Response of the rat cardiovascular system to a moderate altitude in connection with endurance training

The authors investigated whether an altitude of 1,350 m would affect the rat cardiovascular system in the same way as genuine altitude hypoxia and the way it would take effect when combined with endurance training in the form of swimming It was found that 8 weeks spent at this altitude led to an increase in absolute and relative heart weight, to right ventricular hypertrophy, and to increased resistance of the myocardium to acute anoxia. Physical training at a moderate altitude resulted in an increase in the relative weight of the musculature of both the right and the left ventricle and of the septum. Unlike low altitude training, however, growth of the two compartments of the heart was proportional. The resistance of the myocardium of trained animals against anoxia was the same, irrespective of whether they trained at a low or a high altitude. The results show that even a moderate altitude is not a matter of indifference for the rat organism, but that it leads to characteristic manifestations of altitude hypoxia in the cardiovascular system.     

Effects of simulated high altitude (3800 m) on reproductive function in the pregnant rat.

Ovarian appearance, uterine contents (including numbers of fetuses, size and weight), and levels of gonadotropic hormones were studied in pregnant rats exposed to simulated altitude (3800 m). Comparisons were made at 11, 20 and 21 days of gestation between sea level controls rats bred at sea level and placed at reduced barometric pressure on confirmation of pregnancy (SHA). Although fewer fetuses were present in SHA rats on day 11 of gestation, litter size at days 20 and 21 was similar to controls. Body weight and length of SHA fetuses were significantly reduced by day 21 of gestation while placental weights remained similar to controls. The follicle-stimulating hormone (FSH) content in the pituitaries of SHA rats was significantly reduced at days 11 and 21 of pregnancy as compared with controls; luteinizing hormone (LH) content was lower at day 20 than at day 11 among SHA rats. Plasma gonadotropin levels were similar between SHA and control rats all all three stages of gestation. It is suggested that, despite lack of placental adaptation and altered endocrine functions, exposure of rats to hypoxic conditions only during gestation permits better maintenance of pregnancy than reported in rats with longer exposure to high altitude.     

Fluid distribution and tissue thickness changes in 29 men during 1 week at moderate altitude (2,315 m)

To quantify fluid distribution at a moderate altitude (2,315 m) 29 male subjects were studied with respect to tissue thickness changes [front (forehead), sternum, tibia], changes of total body water, changes of plasma volume, total protein concentrations (TPC), colloid osmotic pressure (COP), and electrolytes. Tissue thickness at the forehead showed a significant increase from 4.14 mm to 4.41 mm 48 h after ascent to the Rudolfshuette (2,315 m) (P < 0.05). At 96 h after ascent the tissue thickness at the tibia was decreased to 1.33 mm compared to the control value of 1.59 mm (P < 0.01). Body mass increased from 75.5 kg (control) to 76.2 kg on the last day (P < 0.05) and body water from 44.21 to 45.01 during the week (P < 0.01). The accumulation fluid in the upper part of the body was paralleled by a decrease in TPC and COP. At 48 h after the ascent COP dropped from 29.5 mmHg to 27.5 mmHg (P < 0.01). After 96 h at moderate altitude COP was still significantly decreased compared to the control level. At 1.5 h after the return from the Rudolfshuette in Saalfelden (744m) COP was back to the control values. The TPC also showed an initial drop from 7.75 g · dl^–1 to 7.48 g · dl^–1 after 48 h at altitude and remained below the control value during the whole week (P < 0.01). It seems from our study that even with exposure to moderate altitude measurable fluid shifts to the upper part of the body occurred which were detected by our ultrasound method.     

Influence of altitude (3,515 m) birth on the reproductive organs of male rats

Adult male rats were exposed to a simulated altitude of 3,515 m continuously for a period of 7, 14 and 21 days. There were atrophic changes in testis, epididymis and vas deferens, fall in levels of GPC and sialic acid and increase in alkaline and acid phosphatase activity of these organs. Sperm quality deteriorated. The adverse effects of hypoxia were more pronounced if the exposure was extended to 14 days, but on further increasing the duration of exposure to 21 days, there was a tendency to recover. Male rats born at high altitude (3,515 m), i.e. F₂, F₃ and F₄ generations were used and compared with rats born at sea level. The animals born at HA showed a deterioration of seminal quality, the tests showed lesions, epididymal and vasal physiology were affected. The adverse effects of high altitude were more prominent in F₂ generations, while F₃ and F₄ generations showed adaptation to high altitude.     

