (altitude 3,000 m) and HAH-free conditions in Shenyang, China (altitude 50 m). Such quantitative proteomic strategies are suitable for accurate and comprehensive prediction of miRNA targets. In total, 264 differentially expressed proteins (127 upregulated, fold-change >1.2; 137 downregulated, fold-change <0.8) and 47 differential miRNAs (25 upregulated, fold-change >2; 22 downregulated, fold-change <0.5) were observed in the HAH-stressed group compared with the HAH-free group. Integrative analysis of proteomic and miRNA profiles demonstrated that the biological processes associated with differentially expressed proteins were immune response, complement system, and conjugation system. Integrative analysis of canonical pathways showed that most were associated with acute phase response signaling (z-score = -0.125), liver X receptor/retinoid X receptor (LXR/RXR) activation pathway (z-score = 1.134), coagulation system (z-score = -0.943), and complement system (z-score = -0.632). The current results indicated that Jersey cattle exposed to HAH could adapt to that condition through regulation of inflammatory homeostasis by inhibiting the acute phase response, coagulation system, and complement system and promoting LXR/RXR activation.

Expression of OPA1 and Mic60 genes and their association with mitochondrial cristae morphology in Tibetan sheep.

In order to investigate the relationship between the expression of OPA1 and Mic60 genes and the shape of mitochondrial cristae and to explore the mechanism of Tibetan sheep adapting to a high altitude hypoxia environment, we investigate respiratory rate, mitochondrial cristae and the expression of OPA1 and Mic60 in four different tissues (myocardial, skeletal muscle, spleen and kidney) in Tibetan sheep and Small Tail Han sheep. Tibetan sheep had a higher respiratory rate than Small Tail Han sheep (p < 0.01). In the same tissue, the expression of OPA1 and Mic60 was higher (p < 0.05) in Tibetan sheep than Small Tail Han sheep. Between tissues, the expression of OPA1 and Mic60 was found to be lower (p < 0.05) in spleen than the other three tissues in both breeds. Mitochondrial cristae was dense and clear in myocardial and skeletal muscle but was relatively sparse and slightly swollen in kidney. In spleen, cristae was least and swollen and the gap between the cristae was large. The width of the mitochondrial cristae in the spleen was significantly larger than the width between the inner and outer membranes; however, it had little difference in the other three tissues. The width of mitochondrial cristae was significantly larger in the spleen than that in other tissues (p < 0.05). The numbers of mitochondrial cristae in the four tissues of Tibetan sheep were larger than those in Small Tail Han sheep (p < 0.05). The unique characters of the mitochondrial cristae in Tibetan sheep may be related to its adaption to a high altitude hypoxia environment.

Overexpression of genes associated with hypoxia in cattle adapted to Trans Himalayan region of Ladakh.

Ladakh is an important part of the Trans-Himalayan region located between the Kunlun mountain range in the north and the main Great Himalayas to the south in the state of Jammu and Kashmir of India. The local cattle from Leh and Ladakh region, known as "Ladakhi cattle" is a unique germplasm having an excellent adaptation potential to high altitude hypobaric stress. In the present study, an effort was made to evaluate the transcriptional pattern of hypoxia inducing factor-1 (HIF-1) and several of its regulated genes in PBMCs of local Ladakhi cattle, Holstein Frisian crosses, Jersey (exotic) maintained at high altitude region and Sahiwal (Bos indicus) and Karan Fries (cross bred) cattle maintained in tropical environment. The combined data set indicated increased expression of HIF-1 and its regulated genes viz., glucose transporter 1 (GLUT1), vascular endothelial growth factor (VEGF), and hexokinase (HK2) in high altitude cattle indicating their importance in maintaining cellular homeostasis during high altitude hypoxia. The data indicated that hypoxia associated genes accumulated under hypoxic conditions are part of an essential adaptive component for adaptation to the high altitude of the trans-Himalayan region. In contrary, higher expression of molecular chaperons' viz., HSP70 and HSP90 in tropically adapted cattle give tolerance to high ambient temperature prevalent in tropical condition. In conclusion, HIF-1 and its regulatory genes could be termed as important candidates for producing homeostatic responses to hypoxia in cattle populations reared in higher altitudes of the Trans-Himalayan region.

