Dynamics of the mass of the right ventricle of the heart and concentration of RNA in it during the process of "reverse" development of hypertrophy]

Experiments were conducted on male rats, 250-300 g in weight. Adaptation to high altitude hypoxia was created by placing the animals daily for 5 hours, into an altitude chamber, at an "altitude" of 6000 m. The degree of hypertrophy of the right ventricle and its RNA content was studied after 20 days of adaptation, as well as 2, 10, 20 and 40 days after cessation of hypoxia. Twenty days after the beginning of adaptation the muscle mass of the right ventricle the RNA concentration and amount in it was found to increase considerably. After cessation of hypoxia half of the acquired increase in the ventricle muscle mass was lost in 10 days, and half of the acquired increase in the RNA--as soon as in 2 days. Forty days after cessation of hypoxia the right ventricle mass and its RNA content in the adapted animals did not differ from the same indices in control rats.     

Effects of adaptation to intermittent high altitude hypoxia on ischemic ventricular arrhythmias in rats

We compared the effects of adaptation to intermittent high altitude (IHA) hypoxia of various degree and duration on ischemia-induced ventricular arrhythmias in rats. The animals were exposed to either relatively moderate hypoxia of 5000 m (4 or 8 h/day, 2-3 or 5-6 weeks) or severe hypoxia of 7000 m (8 h/day, 5-6 weeks). Ventricular arrhythmias induced by coronary artery occlusion were assessed in isolated buffer-perfused hearts or open-chest animals. In the isolated hearts, both antiarrhythmic and proarrhythmic effects were demonstrated depending on the degree and duration of hypoxic exposure. Whereas the adaptation to 5000 m for 4 h/day decreased the total number of premature ventricular complexes (PVCs), extending the daily exposure to 8 h and/or increasing the altitude to 7000 m led to opposite effects. On the contrary, the open-chest rats adapted to IHA hypoxia exhibited an increased tolerance to arrhythmias that was even more pronounced at the higher altitude. The distribution of PVCs over the ischemic period was not altered by any protocol of adaptation. It may be concluded that adaptation to IHA hypoxia is associated with enhanced tolerance of the rat heart to ischemic arrhythmias unless its severity exceeds a certain upper limit. The opposite effects of moderate and severe hypoxia on the isolated hearts cannot be explained by differences in the occluded zone size, heart rate or degree of myocardial fibrosis. The proarrhythmic effect of severe hypoxia may be related to a moderate left ventricular hypertrophy (27 %), which was present in rats adapted to 7000 m but not in those adapted to 5000 m. This adverse effect can be overcome by an unknown protective mechanism(s) that is absent in the isolated hearts.     

Sex-related patterns of body tolerance to repeated acute hypobaric hypoxia

The individual differences in the response of male and female rats to repeated exposure to acute hypobaric hypoxia were experimentally studied. The time of attitudinal reflex maintenance and recovery in a rotating decompression chamber as well as the value of hypoxic hypothermia after decompression to a simulated altitude of 11200 m were used to evaluate the tolerance to hypoxia. Males demonstrated a slightly higher reactivity than females. At the same time, a more efficient adaptation to hypoxia conserved the body’s compensatory capacity and rapidly restored the functions affected by repeated exposure to the extreme factor. Such long-term adaptation was observed in initially low-resistant females, which could increase their resistance to repeated exposures to the stress factor.     

Comparison of cardiopulmonary responses of male and female rats to intermittent high altitude hypoxia

Intermittent high altitude hypoxia (8 hours a day, 5 days a week, stepwise up to the altitude of 7000 m, total number of exposures 24) induced in male and female rats, chronic pulmonary hypertension and right ventricular hypertrophy. No significant sex differences were found in both these parameters. A significant sex difference was demonstrated in the resistance of the cardiac muscle to acute anoxia in vitro: the myocardium of control female rats proved to be significantly more resistant to oxygen deficiency. Intermittent altitude hypoxia resulted in significantly enhanced resistance in both sexes, yet the sex difference was maintained. Sex differences were further observed in the growth response of experimental animals to the acclimatization process. Whereas the body weight of male rats exposed to intermittent altitude hypoxia was significantly lower, hypoxic females had body weights comparable to those of control animals.     