Physiological responses of mules on prolonged exposure to high altitude (3 650 m)

Eight healthy male animals were inducted and kept for 2 1/2 years at 3 650 m altitude and subjected to normal work schedules. Physiological measurements viz. heart rate, blood pressure, minute ventilation, oxygen consumption, respiration rate, hemoglobin, packed cell haematocrit volume and eosinophil count were made on these animals at periodic intervals. On acute induction to an altitude of 3 650 m these animals demonstrated a sudden increase in tidal volume, a decrease in Rf and no change in V_E, suggesting a decreased dead space/tidal volume ratio at altitude.However, all these changes stabilised within 3 weeks but on prolongation of stay, the physical state of these animals was adversely affected. The respiratory adjustments occurring on return to sea level appear to be a response to thermal stress. The initial increase in heart rate and blood pressure stabilised by the 2nd week.     

Alterations in the serum electrolyte levels of women during high altitude (4,300 m) acclimatization

Eight, University of Missouri (230 m) college women were exposed for a period of 65 days to an elevation of 4,300 m on Pikes Peak. During the first week of altitude exposure marked increases in the serum levels of chloride, phosphate, proteinate and calcium and marked decreases in the serum levels of sodium, potassium, magnesium and estimated bicarbonate were observed. During the remainder of the altitude sojourn chloride, phosphate, potassium and magnesium reverted toward the initial low altitude value. Serum calcium levels, however, remained elevated during this latter period while sodium levels continued to decrease and proteinate levels continued to increase. There was little or no recovery of the estimated bicarbonate decrement as the period of exposure was prolonged. Two weeks after the subjects returned to Missouri some but not all of the electrolytes returned to their initial levels. Those not recovering completely included calcium, chloride, proteinate and estimated bicarbonate.

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Zusammenfassung Bei acht Studentinnen der Universität von Missouri (230 m) wurden 65 Tage in der Station Pikes Peak (4.300 m) die Elektrolyte im Serum untersucht. Während der 1. Höhenwoche wurde ein deutlicher Anstieg des Chlorids, Phosphats, Proteinats und Calciums und ein deutlicher Abfall des Natriums, Kaliums, Magnesiums und berechneten Bikarbonats im Serum gefunden. In den folgenden Wochen kehrten die Werte des Chlorids, Phosphats, Kalium und Magnesium zu den Werten vor dem Übergang in die Höhe zurück. Der Calciumspiegel blieb dauernd erhöht, der Natriumspiegel fiel weiter ab, und der Proteinatspiegel stieg weiter an. Eine Verbesserung des Bikarbonatspiegels fand nicht statt. Zwei Wochen nach Rückkehr von der Höhe waren fast alle Elektrolytwerte wieder normal ausser Calcium Chlorid, Proteinat und Bikarbonat im Serum.

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Resume Huit étudiantes de l'université du Missouri (230 m d'altitude) ont séjourné durant 65 jours à Pikes Peak (4.300 m d'altitude). Durant ce laps de temps, on a analysé régulièrement les électrolytes du sérum sanguin. Durant la première semaine de leur séjour en altitude, on a constaté une nette augmentation des chlorires, des phosphates, des protéinates et du calcium ainsi qu'une diminution marquée du sodium, de la potasse, du magnésium et de la valeur calculée du bicarbonate. Au cours des semaines suivantes, la valeur des chlorures, des phosphates, de la potasse et du magnésium s'est rétablie au niveau précédant la montée en altitude. Le taux de calcium est resté élevé alors que celui du sodium a continué de baisser et celui des protéinates à s'élever. On n'a pas constaté d'amélioration du taux de bicarbonate. Deux semaines après le retour en plaine, presque toutes les valeurs des électrolytes étaient redevenues normales dans le sérum, à l'exception de celles du chlorure de calcium, des proteinates et du bicarbonate.

