Vol 14, No 1 (2016)


From the S.P. Botkin’s idea of “preexposure” to preconditioning phenomenon. Perspectives for use of phenomena of ischemic and pharmacological preconditioning

Zarubina I.V., Shabanov P.D.


The phenomenon of ischemic preconditioning based on the S.P. Botkin’s idea about defense effect of disturbing factors acting in small intensities is observed in the review. The modern literature data about main types of preconditioning exposure, triggers and mechanisms of ischemic preconditioning are reviewed. This phenomenon was supported in many experiments in vivo and in vitro on animals of different spices as well as in humans in clinical conditions. Ischemic preconditioning is qualified as transient positive changes in the organs and tissues produced by activation of rapid endogenous adoptive processes in them during the short period of subletal ischemia and reperfusion and which defend them from subsequent ischemic episodes. There are early and late ischemic preconditioning (the second window of defense). The first type of ischemic preconditioning belongs to classic type of preconditioning and is produced by the short ischemic episodes (3-5 min) and similar intervals of reperfusion. Ischemic preconditioning observed in a day or more after preconditioning stimuli is named as late preconditioning with genes expression, synthesis of heat shock proteins (HSP 72 in particular) and NO synthase as the basis mechanisms underlying of it. Administration of triggers like adenosine, forbol ether, bradykinine or glycerol derivatives into the blood or ischemic tissues produces defense action similar to ischemic preconditioning and qualified as pharmacological preconditioning. Preconditioning induced by pharmacological agents are more preference than short ischemic episodes. Antihypoxic effects of benzimidazol derivatives in both an acute hypoxia and hypoxic preconditioning are described in the article. Other perspectives of pharmacological preconditioning in practical use are also discussed.
Reviews on Clinical Pharmacology and Drug Therapy. 2016;14(1):4-28
pages 4-28 views

The mitochondrial ATP-dependent potassium channel and its pharmacological modulators

Pogilova E.V., Novikov V.E., Levchenkova O.S.


This review is devoted to analysis of current research about the role of mitochondrial ATP-dependent potassium channel (mitoКАТP) in the regulation of metabolic processes of the cell. The mechanisms of cell adaptation to hypoxia and ischemia involving mitoКАТP is considered in the article. The opportunity of pharmacological modulation of mitoКАТP activity to stimulate processes of cell adaptation to damaging factors is discussed. This approach seems promising for the development of effective pharmacotherapy of diseases which have in their pathogenesis the state of hypoxia and ischemia.
Reviews on Clinical Pharmacology and Drug Therapy. 2016;14(1):29-36
pages 29-36 views

Acute hypoxia influence on cardio-respiratory system and new possibilities of pharmacological prophylactics of hypoxia in experiment

Evseev A.V., Pravdivtsev V.A., Sosin D.V., Yevseyeva M.A.


Cardiorespiratory system activities have been studied on rats in experiment after oral introduction of the new selenium-containing metal-complex substance πQ1983 in dose 100 mg/kg before and under action of acute hypercapnic hypoxia (AH + Hc). The substance was introduced 90 min. before (incubation period) placement of animals into hypoxic chambers with 1.0 L free volume. During each experiment as well as during AH+Hc an electrical activity of myocardium (ECG) and respiration curves called pneumobarogramm (PBG) were recorded simultaneously. It has been established that the substance πQ1983 made cardiodepressive effect and decreases parameters of lungs ventilation in animals. According to ECG and PBG dynamics, rats protected by the substance demonstrated a high resistance level to the aroused acute hypoxia with hypercapnia, that expressed by weakening of early reactions from cardiorespiratory system under hypercapnia action, and by twice longer life span of animals in hypoxic experiment.
Reviews on Clinical Pharmacology and Drug Therapy. 2016;14(1):37-45
pages 37-45 views

Tissue specific peculiarities of vibration-induced hypoxia of the rabbit heart, liver and kidney

Vorobieva V.V., Shabanov P.D.