藏羚羊和藏系绵羊血液内分泌激素水平的比较研究

为了探讨藏羚羊适应高原环境的内分泌系统的功能特点,我们对藏羚羊(9只)和藏系绵羊(10只)进行了内分泌激素水平的比较。在海拔4300m地区捕获到动物后,随即运至海拔2800m实验基地,次日早晨抽取右侧颈静脉血,采用放射免疫法(radioimmunoassay,RIA)或酶联免疫吸附实验法(enzyme-linked immunosorbent assay,ELISA)测定下丘脑-腺垂体-外周腺轴20项内分泌激素水平,用导管插入术记录动物心率(heart rate,HR)、收缩压(systolic blood pressure,SBP)、舒张压(diastolic bloodpressure,DBP)和平均肺动脉压(mean pulmonary arterial pressure,mPAP)。使用血细胞分析仪测定血红蛋白(hemoglobin,Hb)含量。结果显示,藏羚羊血液中FT3、FT4、AngⅡ水平显著低于藏系绵羊,而藏羚羊血液中TRH、CRH、F、GHRH、E2、Ald、ACTH、CGRP水平则显著高于藏系绵羊。相对于藏系绵羊,藏羚羊HR、mPAP、SBP、DBP和Hb含量明显较低。藏羚羊和藏系绵羊的H...     

急性低氧对高原土生动物藏系绵羊血气的影响

为了探讨急性低氧时藏系绵羊(Ovis aries)的血气特点,揭示其低氧适应机制,将7只雄性藏系绵羊和5只雄性移居绵羊分别置于高低压氧舱内,测定模拟海拔0、2 300和4 500 m时各动物清醒状态下的血气指标。用热稀释法测定心输出量。使用血气分析仪和EG7血样板,测定动脉及混合静脉血的血气指标,按Ficks方法计算氧耗量。结果显示,随着模拟海拔高度的升高,藏羊和移居羊的动静脉血氧饱和度(So2)、氧分压(Po2)、二氧化碳分压(Pco2)都呈明显下降趋势(P<0.05),血红蛋白浓度(Hb)、血液pH、心输出量及氧耗量虽无明显的差异性改变,但它们在4 500 m处的绝对值是增加的。在相同海拔,藏羊的Hb明显低于移居羊(P<0.05),4 500 m时藏羊的动脉血氧饱和度(Sao2)及组织摄氧量显著高于移居羊(P<0.05)。表明藏羊在急性低氧时表现出的高Sao2及高组织摄氧量,低Hb、低pH是它适应高原低氧的生理基础。     

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).     

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.     

Changes in conditioned reflex activity during adaptation of the rat to pressure-chamber and high-altitude hypoxia

A group of rats with a stereotype of conditioned reflexes was preliminarily trained to hypoxia effects during 30 days (at the "altitude" of 6000 m, time of exhibition--from 10 to 60 min, for 18 days--only 60 min). Adaptive changes in the process of training consisted in a weakening of differentiation inhibition, partial amnesia of the conditioned reaction of active avoidance and appearance of phasic states (equalization and paradoxical phases) in the cerebral cortex. The following adaptation of hypoxia "trained" rats to new natural conditions of Alpine altitude (3200 m) proceeded favourably, without disturbance of differentiation inhibition and without phasic states. Rats without preliminary training to altitude chamber hypoxia, in mountains (3200 m) were subjected to moderate tension resulting in protective inhibition, partial amnesia and transient disturbance of differentiation inhibition.     

Intensity of RNA synthesis and the DNA content in the myocardium of newborn rats during adaptation to altitude hypoxia

Newborn rats were exposed to staged adaptation to altitude hypoxia in a pressure chamber at an atmospheric pressure corresponding to an altitude from 2000 to 9000 m. The time course of changes in the synthesis of RNA and DNA by the nuclei of muscle and connective tissue cells of the heart were studied by light autoradiography with the use of 3H-5-uridine and 3H-thymidine. In the course of early postnatal ontogenesis adaptation to altitude hypoxia was demonstrated to be accompanied by the intensified synthesis of nucleic acids by muscle and non-muscle cells of the heart, which is regarded as a compensatory-adaptation reaction of the myocardium to hyperfunction under the test experimental conditions.     

