Effect of hypoxia of increasing severity on the dynamics of cerebral cortex EEGs in rats with different resistance to acute oxygen deficiency

EEGs recorded from the cerebral cortex of rats with high and low resistance to hypoxia during “elevation” in a pressure chamber differ in the dynamics of the EEG power spectra. EEGs of highly resistant rats show phasic changes in biopotentials correlating with the severity of hypoxia: primary increase in the absolute power of all frequency ranges is followed by normalization and a secondary increase with predominance of the slow-wave component, inhibition of the β₂ range and the emergence of interhemispheric differences, and terminal inhibition of the power of all frequency ranges. In rats with low resistance to hypoxia, phases of relative normalization of EEG spectra and their depression during terminal period are not observed, all changes being represented by a continuous increase in the power of the α and δ ranges with progressive inhibition of the β₂ range and then of the β₁ range. Interhemispheric asymmetry is significant throughout the period of power increase. A high amplitude burst activity is recorded in rats of both types starting from an altitude of 8000 or 9000 m. The pattern of EEG changes in rats exposed to hypoxia of growing severity consistently reproduces those observed in patients with ischemic stroke. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 9, pp. 262–267, September, 1996     

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     

Role of ATP-sensitive K<Superscript>+</Superscript>-channels in antiarrhythmic and cardioprotective action of adaptation to intermittent hypobaric hypoxia

Mature Wistar rats were exposed to intermittent hypobaric hypoxia (5000 m, 6 h/day, 30 sessions). This mode of adaptation enhanced heart tolerance to the arrhythmogenic action of 45-min coronary occlusion, but does not affect the infarction size/risk area ratio. In some series, the rats were exposed to more severe intermittent hypobaric hypoxia (7000 m, 8 h/day, 6 weeks) followed by 20-min coronary occlusion and 3-h reperfusion one day after the last hypoxia session. In this case, adaptation reduced the infarction size/risk area ratio and enhanced cardiac tolerance to the arrhythmogenic effect of reperfusion, but had no effect on the incidence of ventricular arrhythmia during ischemia. We found that the cardioprotective and antiarrhythmic effects of adaptation to an altitude of 7000 m and the antiarrhythmic effect of 5000-m adaptation were mediated via activation of K_ATP channels. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 4, pp. 395–398, April, 2008     

Behavioral peculiarities and reactions of brain dopaminergic systems in rats with different resistance to acute hypobaric hypoxia

Locomotor activity in the open field test did not correlate with rat resistance to acute hypobaric hypoxia; there was a correlation between this resistance and rat behavior during acute stress. Immobility was characteristic of rats with low and particularly medium resistance to hypoxia; this reaction can be abolished by antidepressants. By contrast, highly resistant rats were mainly hyperactive. The resistance to hypoxia was associated with extreme parameters of dopaminergic neuron functioning. In low-resistant rats locomotor stereotypia was maximal, while perioral stereotypia was the minimal; highly resistant rats were characterized by an opposite pattern, and medium-resistant rats occupied an intermediate position. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 9, pp. 275–278, September, 2000     

Effect of semax heptapeptide on rat heart activity during acute hypobaric hypoxia in the early postnatal period

The effects of Semax heptapeptide on the resistance to acute hypobaric hypoxia and on hypoxic changes in the ECG chronotropic index were studied in 14- and 21-day-old pups. The resistance to hypoxia decreased with age. Hypoxic exposure caused bradycardia in both age groups. Semax reduced the bradycardiac reaction and exerted an antiarrhythmic effect without affecting the resistance to hypoxia. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 128, No. 8, pp. 161–164, August, 1999     

A comparative study of cholinergic systems of the neocortex and hippocampus in rats with low and high resistance to hypoxia

