Mechanisms of human adaptation to hypoxia

The effects of adaptation to cold-and-hypoxic exposure on the cardiovascular system, lipid peroxidation and concentrations of adaptogenesis involved hormones were studied in male students. The two weeks cold- and hypoxic training was shown to be accompanied by a significant increase of apnea duration, reduced velocity of bradycardia development and a more rapid ECG post-cold and- hypoxic exposure normalization, as well as by inhibition of activation of adrenal cortex and thyroid gland after stress of different nature. The changes of the character of influences between the indices under study, were demonstrated. The correlation analysis showed an increase of the human's adaptive potential and a decrease of its dependence on the adrenal cortex hormones.     

Microcirculatory changes during chronic adaptation to hypoxia

Microcirculatory changes in the window chamber preparation in Syrian golden hamsters, secondary to chronic hypoxia adaptation, are presented herein. Adaptation was attained by keeping animals in a 10% oxygen environment for 1 wk and 5% the following week. The following groups were studied: group 1, adapted to chronic hypoxia and kept in a 5% oxygen environment throughout the experiment; group 2, adapted to chronic hypoxia and kept in a 21% oxygen environment 24 h before and during the experiment; and group 3, control. Adaptation caused venule enlargement and hematocrit increase (68.6 +/- 2.44 in group 1, 70 +/- 2.66 in group 2, and 43.27 +/- 2.30 in group 3; P < 0.05). Whereas heart rate decreased in adapted animals, blood pressure remained constant. Group 1 presented alkalosis, hypocapnia, and hypoxemia. The adapted groups had decreased blood flow velocity in arterioles and veins. We found no difference in microvasculature oxygen tension between groups 2 and 3; however, the number of capillaries with flow was markedly reduced in group 1 but significantly increased in group 2. Our findings suggest that, as an adaptation to hypoxia, erythropoiesis may prove beneficial by increasing blood viscosity and shear stress, leading to vasodilatation, in addition to the increase in oxygen-carrying capacity. Calculations show that oxygen extraction in the tissue of the window chamber model was significantly lowered in adapted animals breathing 5% oxygen, but was unchanged from the control when breathing 21% oxygen, even though blood hemoglobin content was increased from 14.5 +/- 0.07 g/dl at control to 21.04 +/- 1.24 g/dl in the adapted animals (P < 0.05).     

NO-dependent effects during adaptation of rats to intermittent hypoxia

In experiments on Wistar rats processes nitric oxide production on concentration of anions (NO2-, NO3-), carbamide and polyamines contents were investigated in processes of rats adaptation to acute hypoxia (7% O2 in N2, 30 min) and intermittent hypoxia training (10% O2 in N2, 15 min, 5 cycles daily) during 14 days. NO production by oxygen-dependent and oxygen-independent metabolites paths has been investigated. It is concluded that the disturbances in nitric oxide system induced by acute hypoxia by L-arginine injections may result in acute hypoxia.     

Effect of intermittent hypoxic hypoxia on energy supply of rat skeletal muscle during adaptation to physical load

The experiment, on Wistar male rats was carried out to investigate influence of endurance training (swimming with load 7.0 +/- 1.3% body weight, 30 min a day, during 4 weeks) and additional intermittent hypoxic training (12% O2 in N2 - 15 min, 21% O2 - 15 min, 5 sessions a day, during the first 2 weeks) on the following parameters: ADF-stimulated mitochondrial respiration, lactate/pyruvate ratio, succinate dehydrogenase activity, and lipid peroxidation in skeletal muscle. The next oxidation substrates were used: 1 mmol/l succinate and 1 mmol/l alpha-ketoglutarate as well as the next inhibitor succinate dehydrogenase 2 mmol/l malonate. It was shown that physical work combined with intermittent hypoxic training led to the increase of mitochondrial respiration effectiveness in muscle energy supply under alpha-ketoglutarate oxidation in comparison with succinate oxidation as well as to the decrease of succinate dehydrogenase activity and lipid peroxidation. The study suggested that these changes may correct mitochondrial dysfunction under intensive muscular work.     

Rates of energy substrates utilization during human cold exposure

Although it is well established in animals that acute cold exposure markedly increases the oxidation of energy substrates, the absolute quality and quantity of substrate oxidation is poorly understood in humans. This study compared the rates of substrate utilization in seven healthy young men exposed to both the warm (control exposure at 29 degrees C; semi-nude, 14 h fasted) and to the cold for 2 h (10 degrees C, 1 m.s-1 wind velocity). Substrate utilization was calculated using indirect calorimetry and the nonprotein respiratory exchange ratio, which was derived from the urinary urea nitrogen output. Cold exposure induced a 3.1 +/- 0.2 degrees C drop in mean body temperature and a body heat debt of 825.9 +/- 63.3 kJ (p less than 0.01). These parameters remained essentially unchanged in the warm. Cold exposure elevated the 2 h energy expenditure 2.46-fold in comparison to the warm (p less than 0.01). This cold-induced thermogenesis was accompanied by increases of 588% in carbohydrate oxidation (p less than 0.01) and 63% in fat oxidation (p less than 0.05), whereas protein oxidation remained unchanged. Although the greatest proportion of the energy expenditure in the warm was derived from lipid (59%), carbohydrate oxidation represented the major fuel for thermogenesis in the cold, since it accounted for 51% of the corresponding total energy expenditure. The results demonstrate that cold exposure causes a much greater increase in the utilization of carbohydrate than lipid. It is suggested that these substrates are directly utilized for thermogenesis in the shivering skeletal muscles.     

