Low-altitude Group Research Articles

The Effect of High Altitude on Blood Hormones in Male Westar Rats in South Western Saudi Arabia

Problem statement: Living in high altitude areas results in chronic h ypoxia, which induces complex metabolic and endocrine adaptations. The current study investigated the endocrine responses of male Westar rats chronically exposed to high alt itude-induced hypoxia in Abha City, in Southwestern Saudi Arabia. Approach: The rats were separated in to 2 groups of 10 rats. The first group was kept at an altitude of 600 m above sea le vel in the King Saud University animal house in Riyadh City and designated the low altitude group; the second group of rats was transferred to the King Khalid University animal house in Abha City, which is 2800 m height above sea level and was designated the high altitude group. All rats were h oused under the same laboratory conditions and fed the same diet. Blood samples were collected from bo th groups of animals 45 days after transferring the high altitude group to Abha City. Results: The data revealed that the rats transferred to the high altitude area had significant decreases in serum Th yroid Stimulating Hormone (TSH) and testosterone levels and significant increases in the levels of s erum cortisol, free Triiodothyronine (T3) and free Thyroxin (T4) compared to rats kept at low altitude . Conclusion: The current study demonstrates that rats chronically exposed to high altitude hypoxia e xperienced alternations in various hormones. These findings will contribute to a better understanding of human endocrine and metabolic physiology in hypoxic conditions. Key word: High altitude, hormones, TSH, testosterone, Saudi A rabia

Comparison of the pharmacokinetics of sulfamethoxazole in male chinese volunteers at low altitude and acute exposure to high altitude versus subjects living chronically at high altitude: An open-label, controlled, prospective study

Background: Sulfamethoxazole is an antibacterial sulfonamide used primarily for the treatment of a wide variety of bacterial infections in combination with trimethoprim. Despite being used as prophylactic treatment for respiratory infections associated with high altitude, little information is available on the pharmacokinetic properties of sulfamethoxazole in subjects living at high altitude, especially in a Chinese population. Objective: This study was conducted to investigate the pharmacokinetics of sulfamethoxazole in healthy Chinese subjects after acute and chronic exposure to high altitude. Methods: An open-label, controlled, prospective study was conducted in healthy Chinese male volunteers. Sulfamethoxazole 1200 mg was administered orally to volunteers in 3 groups: those residing at low altitude (~400 m [~1300 ft]); these same volunteers after 16 hours (acute) of exposure to high altitude (~3780 m [~12,400 ft]); and a separate group of volunteers who had been living at high altitude (~3780 m) for ≥1 year (chronic). The phases of the low-altitude and acute-exposure groups were separated by a 1-week washout period. Blood samples were collected from an indwelling venous catheter into heparinized tubes before (baseline) study drug administration and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, and 48 hours after study drug administration. Sulfamethoxazole in whole blood, plasma, and plasma water, and its metabolite, N 4-acetyl-sulfamethoxazole, in plasma were determined by HPLC. Tolerability was determined using blood chemistry testing, continuous 12-lead ECG, and blood pressure monitoring. Results: A total of 23 healthy Chinese male volunteers living at low altitude (race, all Han Chinese; mean [SD] age, 20.4 [1.1] years [range, 19–24 years]; weight, 64.2 [5.9] kg [range, 56.0–75.0 kg]; and height, 172.1 [4.9] cm [range, 163.0–180.0 cm]) and 21 healthy Chinese male volunteers living at high altitude (race, all Han Chinese; mean [SD] age, 21.2 [1.3] years [range, 19–24 years]; weight, 62.4 [8.2] kg [range, 50.0–75.0 kg]; and height, 171.4 [5.8] cm [range, 162.0–182.0 cm]) were enrolled in the study; 20 from each group completed the study. Concentration of sulfamethoxazole in plasma water decreased significantly after exposure to high altitude; therefore, the protein binding was significantly higher in the acute- (80.4%) and chronic-exposure (72.5%) groups compared with the low-altitude group (65.7%; both, P < 0.001). The binding of sulfamethoxazole to red blood cells was 6.0%, 6.9%, and 9.3% in the low-altitude, acute-, and chronic-exposure groups, respectively. The chronic-exposure group was 55% higher than the low-altitude group ( P < 0.001). The following values were recorded in the low-altitude, acute-, and chronic-exposure groups after administration of sulfamethoxazole, respectively: mean (SD) t ½, 9.30 (1.11), 10.37 (0.88), and 11.15 (1.53) hours; mean residence time (MRT 0–48), 12.06 (0.94), 13.15 (0.67), and 13.00 (1.01) hours; elimination rate constant (k e), 0.076 (0.010), 0.067 (0.006), and 0.063 (0.009) hours −1; AUC 0–48, 1202.5 (238.3), 1416.3 (202.6), and 1298.5 (256.0) μ/mL/h; and clearance (CL), 1.01 (0.22), 0.83 (0.13), and 0.92 (0.22) L/kg/h. The t ½ was 11.5% and 19.9% higher in the acute- and chronic-exposure groups, respectively, compared with the low-altitude group, and 7.5% higher in the chronic-exposure group than in the acute-exposure group. MRT was 9.0% and 7.8% higher in the acute- ( P < 0.05) and chronic-exposure ( P < 0.001) groups, respectively, than in the low-altitude group. AUC 0–48 was 17.8% higher and CL was 17.8% lower in the acute-exposure group compared with the low-altitude group (both, P < 0.05). Conclusion: This study found significant changes in the disposition of sulfamethoxazole in these healthy male Chinese subjects after either acute or chronic exposure to an altitude of ~3780 m in comparison to those residing at an altitude of ~400 m.