低氧对横断脊髓大鼠脊髓反射兴奋性的影响

本文用低压舱模拟不同海拔高度,测定横断脊髓大鼠脊髓反射兴奋性恢复曲线。断脊髓组和对照组自海拔２０００ｍ以后脊髓反射兴奋性逐渐增高,但两组出现差异有显著性的海拔高度不同,断脊髓组为海拔４０００ｍ,对照组为海拔３０００ｍ。对照组与断脊髓组在同一海拔高度上比较,除海拔３０００ｍ时差别有显著性（Ｐ＜０．０５）外,在其它各海拔高度上两组间差异无显著性（Ｐ＞０．０５）。结果表明,低氧时脊髓以上中枢和脊髓都参与脊髓反射兴奋性升高的调节     

低氧对雄性高原鼠兔性腺的影响

在人工模拟低氧环境下（低压舱模拟５０００ｍ和７０００ｍ海拔高度）,低氧暴露２４ｈ和７ｄ,观察低氧对受试动物性腺的影响。结果表明,急性低氧２４ｈ,高原鼠兔血浆雌二醇（Ｅ２）明显升高;低氧暴露７ｄ,高原鼠兔血浆Ｅ２仍维持一较高水平;５０００ｍ低氧暴露７ｄ,其睾丸指数无明显变化,７０００ｍ时却有所降低。同等条件下,大鼠睾丸指数明显增高;５０００ｍ和７０００ｍ低氧暴露７ｄ对高原鼠兔睾丸组织形态无明显影响,然而,大鼠曲细精管间隙增大,且曲细精管内各级细胞排列紊乱。低氧环境下,高原鼠兔雄体血浆Ｅ２增高,可能是其低氧适应的特征之一     

Certain mechanisms of development of types of body tolerance to acute hypobaric hypoxia

The regulatory mechanisms of individual rat resistance to acute hypobaric hypoxia were studied using the functional indices of the central nervous system (neurochemical and behavioral) and the hematopoietic system. The resistance to hypoxia was evaluated by the time of attitudinal reflex maintenance and recovery after decompression to a simulated altitude of 11 200 m. Animals with different types of tolerance to hypoxia demonstrated different metabolic backgrounds of neurochemical processes (which were most balanced in moderately resistant rats). This agrees with the differences in active behavior and adaptive efficiency of these animals exposed to mild open-field stress. High functional activity of erythropoiesis and early leukocytic response were observed in hypoxia-tolerant rats.     

Study of the respiratory sensation on high-altitude andeans

The respiratory sensation and some routine cardiorespiratory parameters were studied on native Highlanders from the Argentine Andes and on Lowlanders from Europe, already tested during previous high altitude expeditions. The tests were performed at various altitude levels from 2688m e.i., the village altitude for Highlanders, to 5600m during an expedition to Mt. Aconcagua (6990m). At rest, the perception of 4 external inspiratory resistive loads (ranged between 2.5 and 13 cm.H2O.L-1.s) can allow us to fix by discrimination the sensitivity index P(A) independently of response bias (B) according to Sensory Decision Theory (SDT). The Andean highlanders did not experience the respiratory sensation at the same limits as the European lowlanders well adaptated to high altitude. At higher altitudes than their village altitude, their respiratory sensation presented a lower threshold of perception and a weaker discrimination which might be partly explained by the evolution of some parameters of their cardio-respiratory function when altitude increased. Indeed, in response to high altitude hypoxia (5600m), they increased their respiratory frequency and not their minuteventilation or mouth pressure. This chosen ventilatory pattern was opposite to the one chosen by the Lowlanders and did not allow for sufficient adaptation to a more important altitude hypoxia than that of their village altitude. In conclusion, the Andean highlanders wellbeing adapted to their village altitude, exhibited a difficult acclimatization to higher altitudes which might be due to the characteristics of their respiratory sensation. These results might explain their weak physical performances during ascent to the Mt. Aconcagua summit in spite of special training.     

Effect of adaptation to hypoxia on the antioxidant enzyme activity in the liver in animals that have undergone stress

It was shown in experiments on rats that emotional-painful stress resulted in a rapid increase in malonic dialdehyde (MDA) and in a decrease in the activity of superoxide dismutase (SOD) in liver. Adaptation to moderate intermittent hypoxia in altitude chamber did not affect MDA and increased hepatic SOD by 65%. Stress exposure caused no change in SOD and MDA, but abruptly reduced the fall of SOD in adapted animals. These data are in accordance with the well-known idea that adaptation to hypoxia prevents the activation of lipid peroxidation and the hepatic damage in stress.     

