Individual resistance of the organism and nerve cell to hypoxia

The correlation between the pattern of a neuron's reaction to acute hypoxia and individual resistance to oxygen deficit is studied on ratsin vivo as well as on surviving slices of their cerebellumin vitro. According to the survival time in a pressure chamber simulating an altitude of 11 km all the rats were divided into groups of high resistance, medium resistance, and low resistance to hypoxia. Survival time was 4.2 times longer in the high resistance group than in the low resistance group. In the cerebellar slices of high resistance animals 61.5% high-resistance neurons and 38.5% low-resistance neurons were recorded. On the other hand, in the high resistance animals the percentage of high-resistance neurons and low-resistance neurons was 31.2 and 68.8, respectively. The period of hypoxia development was 4.32 times longer in the high-resistance neurons as compared to low-resistance neurons. It is speculated that individual differences in the resistance to O₂ deficit are of a hereditary nature and manifest themselves not only on the level of the whole organism, but also in the individual nerve cell. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 11, pp. 454–457, November, 1994     

Comparison of lipid peroxidation parameters in the heart,liver, and brain of rats with different degrees of resistance to hypoxia

The relationship between the intensity of lipid peroxidation and the activity of the antioxidant system in the heart, liver, and brain is studied in male Wistar rats with low and high resistance to hypoxia tested by being “raised” to an altitude of 11.5 km and in intact outbred rats. It is found that in all groups of rats the content of lipid peroxidation products is highest in the liver, lower in the heart, and lowest in the brain. In all groups, the rate of the ascorbate-induced lipid peroxidation is highest in the brain, lower in the liver, and lowest in the heart. The activity of the antioxidant system is highest in the brain, lower in the liver, and lowest in the heart of low-resistance and outbred rats, while in high-resistance rats it is the same in all the organs. Thus, the difference in the parameters of lipid peroxidation and, particularly, of the antioxidant system in the studied organs is most pronounced in rats with a low resistance to hypoxia. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, N ^o 2, pp. 138–143, February, 1996 Presented by A. I. Archakov, Member of the Russian Academy of Medical Sciences     

Effect of various oxygen concentrations on the ATP content in isolated hepatocytes of rats adapted and nonadapted to hypoxia

It is shown that isolated hepatocytes are capable of perceiving slight changes in the envioronmental oxygen concentration. A complicated phase dependence exists between adenosine triphosphate and partial oxygen pressure, which differs in cells from animals with high and low resistance to hypoxia, the former showing a more stable and resistant energy-synthesizing function than the latter. After long-term adaptation to periodic hypoxia, the resistance of the energy-synthesizing function rises in hepatocytes from high-resistant animals, and falls in low-resistant animals suggesting a fundamentally different organization of the emergency compensatory mechanisms of the energy-synthesizing function in hepatocytes of animals of these two types. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 12, pp. 576–581, December, 1994     

Lipid peroxidation parameters in the internal organs of rats with different degrees of resistance to hypoxia

Lipid peroxidation and the antioxidant system of the heart, liver, and brain are studied in adult male Wistar rats with high and low resistance to hypoxia tested by “raising” to an altitude of 11.5 km and in intact outbred rats. These parameters are found to be the same in the brain of low- and high-resistance rats, while the brain content of lipid peroxidation products is higher in both groups of Wistar rats compared with outbred rats. The heart and liver parameters are coupled to the resistance to hypoxia. Antioxidant activity prevails over lipid peroxidation in the hearts and livers of high-resistance rats, confirming that oxidation plays a major role in the damaging and lethal effects of acute hypoxia. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, N ^o 1, pp 26–29, January, 1996 Presented by A. I. Archakov, Member of the Russian Academy of Medical Sciences     

Effect of prenatal hypoxia on DNA synthesis in the tracheal epithelium and LPO-AOD system in the lungs of newborn rats