Age-related changes in the incidence of pineal gland calcification in Turkey: A prospective multicenter CT study

The goal of this cross-sectional observational study was to determine the incidence of pineal gland calcification (PGC), to investigate the interaction of PGC and aging, and to compare the incidence of PGC among the populations living in Turkey. In a prospective study the rate of PGC on CT scans of 1376 individuals in six referral centers from different regions of Turkey was investigated, with emphasis on effects of climatological parameters and aging on PGC. It was found that the incidence of PGC increased rapidly after first decade and the increase remains gradual thereafter, higher in males than in females for all age groups. There was a significant difference for incidence and degree of PGC between different clinics and between both sexes ( p < 0.001). In addition, there was a significant difference for the degree of PGC between the clinics in low altitude group and those in high altitude group ( p < 0.001 for each). Logistic regression analysis revealed that age, sex, altitude and intensity of sunlight exposure significantly affected the risk of PGC (odds ratios (OR) 1.335, 95% confidence intervals (CI) 1.261–1.414, p < 0.001; OR 1.900, 95% CI 1.486–2.428, p < 0.001; OR 0.715, 95% CI 0.517–0.990, p < 0.05; OR 0.997, 95% CI 0.994–0.999, p < 0.01, respectively). Furthermore, by multiple linear regression analysis, high altitude and increased intensity of sunlight exposure were found to affect the degree of PGC ( β = 0.003, p < 0.001). It is concluded that there is a close relationship between PGC and the aforementioned parameters, supporting a link between the development of PGC and these. This study provides some reference data for new clinical studies on the putative role of pineal gland in future.

Improved running economy and increased hemoglobin mass in elite runners after extended moderate altitude exposure

There is conflicting evidence whether hypoxia improves running economy (RE), maximal O(2) uptake (V(O)(2max)), haemoglobin mass (Hb(mass)) and performance, and what total accumulated dose is necessary for effective adaptation. The aim of this study was to determine the effect of an extended hypoxic exposure on these physiological and performance measures. Nine elite middle distance runners were randomly assigned to a live high-train low simulated altitude group (ALT) and spent 46+/-8 nights (mean+/-S.D.) at 2860+/-41m. A matched control group (CON, n=9) lived and trained near sea level ( approximately 600m). ALT decreased submaximal V(O)(2) (Lmin(-1)) (-3.2%, 90% confidence intervals, -1.0% to -5.2%, p=0.02), increased Hb(mass) (4.9%, 2.3-7.6%, p=0.01), decreased submaximal heart rate (-3.1%, -1.8% to -4.4%, p=0.00) and had a trivial increase in V(O)(2max) (1.5%, -1.6 to 4.8; p=0.41) compared with CON. There was a trivial correlation between change in Hb(mass) and change in V(O)(2max) (r=0.04, p=0.93). Hypoxic exposure of approximately 400h was sufficient to improve Hb(mass), a response not observed with shorter exposures. Although total O(2) carrying capacity was improved, the mechanism(s) to explain the lack of proportionate increase in V(O)(2max) were not identified.