Polymorphisms in the Egl nine homolog 3 (EGLN3) and Peroxisome proliferator activated receptor-alpha (PPARα) genes and their correlation with hypoxia adaptation in Tibetan chickens.

Peroxisome proliferator activated receptor-alpha (PPARα) and Egl nine homolog 3 (EGLN3) play critical roles in facilitating the adaptation to a hypoxic environment. However, the relationship between EGLN3 and PPARα variants and hypoxic adaptation remains poorly understood in Tibetan chickens. To better understand the effects of genetic variation, we sequenced exons of PPARα and EGLN3 in 138 Lowland chickens (LC) from 7 breeds that were located in Emei, Miyi, Shimian, Wanyuan, Pengxian, and Muchuan in the Sichuan province, and Wenchang in the Hainan province (altitudes for these locations are below 1800 meters). Total 166 Tibetan chickens (TC) from 7 subpopulations that were located in Shigatse, Lhoka, Lhasa, Garze, Aba, Diqing and Yushu in the Tibetan area were also sequenced (altitudes greater than 2700 meters). One single-nucleotide polymorphism (rs316017491, C > T) was identified in EGLN3 and was shared by TC and LC with no significant difference for allele frequencies between them (P > 0.05). Six single-nucleotide polymorphisms (SNP1, A29410G; SNP2, rs13886097; SNP3, T29467C; SNP4, rs735915170; SNP5, rs736599044; and SNP6, rs740077421) including one non-synonymous mutation (SNP2, T > C) were identified in PPARα. This is the first report of SNP1 and SNP3. There was a difference between TC and LC for allele frequencies (P <0.01), except for SNP1, SNP4, and SNP5) The fix index statistic test indicated that there was population differentiation between TC and LC for SNP2, SNP3, and SNP6 in PPARα (P < 0.05). Phylogenetic analysis showed that the genetic distance among chickens, finch and great tit were close for both EGLN3 and PPARα. Bioinformatics analysis of PPARα showed that SNP2 leads to an amino acid substitution of Ile for Met, which results in the protein being more likely to be hydrolyzed. Thus, genetic variation in PPARα may play a role in the ability of TC to adapt to a high altitude environment; however we were unable to identify a relationship between polymorphisms in EGLN3 and environmental adaptability.

High altitude hypoxia as a factor that promotes tibial growth plate development in broiler chickens.

Tibial dyschondroplasia (TD) is one of the most common problems in the poultry industry and leads to lameness by affecting the proximal growth plate of the tibia. However, due to the unique environmental and geographical conditions of Tibet, no case of TD has been reported in Tibetan chickens (TBCs). The present study was designed to investigate the effect of high altitude hypoxia on blood parameters and tibial growth plate development in chickens using the complete blood count, morphology, and histological examination. The results of this study showed an undesirable impact on the overall performance, body weight, and mortality of Arbor Acres chickens (AACs) exposed to a high altitude hypoxic environment. However, AACs raised under hypoxic conditions showed an elevated number of red blood cells (RBCs) and an increase in hemoglobin and hematocrit values on day 14 compared to the hypobaric normoxia group. Notably, the morphology and histology analyses showed that the size of tibial growth plates in AACs was enlarged and that the blood vessel density was also higher after exposure to the hypoxic environment for 14 days, while no such change was observed in TBCs. Altogether, our results revealed that the hypoxic environment has a potentially new role in increasing the blood vessel density of proximal tibial growth plates to strengthen and enhance the size of the growth plates, which may provide new insights for the therapeutic manipulation of hypoxia in poultry TD.

A non-synonymous SNP with the allele frequency correlated with the altitude may contribute to the hypoxia adaptation of Tibetan chicken.