Newborn rats euthanized 24 h after birth were examined. The rats were born to females exposed to chronic hypobaric hypoxia on days 14–19 of gestation. The index of nuclei labeled with³H-thymidine in the tracheal epithelium of newborn rats exposed to prenatal hypoxia was 3 times lower than in the control. The LPO level was higher in posthypoxic animals than in intact rats. Prenatal hypoxia led to the suppression of antioxidant defense in the lungs of newborn rats. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 117, N ^o 5, pp. 531–533, May, 1994     

Effects of adaptation to periodic hypoxia on kinetic parameters of respiratory chain enzymes in rat brain

A study of kinetic parameters of brain respiratory enzymes revealed that the maximal velocity and the Michaelis apparent constant for NADH-cytochrome C-reductase are significantly lower in low-resistant rats than in rats with a high resistance to hypoxia. Adaptation to periodic hypoxia increases total resistance only in low-resistant rats. It is accompanied by an increase in the values of kinetics parameters for NADH-cytochrome C-reductase and cytochrome oxidase. Kinetic parameters for these enzymes in the brain of high-resistant rats are either unaltered or even decreased. It is suggested that the first enzymatic complex of the respiratory chain is one of the limiting or regulating links in energy metabolism determining the brain's resistance to hypoxia. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, N ^o 3, pp. 252–255, March, 1996.     

Antihypoxic effects of derivative on the EEG power spectra in rats with different susceptibility to oxygen deficiency

The succinate-containing hydroxypyridine derivative yancarb increases both the altitude tolerated by rats and their survival time at a high altitude, particularly in rats with low resistance to hypobaric hypoxia; it also prevents both phasic changes in the EEG characteristic of hypobaric hypoxia and hemispheric asymmetry and paroxysmal activity in the brain of highly resistant rats in the 5000–10,000 m range and in rats with low resistance in the 5000–11,000 m range. Antihypoxic effects of this substance are more pronounced in low-resistance rats and in the left hemisphere of both high- and low-resistant animals; in altitude range of 10,000–13,000 m these effects are weaker or absent. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 7, pp. 57–62, July, 1997     

Effects of adaptation to intermittent hypoxia on oxidative phosphorylation in brain mitochondria of rats with different sensitivities toward oxygen deficiency

After long-term adaptation to intermittent hypoxia, rats with an initially low resistance to acute oxygen deficiency were 2 to 4 times more resistant to it, while highly resistant rats did not show a significant change in resistance. The adaptation was accompanied by weakening of the electron-transporting function of the respiratory chain and increasing efficiency of oxidative phosphorylation in the brain mitochondria oxidizing NAD-dependent substrates, indicating that energy was produced in a more economical way. The succinate oxidase pathway of oxidation was found to be utilized to only a limited extent as a compensatory mechanism in animals exposed to intermittent hypoxia over a prolonged period. The effects of adaptation were more marked in the brain mitochondria of rats initially highly sensitive to oxygen deficiency. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 12, pp. 572–575, December, 1995     

Effect of the season on lipid peroxidation in the myocardium of rats with different resistance to hypoxia

Lipid peroxidation and the antioxidant system of the myocardium of adult male Wistar rats with low and high resistance to acute hypoxia tested by “raising” to an altitude of 11.5 km are studied in winter and in summer. It is found that the winter season is a mild stressor inducing changes in the myocardial antioxidant system and lipid peroxidation which are similar to those observed at the early stages of catecholamine stress in the summer season. In both cases alterations are more pronounced in low-resistance than in high-resistance rats. In winter, in low-resistance rats the intensity of lipid peroxidation and the activity of the antioxidant system are lower, while the ratio of their parameters (chemiluminescence data) is higher. At the same time, the levels of thiobarbituric acid-reactive substances are higher in winter in both groups. The relationship between the studied parameters and the resistance of rats to hypoxia is more obvious in winter than in summer, i.e., it is season-dependent and is also more pronounced in catecholamine stress. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N^olo 7, pp. 87–90, July, 1995 Presented by N. A. Agadzhanyan, Member of the Russian Academy of Medical Sciences     