The purpose of the paper was experimental study of activity of energy production of the heart, liver and kidney after harmful action of general vibration with 8 and 44 Hz frequency. The functional state of native mitochondria in tissue homogenates was studied by polarographic method by means of closed oxygen device of halvanic type in thermostated cuvette of 1 ml volume in the salt medium of incubation. Metabolic states of mitochondria of the rabbit heart, liver and kidney were modeled in vitro in oxidation of endogenous substrates (before and after administration of inhibitors of different stages of breath chain) varying exogenous substrates (before and after administration of 2.4-DNP into the cell). In order to synchronize the changes in short time, the incomplete cycle of metabolic states “endogenous breath → rest → activity” was used. The velocity of mitochondrial oxidation of endogenous substrates was determined by tissue type, and was 16.3 ± 4.3, 5.2 ± 0.6 and 8.13 ± 1.4 ng-atom О min-1mg-1 protein for the heart, liver and kidney of intact animals respectively. In the heart, after high frequent vibration, the reduction of oxidation velocity of NAD-dependent substrates in rest and in active metabolic state of mitochondria was 43 % (р ≤ 0.05) and 30 % (р ≤ 0.01) respectively, while the velocity of oxidation for endogenous succinic acid increased by 77 % (р ≤ 0.05) to 21st session of vibration, then constantly decreasing to the end of vibration sessions. The same changes but in less degree were registerted in the liver and kidney. The systems of energy production of the heart and the studied parenchimatic organs were involved in reaction on vibration exposure and reacted typically by low energetic shift with hyperactivation of endogenous succinic acid system of oxidation and inhibition of NAD-depended part of the breath chain of mitochondria. Therefore, the study of bioenergetics mechanisms of hypoxia in different tissues allows to clear the molecular targets for pharmacological action by means of substrate antihypoxants.
Reviews on Clinical Pharmacology and Drug Therapy. 2016;14(1):46-62
pages 46-62 views

The role of hypoxia in stroke and convulsive states. Antihypoxants

Voronina T.A.


The review deals with the main types of hypoxia and the reasons leading to its development, discusses the development of mechanisms of hypoxiа. Particular attention is paid to brain hypoxia and its role in the development of strokes and convulsive states. The features of the application of antihypoxants and antioxidants at different hypoxic conditions including stroke and seizures are discussed.
Reviews on Clinical Pharmacology and Drug Therapy. 2016;14(1):63-70
pages 63-70 views

Influence of different hypoxia types on p-glycoprotein functional activity and expression

Yakusheva E.N., Chernykh I.V., Shulkin A.V., Popova N.M.


The review of literature is devoted to researches in vitro and in vivo in which functioning changes P-glycoprotein (Pgp) under the influence of hypoxia of different types are shown. In the majority of scientific works activation of expression and functional activity of Pgp is shown that authors connect with activation of HIF-1 and Sp1 which are described in more detail. However a number of researches disproves the conclusion about induction of activity of Pgp in the conditions of hypoxia that testifies about difficult mechanisms involved in regulation of Pgp activity, their dependence on a type and duration of hypoxia, redox status and other parameters.
Reviews on Clinical Pharmacology and Drug Therapy. 2016;14(1):71-77
pages 71-77 views

Nitric oxide and hypoxia at adaptation to muscular work (brief review)

Radchenko A.S.


The The last two decades there has been a growing interest in the nitric oxide (NO) function in the body of a healthy person. In the study, two very specific problems are discussed: a) the NO involvement in mechanisms of adaptation at muscular work under hypoxia conditions, and b) the inorganic nitrate supplementation in athlete’s diet with the aim of sports performance improvement. The reorganizations that occur in the heart vasculature and in skeletal muscle for providing muscle work under hypoxia conditions examined. The named problems are particularly relevant in contemporary sports in which the adding of hypoxic exposure on a body of training persons as well as the inorganic nitrate in sports nutrition application as added means to special performance improvement. Raise the problem of the hypoxia and inorganic nitrate mutual exploitation in the training process.
Reviews on Clinical Pharmacology and Drug Therapy. 2016;14(1):78-88
pages 78-88 views

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