The hypoxia adaptation to high altitudes is of considerable interest in the biological sciences. As a breed with adaptability to highland environments, the Tibetan chicken (Gallus gallus domestics), provides a biological model to search for genetic differences between high and lowland chickens. To address mechanisms of hypoxia adaptability at high altitudes for the Tibetan chicken, we focused on the Endothelial PAS domain protein 1 (EPAS1), a key regulatory factor in hypoxia responses. Detected were polymorphisms of EPAS1 exons in 157 Tibetan chickens from 8 populations and 139 lowland chickens from 7 breeds. We then designed 15 pairs of primers to amplify exon sequences by Sanger sequencing methods. Six single nucleotide polymorphisms (SNPs) were detected, including 2 missense mutations (SNP3 rs316126786 and SNP5 rs740389732) and 4 synonymous mutations (SNP1 rs315040213, SNP4 rs739281102, SNP6 rs739010166, and SNP2 rs14330062). There were negative correlations between altitude and mutant allele frequencies for both SNP6 (rs739010166, r = 0.758, p<0.001) and SNP3 (rs316126786, r = 0.844, P<0.001). We also aligned the EPAS1 protein with ortholog proteins from diverse vertebrates and focused that SNP3 (Y333C) was a conserved site among species. Also, SNP3 (Y333C) occurred in a well-defined protein domain Per-AhR-Arnt-Sim (PAS domain). These results imply that SNP3 (Y333C) is the most likely casual mutation for the high-altitude adaption in Tibetan chicken. These variations of EPAS1 provide new insights into the gene's function.

PULMONARY ARTERIAL DISEASE ASSOCIATED WITH RIGHT-SIDED CARDIAC HYPERTROPHY AND CONGESTIVE HEART FAILURE IN ZOO MAMMALS HOUSED AT 2,100 M ABOVE SEA LEVEL.

Subacute and chronic mountain sickness of humans and the related brisket disease of cattle are characterized by right-sided congestive heart failure in individuals living at high altitudes as a result of sustained hypoxic pulmonary hypertension. Adaptations to high altitude and disease resistance vary among species, breeds, and individuals. The authors conducted a retrospective survey of right-sided cardiac hypertrophy associated with pulmonary arterial hypertrophy or arteriosclerosis in zoo mammals housed at Africam Safari (Puebla, México), which is located at 2,100 m above sea level. Seventeen animals with detailed pathology records matched the study criterion. Included were 10 maras (Dolichotis patagonum), 2 cotton-top tamarins (Saguinus oedipus oedipus), 2 capybaras (Hydrochaeris hydrochaeris), and 1 case each of Bennet's wallaby (Macropus rufogriseus), nilgai antelope (Boselaphus tragocamelus), and scimitar-horned oryx (Oryx dammah). All had right-sided cardiac hypertrophy and a variety of arterial lesions restricted to the pulmonary circulation and causing arterial thickening with narrowing of the arterial lumen. Arterial lesions most often consisted of medial hypertrophy or hyperplasia of small and medium-sized pulmonary arteries. All maras also had single or multiple elevated plaques in the pulmonary arterial trunk consisting of fibrosis, accompanied by chondroid metaplasia in some cases. Both antelopes were juvenile and died with right-sided congestive heart failure associated with severe pulmonary arterial lesions. To the authors' knowledge, this is the first description of cardiac and pulmonary arterial disease in zoo mammals housed at high altitudes.

Increased prevalence of EPAS1 variant in cattle with high-altitude pulmonary hypertension.

High-altitude pulmonary hypertension (HAPH) has heritable features and is a major cause of death in cattle in the Rocky Mountains, USA. Although multiple genes are likely involved in the genesis of HAPH, to date no major gene variant has been identified. Using whole-exome sequencing, we report the high association of an EPAS1 (HIF2α) double variant in the oxygen degradation domain of EPAS1 in Angus cattle with HAPH, mean pulmonary artery pressure >50 mm Hg in two independent herds. Expression analysis shows upregulation of 26 of 27 HIF2α target genes in EPAS1 carriers with HAPH. Of interest, this variant appears to be prevalent in lowland cattle, in which 41% of a herd of 32 are carriers, but the variant may only have a phenotype when the animal is hypoxemic at altitude. The EPAS1 variant will be a tool to determine the cells and signalling pathways leading to HAPH.

Pulmonary arterial pressure testing for high mountain disease in cattle.

