Antihypoxic effect of glucosamine in acute hypoxic states in mice]

The preventive glucosamine injection causes an increase in the survival of mice with acute hypobaric hypoxia. The injection of glucosamine, combined with sodium hydroxybutyrate greatly increased their antihypoxic activities.     

NO-dependent mechanisms of adaptation to hypoxia.

In studying NO-dependent mechanisms of resistance to hypoxia, it was shown that (1) acute hypoxia induces NO overproduction in brain and leaves unaffected NO production in liver of rats; (2) adaptation to hypoxia decreases NO production in liver and brain; and (3) adaptation to hypoxia prevents NO overproduction in brain and potentiates NO synthesis in liver in acute hypoxia. Dinitrosyl iron complex (DNIC, 200 microg/kg, single dose, iv), a NO donor, decreases the resistance of animals to acute hypoxia by 30%. Nomega-nitro-L-arginine (L-NNA, 50 mg/kg, single dose, ip), a NO synthase inhibitor, and diethyl dithiocarbamate (DETC, 200 mg/kg, single dose, iv), a NO trap, increases this parameter 1.3 and 2 times, respectively. Adaptation to hypoxia developed against a background of accumulation of heat shock protein HSP70 in liver and brain. A course of DNIC reproduced the antihypoxic effect of adaptation. A course of L-NNA during adaptation hampered both accumulation of HSP70 and development of the antihypoxic effect. Therefore, NO and the NO-dependent activation of HSP70 synthesis play important roles in adaptation to hypoxia.     

Acute adaptation of mice to hypoxic hypoxia.

Tolerance to hypoxia in vivo and in vitro was significantly increased by acute and repetitive exposure of mice to autoprogressive hypoxia. The average tolerance times of the successive 2nd, 3rd, 4th and 5th runs of exposure were, respectively, 2, 4, 6 and 8 times as long as that of the first exposure. The survival times under hypobaric chamber and cyanide toxification in the 4th exposure were, respectively, 10 (and even as much as 86) and 4 times those in control mice without exposure to hypoxia. Mandibular respiration and spinal reflex in vitro in hypoxia-resistant animals lasted 5-6 times as long as in control animals not previously exposed to hypoxia. Animals that received brain homogenate from hypoxia-resistant mice remained alive in a hypobaric chamber 2 times as long as those that received homogenate from controls and those that received saline. These results indicate that a kind of quickly developing adaptation with increased tolerance is achieved by acute and repetitive exposure of mice to progressive autohypoxia and some plastic or adaptive changes occur in the brain of hypoxia-resistant animals, including the production of some kind of water-soluble antihypoxic factors.     

Redistribution of myocardial blood flow in chronic ischemia under the effects of pharmacological agents

In the experiments with anesthetized dogs under chronic myocardial ischemia the effect of propranolol, diltiazem, lithium and sodium hydroxybutyrate on the myocardial blood flow redistribution was studied with the help of ultrasonic method. The redistribution was estimated by the ratio change of blood flows in veins which drain blood directly from the focus of myocardial ischemia and total myocardial of left ventricular (v cardiac magna). It was established that propranolol increases the ratio and diltiazem decreases it. Some differences in the effect of antihypoxic drugs were revealed. Sodium hydroxybutyrate redistributed the blood flow in favour of the focus of myocardial ischemia and lithium hydroxybutyrate increased the blood flow both in the focus of myocardial ischemia and in the conditionally-intact region of myocardium of left ventricular.     

Antihypoxic and antioxidative properties of bemitil

The authors discovered antihypoxic properties of the bemitil (pretreatment injections 50 mg/kg intraperitoneally) in the experiments on rats with the circulatory or hypoxic hypoxia. There was limitation of pO decrease and diene conjugates and Schiff bases production increase with the drug in the circulatory hypoxia conditions. Bemitil restricted malondialdehyde accumulation in the rat brain homogenate under the activation of free radicals processes. In the mitochondrial suspension incubation similar effect of the medicine was accompanied with limitation of organelle degradation. Bemitil showed no antiradical activity.     

Protective effect of lithium oxybutyrate on the ischemic myocardium

In the experiments on different animal species (mice, cats, dogs) lithium hydroxybutyrate has been shown to have antihypoxic and anti-ischemic effects. Lithium hydroxybutyrate improved the functional state of the ischemic myocardium, stimulated the accumulation of macroergic phosphates (ATP) in the heart, protected the ischemic myocardium and delayed the progression of the reversible ischemic damage into the irreversible one. The improvement of the collateral coronary circulation plays an important role in the anti-ischemic action of the drug.     

