Bioenergetic hypoxia is defined as a phasic process starting at the substrate site of the respiratory chain with injury to the mitochondrial enzymatic complex I and involving, as oxygen insufficiency progresses, the terminal cytochrome site of the respiratory chain. Different stages of the process, determined experimentally, are described from a bioenergetic viewpoint. The development of bioenergetic hypoxia in tissues of aninlals with different resistance to hypoxia is analyzed. Modern concepts of the trigger mechanisms of bioenergetic hypoxia and approaches to correcting the function of the energy system at different stages of hypoxia are discussed.
Key Words: bioenergetic hypoxia; energy metabolism; respiratory enzymatic complexes; individual sensitivity to hypoxia; adaptation; antihypoxantsHypoxia is a highly prevalent phenomenon, which develops both under conditions of oxygen deficiency in the environment and as a result of a variety of diseases involving the respiratory and cardiovascular systems and impairing blood transporting function. All such disorders lead to a decrease in oxygen delivery to tissues to a level which is insufficient for maintaining function, metabolism, and structure of the cell. Thus, hypoxia is an important problem of practical and theoretical medicine.This problem has been researched for more than a hundred years. In Russia it attracted the attention of I. M. Sechenov, V. V. Pashutin, P. M. Al'bitskii, and E. A. Kartashevskii. Later it became the main object of research for N. N. Sirotinin, A. M. Charnyi, I. R. Petrov, Z. I. Barbashova, M. N. Gaevskaya, and lnany others. Due to these investigations, stndy of hypoxic states became an important branch of fundamental and applied medicine, which still remains a priority trend for the Russian science. At Department of Bioenergetics, Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow present, a vast data bank on the mechanisms of hypoxia has been accumulated, permitting the creation of classifications of hypoxic states, development of prognostic criteria for assessing them, and analysis of the succession of disorders occurring under conditions Of oxygen deficiency.The intricate time course of this process and involvement of a wide spectrum of functional and metabolic systems regulating it at different levels of organization determine the multiplicity of the limiting sites and mechanisms underlying hypoxia. This l~act explains why, despite an almost lO0-year history of investigation, many pathogenetic aspects of hypoxia and many questions in antihypoxic defense are still not solved.The crucial factor leading to the development of h3rpoxic states is oxygen delivery from tile environment to the cell, where it participates ha reactions of aerobic energy production as the substrate of cytochrome oxidase (CCO) --the terminal exlzyme of the mitochondrial respiratory system. That is why oxygen deficiency under some conditions can limit or completely suppress aerobic energy production. The levels