Synaptic structures in the neocortex and hippocampus of the intact brain were compared between rats with low and high resistance to hypobaric hypoxia. Activities of choline acetyltransferase, acetylcholinesterase, Na,K-ATPase, and the portion of protein in the light and heavy synaptosome fractions and subfractions were measured. A discrepancy in cholinergic metabolism molecular mechanisms between high and low resistance animals have been found in the heavy somatosoma fraction from the neocortex. Activities of choline acetyltransferase, acetylcholinesterase, and Na,K-ATPase in the synaptolemmal subfraction of low resistant rats were much lower than in high resistant rats. This implies a less effective synaptic transmission in proper cholinergic neurons in the low resistance animals and, therefore, specifically changed neuron functioning in the circulation control. No differences in the cholinergic components of either neocortical light synaptosome fraction or hippocampal light and heavy synaptosome fractions were found between low and high resistance rats. Translated fromByulleten' Eksperimental'noi Biologii I Meditsiny, Vol. 125, No. 5, pp. 521–525, May, 1998     

Protective effects of trimetazidine in acute hypoxia

Trimetazidine improves resistance to acute hypobaric hypoxia. Intraperitoneal injection of this preparation in an optimal protective dose (25 mg/kg) to rats prevents serious disturbances of energy metabolism and activation of lipid peroxidation in the brain, heart, and liver. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 125, No. 4, pp. 410–412, April, 1998     

New property of the heparin-serotonin complex

The antihypoxic activity of the heparin-serotonin complex was studied under conditions of acute hypobaric hypoxia. Rats were given an intraperitoneal injection of the complex in a dose of 300 μg/kg and “lifted” on a height of 12,000 m. In these rats, the intervals before the posture loss and the second agonal inhalation were 9.6- and 8.8-fold as long as those in control rats. The survival of the complex-treated rats was 90%, 70% in rats injected with heparin or serotonin, and 50% in the control group. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 10. pp. 425–427, October, 1998     

Role of glycolysis in the maintenance of the energy-synthesizing function of hepatocytes from rats adapted and nonadapted to hypoxia at different oxygen concentrations

It is demonstrated that the lactate-Po₂ dependence is the same in hepatocytes of rats with high and low resistance to hypoxia and does not correlate with phasic changes in the ATP concentration in the 890–50 μM O₂ region. Strong activation of lactate formation against the background of ATP decrease indicates that glycolysis is not the major mechanism determining the steady-state ATP level in the cell and affecting the ATP-Po₂ relationship in a wide range of oxygen concentrations. The intensity of glycolysis in hepatocytes of rats with high resistance to hypoxia is markedly increased after periodic adaptation to hypoxia but remains practically unchanged in the hepatocytes of low-resistance rats. This indicates that fundamentally different compensatory mechanisms are involved in this process in the liver of high- and low-resistance rats. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, N ^o 1, pp. 28–32, January, 1995     

Effects of carotid glomectomy on erythron parameters in rats differing in the resistance to acute hypoxia

Rats with low resistance to acute altitude hypoxia did not differ from those with high resistance in the erythron parameters recorded under normal environmental conditions. After a bilateral carotid glomectomy, significant falls in the red blood cell count, hemoglobin concentration, packed cell volume, and mean corpuscular hemoglobin were recorded only in the group with low resistance to acute hypoxia, although the “altitude” resistance was decreased to similar degrees in the two groups. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 7, pp. 12–13, July, 1996     

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     

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     

Effect of melatonin on cyclic nucleotide content and intensity of lipid peroxidation in the hippocampus and habenula of rats exposed to acute hypoxia

Single intraperitoneal injection of melatonin in a dose of 1 mg/kg prevented accumulation of cGMP and intensification of lipid peroxidation in the hippocampus and habenula of rats exposed to acute hypobaric hypoxia (12,000 m). Changes in habenular content of cGMP suggest that melatonin prevents hypoxia-induced activation of heme-oxygenase. Translated fromByulleten' Eksperimental" noi Biologii i Meditsiny, Vol. 130, No. 8, pp. 168–171, August, 2000     

