Single exposure to moderate (10% O(2)) hypobaric, normobaric, and intermittent hypoxia is followed by a preconditioning response of the organism. The mechanisms for immediate adaptation are activated during the hypoxic period. Intermittent reoxygenation not only delays, but even suppresses this process. However, periods of oxygenation during the course of hypoxic training reduce the effect of hypoxia and prevent the possibility for "overdosage" of the adverse stimulus. Hence, they have a regulatory or normalizing role under these conditions. Our results indicate that hypoxitherapy in intermittent hypoxia mode provides optimum conditions for long-term adaptation.

We studied the effect of intermittent normobaric hypoxia on the formation of adaptive signs and state of mitochondrial enzymes in the cerebral cortex of rats with different resistance to hypoxia. Kinetic parameters for mitochondrial enzymes in the substrate region of the respiratory chain of the cerebral cortex underwent various changes in low resistant and highly resistant rats over the first 2 h after 1-h intermittent normobaric hypoxia. Low resistant animals were characterized by more effective functioning of rotenone-sensitive NADH-cytochrome C reductase and succinate-cytochrome C reductase under conditions of increased reduction status of the cell. These features correlated with the increase in the general resistance of animals. Significant changes in kinetic properties of mitochondrial enzymes and signs of the development of resistance were not found in highly resistant rats. Reciprocal relations between mitochondrial enzyme complexes in the substrate region of the respiratory chain probably play a role of the signal regulatory mechanism, which mediates tissue-specific and general resistance of rats under conditions of intermittent normobaric hypoxia. These effects did not depend on oxygenation of the inhaled gas mixture during the inter-hypoxic period.

Succinate-containing derivatives of 3-hydroxypyridine, mexidol and proxypin, serve as succinate donors for the respiratory chain and contribute to activation of the succinate oxidase pathway of oxidation. Under conditions of hypoxia, these changes promote recovery of aerobic energy production, normalization of intracellular ATP concentration, and development of the antihypoxic effect. Succinate-free analogues of the test compounds exhibit no such properties. Both agents are considered as energotropic substances. The specific effect of these compounds is manifested in direct interaction with the respiratory chain and normalization of ATP synthesis under conditions of hypoxia/ischemia. The test compounds can be used for the correction of energy metabolism disorders during acute oxygen deficiency. Moreover, they can be used for the treatment of associated functional disturbances.

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There are tissue-specific and phenotypic differences in the basal levels of HIF-1α under normoxic conditions. Induction of short-term adaptation to hypoxia and formation of long-term adaptation are genetically determined. These phenomena are observed only in animals with low resistance to hypoxia and are associated with biphasic expression of HIF-1α in the neocortex only during hypoxic preconditioning. Severe hypoxia disorders HIF-1α expression and impairs the formation of short-term and long-term resistance. In animals with high resistance to hypoxia, neither short-term nor long-term resistance develops in response to hypoxic exposure, and this correlates with the absence of changes in post-hypoxic HIF-1α levels in the neocortex.