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.

     

Changes in plasma lipids and lipoprotein cholesterol during a high altitude mountaineering expedition (4800 m)

Effects of high altitude exposure on plasma lipids and lipoprotein cholesterol were studied in 8 mountaineers who spent 3 weeks at the Annapurna IV base camp (4800 m) after a 12 day trek. In spite of the moderate physical exertion at the camp, the loss of body weight was more pronounced during the stay at high altitude than during the trekking period. Compared with baseline values observed at sea level, marked reductions in plasma cholesterol (-27%) and phospholipids (-19%) were found 3 days after arrival at the camp and persisted during the next 17 days. A less marked fall in plasma triglycerides occurred, weakly significant at the end of the stay. Because there were no relevant changes in very low density lipoproteins or in high density lipoprotein (HDL)-cholesterol, the low plasma cholesterol levels at the high altitude resulted mainly from the reduction in low density lipoprotein (LDL)-cholesterol: the mean HDL/LDL cholesterol ratio changed from 0.39 at sea level to 0.63 at the end of the stay at 4800 m. Fluctuations in LDL-cholesterol were not concomitant with those in body weight and were independent of the exercise training during the expedition. This study shows moreover that the early drop in LDL-cholesterol was associated with an opposite change in plasma levels of catecholamines and thyroid hormones. Taking into account that such hormonal responses are classically observed at high altitude, the concomitant decrease in LDL-cholesterol might be interpreted as being a relevant adaptative response to hypoxic conditions at high altitude.     

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)     

Responses of calves to a simulated altitude of 5000 m

Six calves were exposed in succession 12 days at 400 m altitude (control), 12 days at a simulated altitude of 5000 m in a low pressure chamber (experimental), and 14 days at 400 m altitude (recovery). Exposure to 5000 m produced the following changes: intake of feed and water decreased by 47 and 35% respectively, and body weight gain ceased. Rectal temperature rose by 0.4°C. Heart rate increased by 65%. Respiratory rate and blood pH increased moderately. There was an S-shaped rise of haematocrit (from 33 to 45%), which was paralleled by blood viscosity. Plasma viscosity showed a sharp, but transient rise. Short term measurements made during ascent to and descent from 5000 m altitude, both lasting for four hours, showed that some of the changes developed rapidly.