The Effect of Interval Hypoxic Training on the Psycho-physiological Status of Healthy Subjects

of the lecture on the 2nd International Conference "Hypoxia in Medicine" A number of studies have demonstrated that short term global and focal brain hypoxia in experimental animals has a clear protective effect and reduces the injury to the neurons in repeated ischemic exposure. (Kitagawa K. et al., 1991; Glazier S. et al., 1994; Matsushima K., Hakim A., 1995) . These phenomena were called "hypoxic preconditioning" and "ischemic tolerance" . It is believed that ischemic tolerance is based on the expression of biologically active compounds, displaying neuroprotective effect, and first of all it concerns the heat shock protein. Our ambition was to reproduce the phenomena of hypoxic preconditioning and of ischemic tolerance in brain cell culture, using the model of oxidative stress. In this we proceeded from the data indicating that one of the main pathogenetic factors causing neurons death in brain ischaemia, is free radical production and neuronal membranes lipid peroxidation (Siesjo B. et al., 1989; White B. et al, 1993) . Manylayer brain cortex cell cultures of 17-18 rats embryos after two weeks cultivation were exposed to 1-3 h hypoxia in the chamber with anaerobic gas mixture (N2 95%, CO2 5%; t= 36,5(C) in the absence of glucose . Such an exposure resulted in partial death of cells at the distanced terms of exposition. After hypoxic preconditioning culture was subjected to lipid peroxidation by iron-ascorobate system (20 (M FeSO4, 400 (M ascorbic acid in the balanced saline solution) . As a control we used cultures exposed to oxidative stress without hypoxic preconditioning. Hypoxic exposure caused suppression of the ascorbatedependent LPO in neuronal culture, reaching the peak already in the 2 h ischaemia. In this "antioxidant" effect persisted , gradually decreasing for not less than 4 hours after the cessation of the hypoxic exposure. The data obtained show that hypoxic preconditioning prevents injury and death of the neurons caused by the oxidative stress. Ehrehbourg I.V., Gorbatchenkov A.A.: INTERVAL HYPOXIC TRAINING OF PATIENTS WITH CORONARY HEART DISEASE Hyp. Med. J. 1993. V. 1. N 1. P. 14-16. A course of IHT was given to 24 patients with ischemic heart disease (IHD) associated with stable angina and with a past history of myocardial infarction. The patients underwent 15 to 25 daily sessions of IHT with the total duration of breathing the hypoxic mixture 20 to 60 min. The completion of the IHT course was marked by a lower incidence of anginal attacks, better physical stress tolerance and a 25.1-3.5% increase in the threshold capacity. The efficiency of respiration improved, the antiarrhythmic effect was manifest as well. IHT is recommended as a non-drug method of treatment and rehabilitation of IHD patients with associated stable angina of effort.. Ehrenbourg I.V., Kondrykinskaya I.I.: THE EFFICIENCY OF INTERVAL HYPOXIC TRAINING IN THERAPY OF CHRONIC OBSTRUCTIVE PULMONARY DISEASES Hyp. Med. J. 1993. V. 1. N 1. P. 17-18. A course of IHT was given to 118 patients with chronic obstructive pulmonary disease (COPD), chronic obstructive bronchitis (COB), infection-dependent form of bronchial asthma (IBA) and non-infectious bronchial asthma (NIBA). The IHT course was administered with the concomitant use of necessary broncholytics. The best clinical effect of IHT was noted in NIBA patients(improvement in 78% of cases). The clinical improvement in COB was observed in 88% and was accompanied by improvement in bronchial patency. In the IBA group the condition of 3 of 6 patients with severe steroid-dependent BA deteriorated. The clinical effect of IHT persisted an average of 4 months after treatment. The conclusion is made as to the positive effect of IHT primarily on NIBA and COB patients, the steroid-dependent form of BA being a relative counterindication for IHT. Emerson MR, Nelson SR, Samson FE, Pazdernik TL. A global hypoxia preconditioning model: neuroprotection against seizure-induced specific gravity changes (edema) and brain damage in rats. Brain Res Brain Res Protoc 1999 Dec;4(3):360-6 Hypoxia preconditioning