Changes in hypoxia resistance in rats during daytime

The resistance to acute hypoxia in male Wistar rats was evaluated by the period of survival after exposure to high-altitude hypoxia (11.5 km above see level). The study was performed during daytime (13.00–21.00) in autumn. The fatal rat population was characterized by the log-normal distribution of survival periods. The rats with low and moderate resistance to hypoxia exhibited similar diurnal variations in it with gradual decrease by the end of daytime more pronounced in low-resistant rats. The rats with high resistance showed relatively constant resistance to hypoxia which decreased only at 21:00. All groups revealed a relatively stable resistance to hypoxia from 16:00 to 18:00. These variations in the resistance to hypoxia should be taken into consideration when planning experimental research. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 3, pp. 256–260, March 1999     

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     

Impaired plasticity of hippocampal synaptic transmission in rats exposed to prenatal hypoxia is normalized by treatment with nootropic dipeptides

Experiments on hippocampal slices from young rats exposed to hypobaric hypoxia duringin utero development revealed enhanced responsiveness (an increase in a CA1 field response amplitude) and reduced plasticity (a low incidence of field response long-term potentation following high-frequency stimulation) of CA1 pyramidal neurons. Postnatal treatment of animals with piracetam peptide analogs constructed on the basis of pyroglutamate and proline normalized both these physiological indices. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 12, pp. 592–595, December, 1995 Presented by G. N. Kryzhanovskii, Member of the Russian Academy of Medical Sciences     

Effect of acute hypoxia on resistance to hypoxia in rats

The resistance of rats to hypoxia was measured by survival time after exposure to high-altitude (11.5 km) hypoxia. The first exposure to acute hypoxia caused phasic changes in the survival time: short-term in high-resistant rats (about 24 h) and long-term in moderate- and lowresistant rats (38–39 days) starting from 1 h and 6–7 days after the first exposure, respectively. Adaptive reactions were more pronounced in low- and moderate-resistant rats, while disadaptation was typical of high-resistant animals. In all rats, the adaptive effect dominated until days 22–23. Throughout the testing, the initial type of resistance was retained in 79% of high-resistant rats, in 41% of low-resistant and in 33% of moderate-resistant rats, i. e., the initially homogenous groups formed after the first exposure in accordance with the type of resistance became mixed, which reduced the intergroup differences. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 6, pp. 625–628, June, 1999     

Energizing and antihypoxic effects of energostim

It is demonstrated that energostim, an aqueous mixture of NAD⁺, cytochromec, and inosine possesses pronounced antihypoxic activity. Energostim increases by 26-fold the survival rate of rats with low resistance to hypoxia under conditions of hypobaric hypoxia. Administration of energostim before the “rise” in a pressure chamber prevents a decrease in the brain content of ATP in rats with high resistance to hypoxia under the conditions of maximum hypoxia and increases it in rats with low resistance to hypoxia. Energostim has no effect on the survival rate of high-resistant rats in acute hypobaric hypoxia and on the brain content of macroergic substances in low- and high-resistant rats when agony is not developed on “the critical height” and there is no deficiency of macroergic substances. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 123, No. 6, pp. 659–662, June, 1997     

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     

Effects of Preconditioning on the Resistance to Acute Hypobaric Hypoxia and Their Correction with Selective Antagonists of Nicotinic Receptors

Hypobaric hypoxic preconditioning increased the resistance of low resistant and highly resistant rats to acute hypobaric hypoxia at a critical height. Intergroup differences in the resistance of rats to acute hypobaric hypoxia were not observed after hypobaric hypoxia and one variational series with a wide range of resistance (4.5-24.5 min) appeared. Methyllycaconitine, an antagonist of subtype α₇ nicotinic cholinergic receptors, abolished the influence of hypobaric hypoxia on low resistant rats, but had no effect on highly resistant animals. Mecamylamine, a preferential antagonist of subtype α₄β₂ and α₃-containing cholinergic receptors, did not modulate the effect of hypobaric hypoxia. By contrast, hypobaric hypoxia abolished the effect of mecamylamine on the resistance of rats that were not trained under conditions of hypobaric hypoxia (low resistant and highly resistant animals with low sensitivity to hypobaric hypoxia). We conclude that the same effect of hypobaric hypoxia is mediated by various mechanisms, which involve different nicotinic cholinergic receptors. They differ from the resistance mechanisms in non-trained rats.