Effects of adaptation to hypoxia on cytochrome levels in the brain and liver of rats

After a prolonged (for 30 days) adaptation of rats to intermittent hypoxia, their brains contained lowered levels of mitochondrial cytochromes, despite an increase in the number of mitochondria in the brain tissue mass, along with similar levels of high-energy compounds and more protein as compaired to the brains of unadapted controls. A mitochondrial population with novel properties presumably emerged in the brain. These effects were all more strongly marked in rats with an initially low resistance to hypoxia. In the liver of hypoxiaadapted animals, unlike in their brain, cytochrome levels in the mitochondrial and microsomal redox chains were lowered and the biogenesis of mitochondria was much less intensive. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 12, pp. 576–579, December, 1995     

Biotransformation of hepatic xenobiotics in rats with various resistance to hypoxia exposure to after cold

Hepatic monooxygenase activity was studied in rats with various resistance to hypoxia during adaptation to cold. Cold-induced change in the concentrations of cytochromes P-450 and b₅ and the activity of microsomals metabolism of amidopyrine and aniline were shown to be associated with individual resistance to hypoxia. The content of microsomal cytochromes in highly resistant rats did not change on the fifth day of cold exposure. However, the intensity of metabolic reactions decreased. In low-resistance rats, a cold-induced decrease in the concentration of the cytochromes was not accompanied by significant changes in metabolic rates of amidopyrine and aniline. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 12, pp. 631–633, December, 1998     

Criteria of individual and population-wide resistance to acute hypoxia

It is shown that the geometric mean of survival time and the deviation of σ from τ are measures of a population's resistance to acute hypoxia; that a measure of the individual resistance of an animal to such hypoxia is Student's parameter for that animal; that the distribution of Student's parameter in a population is a lognormal distribution under any conditions; and that the number of animals with low resistance is always equal to the number of highly resistant animals. The procedure described makes it possible to limit the number of animals used in an experiment by recording with the requisite accuracy the proposed measures of resistance to acute hypoxia at the population and individual levels. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 9, pp. 239–241, September, 1995     

Inhibition of contractile activity of cultured rat cardiomyocytes in response to reduced oxygenation

Hypoxia completely abolishes the spontaneous contractile activity of cardiomyocytes. Once the original oxygenation is restored, the cells regain their functional activity, which exceeds the control level (particularly after a 2-h hypoxia). It can be assumed that the rapid restoration of cardiomyocyte functional activity is due to the preservation of a sufficiently high oxygen content and to the compensatory activation of glycolysis. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, N ^o 2, p. 215–217, February, 1995 Presented by I. P. Ashmarin, Member of the Russian Academy of Medical Sciences     

Effect of dexamethasone on the expression of binding sites for high-density lipoproteins in cultured rat hepatocytes (Independence of the hormone effect on the intracellular cholesterol pool)

It is shown that glucocorticoids play a key regulatory role directed toward the maintenance of an optimal level of binding and internalization of HDL₃ in hepatocytes. Their stimulatory effect on the expression of HDL receptors proves to be independent of changes in the CH content in parenchymal cells. Translated fromByulleten' Eksperimentalnoi Biologii i Meditsiny, Vol. 117, N ^o 1, pp. 50–53, January, 1994     

Accumulation of ATP by plasma membranes of human and rat hepatocytes induced by some growth factors and phosphatidylcholine

Using the method of ATP luminometry it is shown that crude membrane preparations from human and rat hepatocytes accumulate ATP 20–100 nmol/mg protein during a 1-min incubation under conditions of oxidative phosphorylation. Application of appropriate inhibitors shows that a possible contamination of the membrane preparations with mitochondria does not contribute to this ATP accumulation. Phosphatidylcholine, tumor necrosis factor, and cell proliferation factor markedly stimulate the accumulation of ATP by plasma membraneenriched particles isolated from rat and human liver. The hepatocyte plasma membrane is shown to be able to synthesize ATP from inorganic phosphate and ADP using the aerobic mechanism. ATP in the plasma membrane is assumed to participate in the transmembrane signal transduction from growth factors to the cell effector systems. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, N ^o 3, pp. 271–274, March, 1996 Presented by V. D. Fedorov, Member of the Russian Academy of Medical Sciences     