Effect of apressin, obsidan, diprazine and their combination on the concentration of NAD and NADH2 in the liver and brain of hypoxic rats]

Apressin (2.5 mg/kg), obsidan (10 mg/kg), and diprazine (10mg/kg) caused an increase in the content of NAD + NAD.H2, without affecting their ratio, in the liver and brain of intact animals. These drugs, taken in the same doses, especially when used together, caused an increase in the NAD + NAD.H2 level; as to NAD/NAD.H2 ratio--it decreased in the state of hypoxia. The authors believe the antihypoxic action of apressin, obsidan, and diprazine to be connected with the rise in the total nicotinamide adenine denucleotide content and with increase of its oxidized form.     

Antihypoxic properties of endorphins, enkephalins and their analogs

The models of hypoxic hypoxia have been created in the experiments on mice by two ways: placing them into hermetic chamber or "lifting" them to 10.500-10.700 metres in the altitude chamber. The influence of enkephalins and their 12 analogs on the resistance of mice to hypoxia was tested. Enkephalin analogs with antihypoxic activities were detected using both models. It was shown that the mechanism of antihypoxic influence of opioids involves stimulation of their mu- and sigma-receptors and that other neurochemical systems of the body also take part in the realization of antihypoxic effects of the peptides. It is suggested that leu-enkephalin and des-tyr1-gamma-endorphin play, most likely, a role of endogenous antihypoxic agents.     

Experimental study of the antihypoxic properties of ibuprofen and other nonsteroidal anti-inflammatory preparations

The antihypoxic properties of ibuprofen, diclofenac sodium, acetylsalicylic acid and phenylbutazone have been studied. Ibuprofen significantly increases survival of mice in the model of hypoxic hypoxia with hypercapnia. In addition, ibuprofen and diclofenac sodium possess antihypoxic protective activity in the models of circulatory and anoxic hypoxia in rats.     

Protective effect of adrenergic alpha 2-receptor agonists in hypoxic hypoxia

The antihypoxic effect of alpha 2-adrenoceptor agonists was studied by two different approaches: reproduction of the effect by a number of alpha 2-agonists and its blockade with selective antagonists. The data obtained suggest that alpha 2-adrenoceptor agonists increase the survival and the lifespan of mice in all the models of acute hypoxic hypoxia under study. A close correlation between antihypoxic action of alpha 2-adrenoceptor agonists and their anticalorigenic effect was established (r = +0.87; P less than 0.01).     

Radiation protection of mice with hypoxic gas mixtures after administration of anti-hypoxic agents

It is shown that such substances as gutimine, antizol and mexamine increases the resistance of animals to short-term breathing of gas mixtures containing 6 and 5% oxygen. Even if some of them decrease the degree of radioprotective effect of hypoxia, they afford the possibility to safe use of breathing mixtures with lower oxygen content than endured by intact animals, with the resulting increase in radioprotection. Thus the antihypoxic substances can be tested during hypoxiradiotherapy of human tumors.     

Effect of the antihypoxic agent ionol on the morphofunctional state of the air-blood barrier of the lungs in hypoxic anoxia

It is shown that antihypoxic ionol has promoted normalization of the air-blood lung barrier ultrastructure, activation of the surfactant system under acute hypoxic hypoxia effect as well as compensatory redistribution of the thickness of separate barrier layers due to intensified synthesis of phospholipids which are the components of cytoplasmic membranes and pulmonary surfactant.     

Delayed antihypoxic effect of leu enkephalin in mice

Hypobaric hypoxic hypoxia conditions were simulated by raising mice in the altitude chamber to the level of 10,500-10,700 m. Enkephalin, its analogues, morphine and naloxone were injected once 1, 2, 3, 6 and 14 days prior to the experiment, and then their effects on stability to hypoxia were investigated depending on the time of drug administration. Only leu-enkephalin after a single injection was found to have antihypoxic properties for a week. Naloxone, but not phentolamine hydrochloride, blocked delayed antihypoxic effect of penta-peptide. Leu-enkephalin is thought to be endogenous antihypoxant.     

The evaluation of the efficacy of antihypoxic agents lowering hemoglobin oxygen affinity in acute cerebral ischemia]

Influence of natrii hydroxybutyrate (100 mg/kg), ascorbate (100 mg/kg), cavinton (5 mg/kg), bemitil (50 mg/kg), ethomersol (50 mg/kg) on Hb-O2 affinity and cortex PO2 after both carotid artery occlusion in rats was investigated. Correlation (r-0.87; P less than 0.05) between lowering of Hb-O2 affinity and antihypoxic effect was demonstrated in the line of these drugs.     