Fetal Hypercapnia in High-Altitude Acclimatized Sheep: Cerebral Blood Flow and Cerebral Oxygenation

The authors tested the hypothesis that in the high-altitude acclimatized fetus, hypercapnia has a significantly less effect on cerebral blood flow (CBF) and cerebral oxygenation than that in normoxic sea level controls. In the high-altitude acclimatized fetus (3801 m; maintained from day 30 of gestation to near term; n = 6), by use of a laser Doppler flowmeter with a fluorescent O (2) probe, the authors measured relative CBF (laser Doppler CBF [LD-CBF]), cortical tissue PO(2) (tPO(2)), and sagittal sinus oxyhemoglobin saturation (HbO(2)) in response to 20-minute hypercapnia. They also calculated cerebral O(2)delivery and cerebral fractional O(2) extraction. The authors compared these results to those obtained in near-sea-level control animals (low-altitude group). In response to hypercapnia (arterial PCO(2) = 63+/- 2 torr vs 42+/- 1 torr baseline), high-altitude fetuses showed similar increases in LD-CBF, cortical tPO(2), and sagittal sinus (HbO(2)) as compared with those responses seen in the fetus at low altitude. Nonetheless, these fetuses showed a significantly smaller decrease in cerebral fractional O(2) extraction compared to low-altitude fetuses. In response to hypercapnia in high-altitude, acclimatized, long-term hypoxic fetal sheep, the response of CBF and cerebral oxygenation did not differ significantly from that of low-altitude controls.

Improvement of metabolic syndrome markers through altitude specific hiking vacations

To study the influence of a 3-week hiking vacation at moderate (1700 m) and low altitude (LA) (200 m) on key-markers of the metabolic syndrome, 71 male volunteers (age 36-66 yr old) with the metabolic syndrome [according to the National Cholesterol Education Program's Adult Treatment Panel III (NCEP-ATP III) - or World Health Organization (WHO) - definition] participated in the study and were randomly assigned into a moderate altitude (MA) group (1700 m, no. 36) and a low altitude (LA) group (200 m, no. 35). The 3-week vacation program included 12 moderate- intensity guided hiking tours [4 times/week, 55-65% heart rate maximum (HRmax)] with a total exercise time of 29 h plus moderate recreational activities. Both study groups had a comparable and balanced nutrition with no specific dietary restrictions. Anthropometric, metabolic and cardiovascular parameters were measured 10-14 days before vacation, several times during the 3-week vacation, 7-10 days and 6-8 weeks after return. All participants tolerated the vacation without any adverse effects. Body weight, body fat, waist-circumference, fasting glucose, total cholesterol, LDL-cholesterol (LDL-C), plasma fibrinogen, resting systolic and diastolic blood pressure were significantly decreased over time in both study groups. In the LA group, fasting insulin and homeostasis model assessment (HOMA)-index were significantly decreased one week after return. Relative cycle ergometry performance was significantly increased after return compared to baseline. In both study groups, waist-to-hip ratio (WHR), 2-h oral glucose tolerance test (OGTT), HDL-cholesterol (HDL-C), and triglycerides remained unchanged. The 3-week vacation intervention at moderate and LA had a positive influence on all key-markers of the metabolic syndrome. No clinically relevant differences could be detected between the study groups. A hiking vacation at moderate and LA can be recommended for people with stable, controlled metabolic and cardiovascular risk factors.