High mountain or brisket disease is an economically costly disease of cattle raised at elevations greater than 1500 m (5000 ft). It appears that no one breed is resistant to the effects of high-altitude hypoxia. Some breeds, and pedigrees within breeds, appear to be more naturally resistant to the effects of high altitude. Multiple factors contribute to the variance in pulmonary arterial pressure in cattle, including breed, gender, body condition, concurrent illness, environmental conditions, elevation, and genetics. Pulmonary arterial pressure testing is an effective diagnostic and management tool used to identify clinically affected and high-risk animals. The procedure can be performed in the field and is an economically valuable method for the selection and breeding management of beef cattle raised at high altitude.

The heart and pulmonary circulation at high altitudes: healthy highlanders and chronic mountain sickness.

More than 140 million people worldwide live >2500 m above sea level. Of them, 80 million live in Asia, and 35 million live in the Andean mountains. This latter region has its major population density living above 3500 m. The primary objective of the present study is to review the physiology, pathology, pathogenesis, and clinical features of the heart and pulmonary circulation in healthy highlanders and patients with chronic mountain sickness. A systematic review of worldwide literature was undertaken, beginning with the pioneering work done in the Andes several decades ago. Original articles were analyzed in most cases and English abstracts or translations of articles written in Chinese were reviewed. Pulmonary hypertension in healthy highlanders is related to a delayed postnatal remodeling of the distal pulmonary arterial branches. The magnitude of pulmonary hypertension increases with the altitude level and the degree of exercise. There is reversal of pulmonary hypertension after prolonged residence at sea level. Chronic mountain sickness develops when the capacity for altitude adaptation is lost. These patients have moderate to severe pulmonary hypertension with accentuated hypoxemia and exaggerated polycythemia. The clinical picture of chronic mountain sickness differs from subacute mountain sickness and resembles other chronic altitude diseases described in China and Kyrgyzstan. The heart and pulmonary circulation in healthy highlanders have distinct features in comparison with residents at sea level. Chronic mountain sickness is a public health problem in the Andean mountains and other mountainous regions around the world. Therefore, dissemination of preventive and therapeutic measures is essential.

Examination of potential methods to predict pulmonary arterial pressure score in yearling beef cattle.

Susceptibility of beef cattle to high altitude disease (HAD) is of major importance to economic and genetic selection on high elevation ranches. However, currently the best indicator of HAD susceptibility is the pulmonary arterial pressure (PAP) test, a test with high cost and invasive nature. Therefore, 2 experiments were undertaken to determine whether emerging technologies that predict blood components could be used to predict the PAP score in yearling Angus cattle. In Exp. 1, 39 yearling Angus bulls were used to determine if a relationship existed between PAP score and 10 blood components provided by a hemogram using whole blood or oxygen saturation as predicted by pulse oximetry in nonanesthetized cattle measured rectally or orally. Three of the hemogram values (packed cell volume, hemoglobin concentration, and red cell distribution width) were correlated (P < 0.10) with the PAP score. Prediction equations for PAP score were generated using the hemogram values and resulted in R2 values of 0.375 and 0.305 for the regression model using all of values and the best 2-variable model, respectively. Pulse oximetry was able to provide oxygen saturation predictions rectally or orally; however, the predicted values were not correlated with the PAP score (P > 0.10) or with each other (P > 0.10). In Exp. 2, 84 yearling Angus cattle (62 bulls, 22 heifers) were used to evaluate the ability of a portable clinical analyzer to predict the PAP score using 11 blood components from a sample of whole blood evaluated at the processing chute. The portable clinical analyzer was able to provide values for all of the 11 blood components; however, none of the predicted values were correlated with the PAP score (P > 0.10). In these preliminary experiments, 3 blood component values provided via the hemogram were the only variables both correlated with the PAP score and able to contribute to the development of a useful PAP prediction equation that could reduce the cost of traditional measures of HAD susceptibility. Future research is needed to determine whether additional blood components or emerging blood analysis technologies are able to accurately predict the PAP score in beef cattle.

Comparative physiology of hypoxic pulmonary hypertension: historical clues from brisket disease.