Morphofunctional aspects of liver regeneration in experimental correction of toxic hepatitis

It is demonstrated that cytoplasmic extract of rat pup liver stimulates cellular and intracellular regeneration of hepatocytes exposed to the toxic agent CCl₄. Injection of liver cytosol stabilizes lysosomal membranes, increases the coefficient of energy efficiency of mitochondria, and activates proliferation of polyploid hepatocytes. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, N ^o 6, pp. 656–659, June, 1995 Presented by D. S. Sarkisov, Member of the Russian Academy of Medical Sciences     

Protective effect of adaptation to hypoxia and its prolongation by pharmacological agents in rats prone to audiogenic epilepsy

Cytophotometric determination of RNA in various brain structures of hypoxia-adapted and unadapted epilepsy-prone rats at different times after an epileptic seizure shows much smaller decreases in RNA levels and their much more rapid return to normal in the adapted than in the unadapted rats. The adaptation to hypoxia produces a marked anticonvulsive effect, and this effect is enhanced and prolonged considerably by pharmacotherapy. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 117, N ^o 2, pp. 120–123, February, 1994     

Role of estrogens in the regulation of prolactin receptors in liver cells of female rats

Strong expression of prolactin receptors in sinusoidal domains and cytoplasmic granules of hepatocytes, which is independent of cell location in the hepatic lobule and is positively regulated by estrogens, is revealed in pubertal female rats. In estrogen-treated animals, Prolactin receptors are also exposed in the perinuclear space of some hepatocytes surrounding the central veins. Estrogens regulate the intensity of prolactin receptors expression in hepatocytes, but not the number of cells containing these receptors. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 9, pp. 264–267, September, 1994 Presented by I. P. Ashmarin, Member of the Russian Academy of Medical Sciences     

The use of a nonopiate leu-enkephalin analog and of hydra peptide morphogen for the correction of proliferation disturbances in tracheal epithelium and of LPO processes in lungs of newborn rats exposed to prenatal hypoxia

Newborn rats were born of females exposed to high-altitude hypoxia. Pregnant females were injected i.p. either nonopiate leu-enkephalin analog or hydra peptide morphogen 10 μg/kg 30 min prior to being placed in a pressure chamber. Prenatal hypoxia causes the inhibition of the proliferative processes in tracheal epithelium and activation of lipid peroxidation (LPO) in lungs of newborn rats. The administration of nonopiate leu-enkephalin analog prevents the development of posthypoxic alterations in newborn rats. The administration of hydra peptide morphogen inhibits the proliferation of tracheal epithelium and lowers the activity of the antioxidant defense of the lungs in newborn rats. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 117, N ^o 5, pp. 535–537, May, 1994 Presented by Yu. A. Romanov, Member of the Russian Academy of Medical Sciences     

Adaptation to hypoxia,unlike adaptation to stress,fails to protect the isolated heart from reperfusion after total ischemia (An NMR study)

Effects of adaptation to hypoxia on the contractility of isolated rat hearts and on their levels of ATP and inorganic phosphate after total ischemia were evaluated. This adaptation failed to render the cardiac energy-supplying system more resistant to postischemic reperfusion and thus did not accelerate the restoration of cardiac contractility after ischemia. The results of adaptation to hypoxia were then compared with those of adaptation to stress, which had been shown to bring about a marked increase in cardiac resistance to postischemic reperfusion. It is concluded that the profound differences noted between the cardioprotective effects of these two forms of adaptation are due to a much greater accumulation of stabilizing proteins from the HSP70 family during adaptation to stress. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 11, pp. 481–484, November, 1995 Presented by N. R. Paleev, Member of the Russian Academy of Medical Sciences