Maternal oxygen administration and fetal cerebral oxygenation: Studies on near-term fetal lambs at both low and high altitude

We tested the hypothesis that O2 administration to the mother would increase arterial O2 tension (PaO2) and cortical tissue O2 tension (tPO2) in both the normoxic control fetus and that acclimatized to high altitude, and that this effect might be greater in the high altitude fetus than that at sea level. Pregnant ewes were divided into either low-altitude group or high-altitude group (3820 m; maintained from day 30 of gestation to near-term, term = 145 days; n = 6 each). In near-term fetuses we instrumented the cerebral cortex with tissue PO2-laser Doppler flow probes, and placed arterial catheters. With the ewe breathing either air or 50% O2, we measured fetal arterial and brain tissue PO2 and cerebral blood flow (CBF). In response to maternal O2 administration, in both low- and high-altitude fetuses, PaO2, O2 content, and brain tissue PO2 increased significantly. Nonetheless, the fetuses at high altitude showed significantly greater increase in both PaO2 and cerebral tPO2, than that seen in fetuses at low altitude. In neither group was there a change in CBF or cerebral metabolic rate for O2. Maternal O2 administration significantly increased PaO2 and cerebral tPO2 of the fetus both at low altitude and at high altitude, with this increase being greater in the high altitude animals. We suggest that maternal O2 administration can have an important effect in ameliorating nonreassuring fetal status, and perhaps be of value in instances of mothers who smoke heavily or with cardiopulmonary disease.

EFFECT OF ALTITUDE TRAINING ON RUNNER'S SKELETAL MUSCLE

811 "Altitude training" has been linked to increases in muscle buffering capacity, oxidative enzymes and capillary density, although most studies have used either animal models, very few subjects, or high altitude. However, athletes rarely exceed elevations of 3000m during "altitude training". Therefore, we investigated the effect of 4 weeks training in low (1000-2000m) or moderate (2000-3000m) altitude on histologic and biochemical factors in the m. vastus lateralis of trained runners. Methods: Training was monitored. Base and interval pace running were characterized by velocity and VO2. VO2max, 5,000m time and O2 deficit were recorded. Three muscle biopsies were taken on each runner (12 women, 27 men, age 18-31, VO2 max 64±2 ml·kg−1·min−1, anaerobic capacity 56±4 ml·kg−1): 1) before 4 weeks sea level control training (0-200m, n=39); 2) before; and 3) after 4 weeks training at sea level (0-200m, n=13), low altitude (1250-1600m, n=13), or moderate altitude (2200-3000m, n=13, altitude groups lived at 2500m). Biopsies were analysed for fiber type and area, capillary density, activities of citrate synthase (CS), phosphofrucktokinase (PFK), 3,4 hydroxyacyl-CoA dehydrogenase (HAD), and buffer capacity. Results were analysed by ANOVA (p≤0.10). Results: There were no initial differences between groups. Training volume and relative intensity were not different between periods. Interval VO2 and velocity were lower at moderate altitude. VO2max improved in both altitude groups. 5,000m time improved only in the low altitude group. Although both fiber type areas were less during sea level training, and higher during experimental periods (in all groups), percent fiber type and capillary density did not change. There were no changes in the enzymes studied except for increased PFK activity in the sea level group during the experimental period. Tissue buffer capacity decreased in the group training at moderate altitude. Conclusions: Low altitude training is similar to sea level training. In contrast to previous work, moderate altitude training is associated with reduced tissue buffering capacity, no improvement in enzyme activities or capillary density, and may impair sea level performance.