Some of the most valuable contributions to science have come about serendipitously, and, in 1913, when George Glover and Issac Newsom were commissioned by Colorado cattle ranchers to study high mountain disease, there was no way to anticipate the tremendous impact they would have on the study of high-altitude cardiopulmonary physiology. It was through the study of this agricultural malady that the correlation between chronic hypoxia, pulmonary hypertension, medial hypertrophy of the small pulmonary arteries, and right ventricular (RV) hypertrophy was recognized. The amount of vascular smooth muscle comprising the medial layer of pulmonary arteries varies significantly across species and can be used to predict the magnitude of pulmonary hypertension and RV hypertrophy elicited in response to chronic hypoxia. Within species, age and gender both significantly influence the severity of chronic hypoxic pulmonary hypertension and RV hypertrophy. However, despite all that we now know about hypoxic pulmonary hypertension, the specific mechanism(s) that differentiate the hypo- from the hyperresponder have yet to be elucidated. Adventitial fibroblast differentiation, circulating vascular progenitor cells, the presence or absence of specific vascular smooth muscle phenotypes, the upregulation or downregulation of vasoactive mediators, splice variants of oxygen-sensitive transcription factors, upregulation of growth factors, Ca(2+) sensitization, and/or the Rho/Rho-kinases signaling cascade could all potentially play a role in determining the extent of the vascular response to hypoxia within a species. Understanding the mechanisms that determine why some people, as well as some animals, exhibit a marked susceptibility to hypoxia is an important endeavor with far-reaching implications.

Echocardiographic changes induced by moderate to marked hypobaric hypoxia in dogs.

Hypobaric (high-altitude) hypoxia is a physiologic cause of pulmonary hypertension, and alters left ventricular (LV) systolic and diastolic function. In the presence of tricuspid regurgitation, systolic pulmonary artery pressure can be measured noninvasively using the peak tricuspid regurgitation velocity and the Bernoulli equation. In the absence of measurable tricuspid regurgitation, severity of pulmonary hypertension may be estimated using two-dimensional, M-mode, and Doppler-derived parameters. To evaluate the usefulness of echocardiographic parameters for detecting mild-to-moderate pulmonary hypertension caused by moderate-to-marked hypoxia and to study the effect of high-altitude hypoxia on systolic and diastolic LV function in dogs, 19 Greenland dogs were examined at moderate altitude (2300 m) and high altitude (3500 m), and 10 Greenland control dogs were examined at 700-900 m. Evaluated parameters were pulmonary flow profile (shape, right ventricular acceleration time (RVAT), ejection time (RVET), RVAT/ET), peak mitral inflow velocities (LVE, LVA, LVE/A-ratio), LV % fractional shortening (FS), systolic time intervals (LVPEP, LVPEP/ET), and stroke volume index (SVI). Notching during deceleration was common in dogs at high altitude and in the control dogs, but not in dogs at moderate altitude. RVAT was shorter in dogs at high altitude compared with moderate altitude, but not compared with control dogs. Peak A-velocity was higher and E/A-ratio was lower in dogs at high altitude compared with moderate altitude and control dogs. FS was increased in dogs at high altitude compared with moderate altitude, and LVPEP and LVPEP/ET were shorter in the dogs at high altitude compared with moderate altitude and control dogs. In conclusion, significant differences in pulmonary flow profiles and systolic and diastolic parameters can be observed echocardiographically in dogs at different degrees of hypobaric hypoxia. However, overlap between the groups compromises their usefulness for diagnosing and estimating the degree of mild-to-moderate pulmonary hypertension in individual dogs.

Wheel-well and cargo compartment temperatures of large aircraft in flight: implications for stowaways.