states that a sublethal hypoxia episode will afford neuroprotection against a second challenge in the near future. We describe and discuss a procedure for the development of global hypoxia preconditioning in adult male Wistar rats, using a mildly hypoxic (9% O(2), 91% N(2)) atmospheric exposure of 8 h. The persistence of neuroprotection was analyzed using a kainic acid (KA) model of brain injury. Rats were challenged with KA (14 mg/kg, i.p.) on 1-14 days post-hypoxia. The effects of hypoxia preconditioning on seizure score, weight loss, brain edema and histopathology were assessed. Brain edema, predominantly of vasogenic origin, was measured 24 h after KA administration using a reproducible and quantitative method based on the specific gravities of tissue samples. A density gradient column (1.0250-1.0650 g/cm(3)) comprised of kerosene and bromobenzene was used to assess the presence of edema in regions involved in seizure initiation and propagation that are normally extensively damaged (i.e., piriform cortex and hippocampus). Specific gravities of tissues were calculated through extrapolation with known NaCl standards. We found that hypoxia preconditioning prevented the formation of edema in these brain regions when KA challenge was given 1, 3, and 7, but not 14 days post-hypoxia exposure. Furthermore, neuroprotection was observed in animals that had robust seizures. The described procedure may be used to examine the neuroprotective mechanisms induced by global hypoxia preconditioning against many subsequent challenges reflecting a variety of experimental models of brain injury, and will provide a better understanding of the brain response to hypoxia and stress. Fliss H., Comas T.M., Ehrenburg I.V., Gulyaeva N.V., Tkatchouk E.N.: EFFECTS OF IN VIVO HYPOXIC PRECONDITIONING ON TRANSCRIPTION FACTORS IN RAT HEART Hyp Med. J. 1997. V. 5. N 3. P. 9-10. We examined the possibility that the cardioprotective effects of in vivo hypoxic preconditioning achieved with intermittent hypoxia training (IHT) may be attributable to attenuation of the proinflammatory transcription factors (NF-kB, AP-1, Sp1). Male rats were subjected to 20 sessions of IHT of increasing duration and decreasing O2 content. Electrophoretic mobility shift assays with myocardial nuclear extracts showed a large decrease in the nuclear content of NF-kB, AP-1, and Sp1 in the hypoxic hearts. The data suggest that IHT cardioprotection may be caused by an increased antiinflammatory capacity and decreased susceptibility to stress in preconditioned hearts. Gulyaeva N.V., Stepanichev M.Yu.,Mitrokhina O.S., Moiseeva Yu.V., Onufriev M.V., Sergeev I.V., Lazareva N.A.,Tkatchouk E.N.: EFFECTS OF INTERVAL HYPOXIC TRAINING ON PARKINSONIAN SYNDROME MODEL IN RATS. 1.EFFECTS ON BEHAVIOR IN THE TOPEN FIELDL TEST Hyp. Med. 1996. V. 4. N 4. P. 7-11. Effects of interval hypoxic training on behavior in the Topen fieldL test was studied in rat model of Parkinsonian syndrome intranigral administration of 1methyl-4-phenyltetrahydropyridine (MPTP). MPTP administration resulted in behavioral disturbances characteristic for this model: decrease of locomotor (horizontal and vertical) activity, increase of freezing time and defecations number. IHT course carried out before neurotoxin administration prevented these behavioral disturbances. The results suggest that IHT provides for a stable physiological adaptation of dopaminergic system, of other systems of the brain and of the whole organism, this adaptation preventing the damaging effect of the neurotoxin. Gulyaeva N.V., Tkatchouk E.N.: ANTIOXIDATIVE EFFECTS OF INTERVAL HYPOXIC TRAINING Hyp. Med. J. 1997. V. 5. N 3. P. 18. Free radical homeostasis of the organism involves the reactions of active oxygen species generation (different systems producing superoxide, hydroxyl radicals, hydrogen peroxide, singlet oxygen, nitric oxide etc.) and the activity of enzymatic and non-enzymatic systems of free radical elimination. Disturbances of the steady state of free radicals increase in their generation and/or decrease in antiradical defense systems result in oxidative stress, a common step in the pathogenesis of different diseases. Acute