Effect of melatonin and epithalamin on activity of marker enzymes in the cell membrane in the forebrain of rats under acute hypoxia

The effects of a single-shot intraperitoneally administration of melatonin in a dose of 1 mg per kg body weight and epithalamin in a dose of 2.5 mg per kg body weight on the activities of Na+, K(+)-ATPase and 5'-nucleotidase were investigated in the forebrain of juvenile male white rats under the acute hypobaric hypoxia. The melatonin and epithalamin administration against the background of acute hypoxia prevented an acute hypoxia inducing decrease in the activity of Na+, K(+)-ATPase as well as increased in the activity of 5'-nucleotidase. Such effects of pineal hormones can promote antihypoxic protection of neurons.     

Antihypoxic effect of vitamin E and its derivative in rats under modeling of hypoxic conditions of different origin

The increase of ubiquinone content in myocardial mitochondria and succinateubiquinone reductase activity in rat blood leucocytes under hypoxic hypoxia and acute microfocal myocardial damage [table: see text] have been shown. At the same time the succinateubiquinone reductase activity of rat myocardial mitochondria do not change substantially. We simultaneously observe the dramatic drop in NADH-ubiquinone reductase activity under experimental myocarditis. This fact demonstrates higher stability of succinateubiquinone reductase system and differences in metabolical processes under hypoxic conditions of different origin. All vitamin E derivatives studied demonstrate substantial antihypoxic activity, which is connected with increased animals' survivability, ubiquinone content in myocardial mitochondria and stabilization and leveling of succinateubiquinone reducatse activity in rat blood leucocytes. alpha-Tocopherolacetate with shortened to six carbon atoms side chain is the most effective in this respect. We discuss possible mechanisms for the realization of vitamin E and its active derivative's antihypoxic effect.     

Effect of drugs on the resistance of the myocardium to hypoxia

A method for the investigation of drug effects in the myocardium resistance to hypoxia has been suggested. It is based on the determination of drug effects on the performance of the isolated spontaneously contracting atrium (ISCA) of rats under hypoxic conditions. Hypoxia was induced by oxygen displacement from the nutritional solution by nitrogen. ISCA resistance to hypoxia was assessed by the mechanogram of the heart preparation (the duration and volume of ISCA performance being up to 50% of the initial amplitude). Using the inhibitor analysis, it has been demonstrated that the given model of myocardial hypoxia adequately reflects the role of energy cellular metabolism in the regulation of ISCA resistance to hypoxia and can be used in the search for myocardial antihypoxic agents.     

The significance of the mu- and delta-opiate receptors in realizing enkephalin action on the course of hypoxic hypoxia]

New enkephalins analogues have been synthesized. They are characterized by linear, cyclic and branched peptide chain. A relationship has been established between antihypoxic activity of opioid peptides an their interaction with opiate receptors. Compounds efficiently interacting with mu-receptors irrespective of delta-receptors affinity, promote longer survival of mice in hypoxia. The antihypoxic effect of opioids is proportional to their specificity to mu-receptors.     

Effect of hypoxia on DNA fragmentation in different brain regions of the newborn piglet

DNA fragmentation has been studied in different regions of the newborn piglet brain following different times of normobaric hypoxia (5% O(2), 95% N(2)). After 1 hr of hypoxia, fragmented DNA was observed in cerebellum, cortex, hippocampus, and striatum but not in hypothalamus. More fragmentation occurred in these areas of the brain when the animals were kept under hypoxia for times up to 8 hr 45 min. When the animals were submitted to hypoxia for two and a half hours, integrity of DNA was recovered respectively after 3 hr of exposure to the ambient atmosphere in hippocampus and striatum, but 4 hr of recovery were necessary for cerebellum and cortex. These results are discussed in terms of the consequences of neonatal hypoxia and apnea for newborn infants and economical impact for farm animals.     

The short-term and long-lasting changes in DNA and RNA synthesis in the cerebral cortex cells of animals subjected to hypoxia and nerve tissue transplantation]

The DNA and RNA synthesis in the cells of the brain cortex of intact rats and animals subjected to hypoxia, hypoxia with subsequent transplantation or by the local brain injury has been investigated. The DNA synthesis changes insignificantly in the case of hypoxia, it enhances slightly in the area of the injury and increases much more after transplantation. The RNA synthesis decreases considerably immediately after hypoxia and decreases much more 120 days later. Using the ultracentrifuge method it has been found that under the effect of hypoxia the number of nervous cells decreases, the number of glial cells does not change. The local injury in the nervous tissue enhances abruptly the synthesis in neurons and glial cells in the hypoxia-exposed animals, the embryonic nervous tissue transplantation normalizes the number of neurons in the specimens under study and the RNA synthesis in the neurons and glial cells.