Differences in the strategies and potentials of human adaptation to hypoxia

The general patterns and individual specific features of human adaptation to acute hypoxic hypoxia caused by breathing a hypoxic oxygen-nitrogen gas mixture containing 8.0% oxygen have been studied. It was found that, at the initial stage of hypoxia, all examined subjects demonstrated a reduced oxygen consumption as compared to normoxia; then, this parameter increased and, beginning from a certain moment (after 5–15 min of exposure), exceeded the baseline level by 10–40%. Hypotheses explaining the mechanisms of this growth in oxygen consumption during hypoxia are considered. It has been found that the roles of the cardiovascular system and mechanisms of the tissue and cellular utilization of oxygen in the growth of the rate of oxygen consumption caused by hypoxia vary in different subjects. The hypothesis is put forward that the relatively low potential for rearrangement of the biological oxidation system at the cellular level, aimed at increasing the rate of oxygen consumption, predetermines a need to increase the rate of oxygen supply by the blood and, therefore, a greater strain of the cardiovascular system. In many cases, this strain can cause failure of adaptation to hypoxia. Other parameters that can serve as characteristics of a subject’s resistance to hypoxia, such as the intensity of EEG slow waves and the level of blood oxygenation, are also considered.     

Carbohydrate and lipid metabolism in rats during adaptation to cold

Cold adapted rats are shown to have glucose and fatty acids concentration in blood inchanged, lactate concentration increased and triglyceride concentration decreased against the control level. Glucose utilization rate in the tolerance test grows. Glycogen content falls, hexokinase and succinate dehydrogenase activity increases, glucose-6-phosphatase and NAD+-isocytratedehydrogenase activity decreases in the liver of experimental animals. The results indicate that utilization of carbohydrate and lipid substrates for thermogenesis is intensified in cold-adapted rats. The hypothesis is supported by the data of tests dealing with IPNA injection or with bringing the animals back under thermocomfortable conditions.     

Effect of adaptation to hypoxia on the working capacity and energy of skeletal muscles

The authors studied the working capacity and heat formation of the skeletal muscles during contraction in rats--control and those adapted to hypoxia. The force of contraction, the work and fatigueability of the muscles, as well as elevation of the muscle temperature as a result of contraction were determined under conditions of indirect muscle electrostimulation. Hypoxia adaptation failed to influence the force of muscle contraction and the work performed. However, hypoxia led to reduction of the temperature effect of the muscle contraction per unit of the work performed. This pointed to increase of the efficiency of the muscle work in hypoxia adaptation. Fatigueability of the muscles in "hypoxic" rats was elevated. Changes in the energy of the muscle contraction in hypoxia and cold adaptation were different.     

Body temperature regulation during acclimation to cold and hypoxia in rats

Extreme environmental conditions present challenges for thermoregulation in homoeothermic organisms such as mammals. Such challenges are exacerbated when two stressors are experienced simultaneously and each stimulus evokes opposing physiological responses. This is the case of cold, which induces an increase in thermogenesis, and hypoxia, which suppresses metabolism conserving oxygen and preventing hypoxaemia. As an initial approach to understanding the thermoregulatory responses to cold and hypoxia in a small mammal, we explored the effects of acclimation to these two stressors on the body temperature (T_b) and the daily and ultradian T_b variations of Sprague-Dawley rats. As T_b is influenced by sleep-wake cycles, these T_b variations reflect underlying adjustments in set-point and thermosensitivity. The T_b of rats decreased precipitously during initial hypoxic exposure which was more pronounced in cold (T_b=33.4±0.13) than in room temperature (T_b=35.74±0.17) conditions. This decline was followed by an increase in T_b stabilising at a new level ~0.5 °C and ~1.4 °C below normoxic values at room and cold temperatures, respectively. Daily T_b variations were blunted during hypoxia with a greater effect in the cold. Ultradian T_b variations exhibited daily rhythmicity that disappeared under hypoxia, independent of ambient temperature. The adjustments in T_b during hypoxia and/or cold are in agreement with the hypothesis that an initial decrease in the T_b set-point is followed by its partial re-establishment with chronic hypoxia. This rebound of the T_b set-point might reflect cellular adjustments that would allow animals to better deal with low oxygen conditions, diminishing the drive for a lower T_b set-point. Cold and hypoxia are characteristic of high altitude environments. Understanding how mammals cope with changes in oxygen and temperature will shed light into their ability to colonize new environments along altitudinal clines and increase our understanding of how T_b is regulated under stimuli that impose contrasting physiological constraints.     

Growth of cardiac muscle cells during rat adaptation to altitude hypoxia

The weight of the right heart ventricle in 1.5-month-old rats kept after birth in the mountains of 3400 m altitude is higher and its muscle cell cytoplasm mass is much larger compared to those in 1.5-month-old animals raised at 800 m altitude. The hypertrophy of cells is not due to their polyploidization. Only a small increase in the relative number of polyploid cells takes place under high altitude hypoxia. The weight of the right ventricle and myocyte mass in 3-month-old rats kept 1.5-3 months after the birth at 3400 m altitude also increases, although this augmentation is significantly less than in the animals grown in the mountains for 1.5 months immediately after the birth. The myocyte ploidy of adult animals adapted to hypoxia does not essentially differ from that of 1.5- and 3-month-old control rats: about 80 per cent of these cells are polyploid. Thus, the growth of cardiac myocytes under the heart hyperfunction in the case of high altitude hypoxia proceeds mainly on the ground of the stable polyploid genome, as well as normal ontogenetic growth of these cells.