Structural changes in the rat myocardium in the process of adaptation to high-altitude hypoxia]

Changes in the weight of diverse parts of the heart, in cross-sectional area of myocytes and vascularization of the myocardium were studied in rat experiments under altitude hypoxia (3200 m above the sea level) during adaptation of the animals to hypoxia. Morphologically, the compensatory and adaptive reactions of the rat to hypoxia were shown by its increases weight at the expense of hypertrophy of the right ventricular myocardium. Vascularization of the myocardium augmented synchronously to its growing hypertrophy.     

Spleen and thymus lymphoid tissue in hypoxia (a biometric study)

The spleen and thymus have been studied macro- and microscopically in rats (180-200 g body mass) on the 1st, 3d, 5th, 7th, 14th and 28th days of adaptation to a decreased atmospheric pressure in the altitude chamber corresponding to lifting to 5,000 and 7,500 m (after a preliminary gradual acclimatization) and on the 14th, 28th, 42d, 56th days of readaptation. A relative mass of the organs, the white pulp section area--the transversal section area of the spleen ratio, the summation section area of its lymph nodules have been estimated. In the thymus the cortico-medullary index (CMI) has been defined. A relative mass of the spleen increases during the first week of hypoxia, and during adaptation period it somewhat decreases and stabilizes, remaining higher than in the control. At the altitude of 5,000 m the cross section area of the lymph nodules decreases by 17% on the 28th adaptation day and at the altitude of 7,500 m--by 27% beginning from the 14th up to the 28th adaptation days. In the thymus the CMI, after some decrease during the first days of hypoxia at the altitude of 5,000 m, increases and normalizes on the 28th adaptation day, and at the altitude of 7,500 m stabilizes on the 14th - 28th days of hypoxia. When the rats are at the altitudes of 5,000 and 7,500 m the thymus lymphoid tissue reacts more quickly to the hypoxia effect and much sooner normalizes during the readaptation period than does the white pulp of the spleen. The main changes in the lymphoid tissue of the spleen and thymus take place on the 7th - 28th days of hypoxia.     

Course of experimental cardiac insufficiency under conditions of high altitude depending on the periods of adaptation

The data characterizing the compensatory hyperfunction of the circulation and respiration with dosaged insufficiency of the mitral valve in animals, depending on the periods of adaptation to high-altitude are presented. Unadapted animals with insufficiency of the mitral valve had more serious disorders of hemodynamic and gaseous exchange accompanied by stasis in the lesser and greater circulation. 52.9% of the animals died during the first days after the formation of the mitral defect. In animals adapted to the high altitude hypoxia the process coursed with less pronounced disturbances of circulation and respiration; 28.6% of the animals died.     

Correction of NO-dependent cardiovascular disorders by adaptation to hypoxia

Spontaneously hypertensive rats (SHR-SP) were adapted to intermittent hypobaric hypoxia in an altitude chamber for 40 days. The adaptation to hypoxia prevented an excessive endothelium-dependent relaxation and hypotension characteristic of myocardial infarction. The adaptation also attenuated the increase in blood pressure and prevented impairment of the endothelium-dependent relaxation in SHR-SP. The universal nature of the adaptation allows to use it for correcting many cardiovascular disorders related to diverse alterations of NO metabolism.     

Significance of ATP-sensitive K(+)-channel in the mechanism of antiarrhythmic and cardioprotective effect of adaptation to intermittent hypobaric hypoxia

Adult male Wistar rats were exposed to intermittent hypobaric hypoxia (5000 m, 6 h/day, 6 weeks). It has been found that such mode of adaptation increased cardiac tolerance to arrhythmogenic action of a 45-min coronary artery occlusion but did not change an infarct size/area at risk (IS/AAR) ratio. In a separate series, rats were exposed to stronger intermittent hypobaric hypoxia (7000 m, 8 h/day, 6 weeks) and subjected to 20-min coronary artery occlusion and 3-h reperfusion on the day after the last hypoxic exposure. It has been established that in this case adaptation decreased the IS/AAR ratio, increased cardiac tolerance to arrhythmogenic action of reperfusion but had no effect on the incidence of ventricular arrhythmias occurred during ischemic period. We found that cardioprotective and antiarrhythmic effect of adaptation to the "altitudes" of 7000 m and antiarrhythmic effect of adaptation to the "altitude" of 5000 m is mediated via K(ATP)-channel activation.