     

The influence of altitude and topography on genetic structure in the long-toed salamander (Ambystoma macrodactulym)

A primary goal of molecular ecology is to understand the influence of abiotic factors on the spatial distribution of genetic variation. Features including altitudinal clines, topography and landscape characteristics affect the proportion of suitable habitat, influence dispersal patterns, and ultimately structure genetic differentiation among populations. We studied the effects of altitude and topography on genetic variation of long-toed salamanders (Ambystoma macrodactylum), a geographically widespread amphibian species throughout northwestern North America. We focused on 10 low altitude sites (< 1200 m) and 11 high-altitude sites in northwestern Montana and determined multilocus genotypes for 549 individuals using seven microsatellite loci. We tested four hypotheses: (1) gene flow is limited between high- and low-altitude sites; and, (2) gene flow is limited among high-altitude sites due to harsh habitat and extreme topographical relief between sites; (3) low-altitude sites exhibit higher among-site gene flow due to frequent flooding events and low altitudinal relief; and (4) there is a negative correlation between altitude and genetic variation. Overall F(ST) values were moderate (0.08611; P < 0.001). Pairwise F(ST) estimates between high and low populations and a population graphing method supported the hypothesis that low-altitude and high-altitude sites, taken together, are genetically differentiated from each other. Also as predicted, gene flow is more prominent among low-altitude sites than high-altitude sites; low-altitude sites had a significantly lower F(ST) (0.03995; P < 0.001) than high altitude sites (F(ST) = 0.10271; P < 0.001). Use of Bayesian analysis of population structure (BAPS) resulted in delineation of 10 genetic groups, two among low-altitude populations and eight among high-altitude populations. In addition, within high altitude populations, basin-level genetic structuring was apparent. A nonequilibrium algorithm for detecting current migration rates supported these population distinctions. Finally, we also found a significant negative correlation between genetic diversity and altitude. These results are consistent with the hypothesis that topography and altitudinal gradients shape the spatial distribution of genetic variation in a species with a broad geographical range and diverse life history. Our study sheds light on which key factors limit dispersal and ultimately species' distributions.     

Age-dependent changes of the circadian system

This review summarizes the current knowledge on changes of the circadian system in advanced age, mainly for rodents. The first part is dedicated to changes of the overt rhythms. Possible causes are discussed, as are methods to treat the disturbances. In aging animals and humans, all rhythm characters change. The most prominent changes are the decrease of the amplitude and the diminished ability to synchronize with a periodic environment. The susceptibility to photic and nonphotic cues is decreased. As a consequence, both internal and external temporal order are disturbed under steady-state conditions and, even more, following changes in the periodic environment. Due to the high complexity of the circadian system, which includes oscillator(s), mechanisms of external synchronization and of internal coupling, the changes may arise for several reasons. Many of the changes seem to occur within the SCN itself. The number of functioning neurons decreases with advancing age and, probably, so does the coupling between them. As a result, the SCN is unable, or at least less able, to produce stable rhythms and to transmit timing information to target sites. Initially, only the ability to synchronize with the periodic environment is diminished, whereas the rhythms themselves continue to be well pronounced. Therefore, the possibility exists to treat age-dependent disturbances. This can be done pharmacologically or by increasing the zeitgeber strength. So, some of the rhythm disturbances can be reversed, increasing the magnitude of the light-dark (LD) zeitgeber. Another possibility is to strengthen feedback effects, for example, by increasing the daily amount of activity. By this means, the stability and synchronization of the circadian activity rhythm of old mice and men were improved. (Chronobiology International,17(3), 261-283, 2000)     

Cardiovascular changes during sudden ascent in a cable cabin to the moderate altitude

Our aim was to test the hypothesis that the occurrence of extrasystoles in higher decennia is proportional to the altitude. The occurrence of supraventricular (SVPB) and ventricular (VEB) extrasystoles, values of systolic and diastolic blood pressure and the heart rate were studied in 20 healthy elderly men (50-64 years) during cable cabin transportation to a moderate altitude. These values were measured in stations located at 898 m, 1764 m, and 2632 m above sea level during the transportation in both directions. Our records show that the values of blood pressure and heart rate were within normal limits during the whole period of transportation. Both SVPB and VEB were increasing during the ascent and decreasing to the initial values during the descent compared to the values at altitude of 898 m. The highest values (6 to 7-times exceeding the initial ones) were measured at the summit. The results have demonstrated that the occurrence of SVPB and VEB is proportional to the altitude. The increased incidence in the number of extrasystoles is suggested to be mediated by beta-adrenoceptors.     