hypoxia and especially subsequent reoxygenation induce excessive active oxygen species generation. Repeated moderate oxidative stress in hypoxiareoxygenation episodes is suggested to be an important factor of antiradical defense systems training in the course of interval hypoxic training (IHT). This suggestion is supported by the data obtained in Clinical Research Laboratory of "Hypoxia Medical Academy" in collaboration with Laboratory of Heart Patho-physiology, Institute of General Pathology and Patho-physiology RAMS, Moscow; Laboratory of Functional Biochemistry, Institute of Higher Nervous Activity and Neurophysiology RAS, Moscow; Maternity Hospital No. 2, Saratov. The data are presented demonstrating antioxidative effects of IHT both in animal experiments and in human studies. In rat brain, IHT resulted in an increase of superoxide dismutase activity and decrease in Fe/ascorbate induced lipid peroxidation. IHT suppressed different systems of free radical generation (including microsomal cytochrome P450 and nitric oxide synthase) in brain, lung and liver of rats. Beneficial changes in lipid peroxidation and antioxidative defense systems induced by IHT in normal animals are moderately expressed. Effects of IHT are much more pronounced in situations promoting oxidative stress. In a placebo-controlled experiment on rats, IHT was shown to prevent oxidative stress in striatum induced by intranigral administration of the dopaminergic neurotoxin MPTP (rat model of Parkinsonism). In a placebo-controlled study in pregnant women, IHT-induced decrease in active oxygen species generation in blood serum as well as increase in red blood cell superoxide dismutase activity were demonstrated. Moreover, antiperoxidative effects of IHT were revealed in umbilical blood serum and placenta where both free radical generation and lipid peroxidation were suppressed. IHT prevented increase in free radical generation in blood serum of pregnant women undergoing abdominal delivery in both pre-operational and early post-operational periods. This phenomenon indicates one of the mechanisms of preventive effect of IHT in operational stress. Thus, antioxidative effects of IHT include: a) decrease of active oxygen species generation; b) decrease in lipid peroxidation; c) increase in antiradical defense systems, and d) prevention of excessive free radical generation in conditions promoting oxidative stress. These effects represent an important mechanism of beneficial results of IHT in a wide spectrum of diseases and health-relating conditions. Kovalenko E.A., Tkatchouk E.N., Volkov N.I., Shaov M.T.: ACTIVIZATION OF ADAPTIVE MECHANISMS IN THE COURSE OF THE INTERVAL HYPOXIC TRAINING IN PATIENTS // Hyp. Med. J. 1993. V. 1. N 1. P. 8-9. The use of the principle of interval hypoxic training and adaptation to hypoxia under normobaric conditions appeared to be beneficial in the treatment of bronchial asthma, ischemic heart disease, autonomic vascular neuroses, neuralgia, peptic ulcer, moderate hypertension, reduction in stress-related conditions in the preand postoperative period. IHT mechanisms are considered, the importance of training enzymatic processes of the macroerg biological oxidation and resynthesis, the increase in the activity of the whole group of antioxidant enzymes, namely superoxide dismutase, glutathione reductase, glutathione peroxidase, catalase and the mechanisms of defense against free radicals are emphasized. Kotliarova L.A., Ehrenbourg I.V., Kondrykin-skaya I.I., Gorbatchenkov A.A.: INTERVAL HYPOXIC THERAPY IN COMPLEX TREATMENT OF RHEUMATOID ARTHRITS Hyp. Med. J. 1993. V. 1. N 1. P. 18. The IHT course was given to 10 patients with rheumatoid arthritis (RA) of 2 to 15 years duration. The course lasted 15-22 days. The dynamics of clinical and laboratory variables was assessed 3.5 weeks after IHT. IHT resulted in lesser duration of morning rigidity (from 199 to 15 min), active joints decreased in number (from 3.1 to 1.8), arthralgias disappeared or abated, the gait was normalized. 3-4 IHT sessions improved mood, sleep, appetite and physical activity. The daily intake of anti-inflammatory drugs was reduced. 3 patients did not show