BACKGROUND: Desperate people sometimes risk journeys as stowaways in aircraft wheel-wells. Some of them survive, despite the risks of being crushed by retracting landing gear, falling when the gear deploys for landing, or experiencing severe hypoxia and hypobaria in-flight. This study evaluates the level of hypothermia to which stowaways in aircraft may be exposed. METHODS: Miniature dataloggers were used to record in-flight temperatures in aircraft wheel-wells and cargo compartments. Temperatures were measured for front and side wheel-wells (FW and SW, respectively) on 36 flights by C-130 aircraft (mean duration 3.3 h, mean cruise altitude 5588 m (18,333 ft)) and 11 flights by C-141 aircraft (6.7 h and 10,744 m (35,250 ft)). RESULTS: Mean minimum temperatures for the C-130 remained above freezing and averaged 5.1 degrees C for FW and 11.9 degrees C for SW. The higher, longer C-141 flights produced temperatures below freezing with mean minimum temperatures of -18.0 degrees C for FW and -12.4 degrees C for SW. In general, temperatures in wheel-wells remained about 20 degrees C above outside air temperature (OAT) at all altitudes. This increase reflects the fact that wheel-wells are closed spaces within the aircraft body, in addition to which they contain sources of heat such as hydraulic lines and electrical equipment. Cargo compartment minimum temperature was relatively high (mean = 18.6 degrees C for commercial airline). A search of the medical literature and lay press produced information on 46 incidents of people found in wheel-wells after landing where there was no evidence of trauma. The 15 survivors had stowed away on relatively short flights (mean = 4.8 h, maximum = 10 h) compared with fatalities (mean = 7.5 h, range = 3-12 h). CONCLUSIONS: Temperatures in wheel-wells during short flights may sustain life. Long flights add severe hypothermia to acute hypoxia and hypobaria as potentially fatal environmental factors faced by wheel-well stowaways.

Pulmonary vascular response of the coati to chronic hypoxia.

The unusually muscular pulmonary arteries normally present in cattle and swine residing at low altitude are associated with a rapid development of severe pulmonary hypertension when those animals are moved to high altitude. Because these species lack collateral ventilation, they appear to have an increased dependence on hypoxic vasoconstriction to maintain normal ventilation-perfusion balance, which, in turn, maintains thickened arterial walls. The only other species known to lack collateral ventilation is the coati, which, similarly, has thick-walled pulmonary arteries. We tested the hypothesis that coatis will develop severe high-altitude pulmonary hypertension by exposing six of these animals (Nasua narica) to a simulated altitude of 4,900 m for 6 wk. After the exposure, pulmonary arterial pressures were hardly elevated, right ventricular hypertrophy was minimal, there was no muscularization of pulmonary arterioles, and, most surprising of all, there was a decrease in medial thickness of muscular pulmonary arteries. These unexpected results break a consistent cross-species pattern in which animals with thick muscular pulmonary arteries at low altitude develop severe pulmonary hypertension at high altitude.

La hemoglobina, es un marcador genético invariable: hallazgos en la gallina criolla andina / The hemoglobin is a genetic marker invariability: Andean chicken finding

La gallina doméstica (Gallus gallus) fue inducida en Sud-América con la conquista española. Esta (Gal-NM), presenta una baja afinidad de la hemoglobina por el O2 (Hb-O2) e hipereritremia. Sin embargo hemos encontrado en Taraco (Puno, 4,000 m), y reproducido a nivel del mar, un grupo de gallinas con una alta afinidad de la Hb-O2 y ausencia de la hiperetremia (Gal-ALT). La afinidad de la Hb-O2(P50) fue determinada por el método de las mezclas en sangre total y en Hb libre de fosfatos (Hb-Lavada) antes y despúes de la adición de inositol hexafosfato (IHP) . La adición de la IHP se comportó de manera diferente en las dos hemoglobinas lavadas. La diferencia (Hb-lavada-Hb+IHP) fue 42.2 torr para Gal-NM y 26.3 torr para Gal-ALT, lo que es una indicación de que Hb de la Gal-ALT es fosfato-dependiente. Una mutación, Thr-->Ser, encontrada en la posición 69 de la cadena ß podría haber inducido la fosfato-dependencia. Nuestro hallazgo muestra un cambio en la función de la Hb, adquirido en un período evolutivo extremadamente corto de aproximadamente 500 años; muestra también, que individuos de una misma especie, que viven a NM y en la altura, pueden diferenciarse genéticamente mediante un cambio en la función de la Hb como reflejo de un cambio en su estructura.