Comparison of the reproductive performance of rats at high altitude (3,800m) and at sea level

Estrous cycles and reproductive performance were compared among rats born at high altitude, rats of Berkeley stock transported to 3,800 m, and sea level controls. Disturbances of reproductive function observed in experimental groups were not due to reduced food intake. Estrous cycles of Berkeley stock at 3,800 m were normal, whereas cycles of high altitude native rats were irregular and fertility was impaired. Litter size was reduced in both groups at high altitude with fewer implantation sites than numbers of corpora lutea observed in the Berkeley stock rats at 3,800 m. In the high altitude native animals, numbers of corpora lutea correlated with implantation sites. Placentas from Berkeley stock rats (3,800 m) were heavier than those from the other groups, and fetal hematocrits from these animals were reduced.     

Age-dependent influence of strain rate on the tensile failure of rat-tail tendon

Sensitivity of tensile strength, failure strain, and failure energy density to strain rate was studied for rat-tail tendon (RTT), a collagen-rich connective tissue. Tendons from animals aged 1-27 months were stretched at a high (720 percent/s) and low (3.6 percent/s) strain rate. Each failure parameter increased with strain rate. However, the sensitivity of tendon failure to rate of strain decreased rapidly during growth and sexual maturation of the animal. The study provides basic data on the rate-sensitive strength of collagen fibers using RTT.     

Effects of exposure to a simulated altitude of 3,500 m on calves and oxen

Nine calves and nine oxen were divided into 6 groups and exposed in a climatised low pressure chamber to the following conditions: 2 weeks at 400 m and 4 weeks at 3,500 m. High altitude produced the following changes: increases in heart rate and pulmonary artery pressure, both these changes being larger in the calves than in the oxen. During 4 weeks continuous exposure to 3,500 m, heart rate declined, whereas pulmonary arterial pressure rose. There were increments in respiratory rate, blood-pH, leucocyte number, rectal temperature, blood lactate and blood pyruvate, but no changes in the lactate/pyruvate ratio. Increases in erythrocyte number, haemoglobin, haematocrit, blood specific gravity and blood viscosity were more pronounced in the oxen than in the calves. Feed intake in all animals tended to be depressed in the first half of the high altitude periode. Water intake showed a fall during the first day at 3,500 m, but recovered thereafter. It is concluded that in response to high altitude the calves activated preferentially the circulatory, the oxen the erythropoetic system.     

Growth of lowland native children of European Ancestry during sojourn at high altitude (3,200 m)

The moderate growth retardation frequently observed among children living at high altitude is usually assumed to result from hypoxic stress. However, such children are frequently from the poorer socioeconomic strata of their societies and may suffer malnutrition, poor hygiene, inadequate medical care, and overcrowding—factors also associated with growth retardation. The objective of this study was to determine if there is a statistically observable alteration in the growth of middle-class children of European ancestry during sojourn at high altitude. Semilongitudinal height/weight measurements were gathered retrospectively from medical records of 18 boys and 17 girls who were born at low altitude, were well-nourished and clinically normal, and who had lived at Achoma, Peru (altitude 3,200 m), continuously for 9–36 months. Measurements were divided, by sex, into four cohorts: I (3–6 months at Achoma), II (6–12 months), III (12–18 months), and IV (18–24 months); initial, presojourn, height and weight were also obtained. All heights and weights were normalized with age-specific reference values. Changes in Z scores (ΔZ) during sojourn were calculated for each subject by subtracting the score of the presojourn value from those of cohorts I–IV. Paired t-tests revealed, among the boys, a significant decline in Z score for weight during sojourn in all four cohorts. Weight scores for the girls also declined in all four cohorts, although only the change in cohort III was significant. Height scores showed a decline with time at sojourn in the boys, but in girls there is an initial drop followed by a steady increase to presojourn levels. These results are consistent with the view that moderate hypoxia exerts a primary growth-limiting effect even on healthy, well-nourished children.