Heart rate variability in 1-day-old infants born at 4330 m altitude

In fetuses and newborn infants heart rate variability changes in conditions of acute and chronic hypoxia; we therefore asked whether heart rate variability of infants born at high altitude differed from that of low-altitude infants. Short-term recordings (4–5 min) of inter-beat intervals were obtained in 19 infants in Lima (50 m altitude) and in 15 infants in Cerro de Pasco (4330 m, barometric pressure ∼ 450 mmHg, inspired oxygen pressure ∼ 94 mmHg) during quiet rest in warm conditions (ambient temperature, Ta, ∼ 35 °C). In 12 infants from each group recordings were also obtained during cooling (Ta ∼ 26 °C). Heart rate variability was evaluated from 512 consecutive inter-beat intervals, with analysis based on time-domain and frequency-domain methods. At warm Ta, heart rate variability did not differ between the two groups. During cooling, heart rate increased only in the low-altitude group. As in the warm, during cooling most parameters of heart rate variability did not differ between the two groups. The only exception was the inter-beat interval power of the high-frequency range of the spectrum (0.15–0.4 Hz), which, at least in adults, is believed to be a reflection of vagal activity, and was greater in the high-altitude group. It is concluded that gestation at high altitude, despite its blunting effects on fetal growth, does not have a major impact on heart rate variability of the newborn. Nevertheless, the possibility that differences in response to cooling may reflect some limitation in heart rate control needs to be examined further.

Heart rate variability in 1-day-old infants born at 4330 m altitude

In fetuses and newborn infants heart rate variability changes in conditions of acute and chronic hypoxia; we therefore asked whether heart rate variability of infants born at high altitude differed from that of low-altitude infants. Short-term recordings (4-5 min) of inter-beat intervals were obtained in 19 infants in Lima (50 m altitude) and in 15 infants in Cerro de Pasco (4330 m, barometric pressure approximately 450 mmHg, inspired oxygen pressure approximately 94 mmHg) during quiet rest in warm conditions (ambient temperature, Ta, approximately 35 degrees C). In 12 infants from each group recordings were also obtained during cooling (Ta approximately 26 degrees C). Heart rate variability was evaluated from 512 consecutive inter-beat intervals, with analysis based on time-domain and frequency-domain methods. At warm Ta, heart rate variability did not differ between the two groups. During cooling, heart rate increased only in the low-altitude group. As in the warm, during cooling most parameters of heart rate variability did not differ between the two groups. The only exception was the inter-beat interval power of the high-frequency range of the spectrum (0.15-0.4 Hz), which, at least in adults, is believed to be a reflection of vagal activity, and was greater in the high-altitude group. It is concluded that gestation at high altitude, despite its blunting effects on fetal growth, does not have a major impact on heart rate variability of the newborn. Nevertheless, the possibility that differences in response to cooling may reflect some limitation in heart rate control needs to be examined further.

508 Effect of Altitude on the Amniotic Fluid Index

The effect of altitude on amniotic fluid volume has not been studied previously. We sought to determine whether there is such an effect by measuring the amniotic fluid index (AFI) in pregnant women at low and high altitudes. We compared populations of pregnant women at two institutions, one located at low elevation (100 ft) and the other at relatively high altitude (6,000 ft). Uncomplicated singleton pregnancies between 20 and 42 weeks' gestation with adequate dating criteria were studied. Patients were excluded if any condition known to alter amniotic fluid volume was present. Data were stratified by gestational age at two-week intervals for analysis. The pregnant women at high altitude (n = 364) had a significantly increased (P < .001) AFI throughout gestation as compared to the low-altitude group (n = 514). The mean difference in the AFI between the two populations for the two-week intervals was 1.5 cm (95% confidence interval, 1.0-2.0). As compared to the low-altitude group, the high-altitude population had a greater proportion of women with polyhydramnios (5.8% versus 1.0%, P < .001) and fewer patients with oligohydramnios (2.5% versus 5.6%, P < .001) after categorization of AFI values utilizing previously established nomograms. This finding suggests that there is an association between high altitude and an increase in the AFI. The mechanism and clinical significance of this effect are unknown.

Vibration syndrome--with special reference to the effects of temperature on vibration-induced white finger.

AbstractIn order to clarify the effects of temperature on vibration‐induced white finger, two groups of chain saw operators in the forestry industry served as the subjects of this study. One group worked at a cold high altitude; the other group worked at a warm low altitude. Except for the difference in temperature, these two groups had similar work environments. The high altitude group had a high prevalence of white finger (75%), but none of the low altitude group suffered from this circulatory disturbance. After measuring the skin temperature and analyzing the results of the cold provocation test, we demonstrated that low temperature is an important factor in causing vibration‐induced white finger.