Hypercapnia and Hypoxia Stimulate Proliferation of Astrocytes and Neurons In Vitro.

We compared proliferative activity and hypoxic tolerance in a co-culture of neurons and astrocytes in vitro after preliminary exposure to normobaric hypoxia and/or permissive hypercapnia in vivo. Preliminary hypoxic exposure increased the cell index throughout the 72-h period of observation, the effect of hypercapnia was observed on days 1 and 3 of the experiment, and the effect of hypercapnic hypoxia was noted only on day 1. Preliminary hypoxic exposure has a protective effect on nerve cells under conditions of chemical hypoxia. This suggests that hypercapnia and hypoxia activate proliferative activity of nerve cells, which can be viewed as a mechanism of their neuroprotective effectiveness.

[Positional deformity of the subclavian artery as a possible cause of subclavian steal syndrome]. / Pozitsionnaia deformatsiia podkliuchichnoi arterii kak vozmozhnaia prichina podkliuchichnogo steal-sindroma.

Using the method of duplex scanning, we examined a total of 123 patients presenting with a deformity of the subclavian artery (SCA). We assessed the Doppler spectrum of blood flow in the zone of the SCA deformity, as well as in V2 and V4 segments of the ipsilateral vertebral artery (VA) at rest and in breath holding on inspiration. Deformity of the SCA was observed on the right in 91% of cases, on the left in 5%, and on both sides in 4%. Haemodynamic disorders in the ipsilateral VA as a change of the shape of the Doppler spectrum according to the type of steal syndrome were noted in 10.8% of cases, with a more pronounced impairment of blood flow at the intracranial level - in 78.6% of cases. It was determined that a deformity of the SCA was characterised by a decrease in angulation (up to complete straightening) and a reduction of the peak systolic velocity on deep inspiration, thus reflecting its positional nature. Patients with initial impairment of the Doppler spectrum in the VA demonstrated normalization of the spectrum on an intake of breath. Hence, the index of the peak systolic velocity of blood flow in the zone of the SCA deformity in combination with assessment of the Doppler spectrum in the ipsilateral VA on inhalation may be used for determining the haemodynamic significance of a deformity of the SCA.

Stress of the Endoplasmic Reticulum of Neurons in Stroke Can Be Maximally Limited by Combined Exposure to Hypercapnia and Hypoxia.

We studied the expression of chaperone GRP-78 and transcription factor NF-kB during the development of ischemic tolerance of the brain after combined and isolated exposure to hypoxia and hypercapnia. Combined exposure to hypoxia and hypercapnia maximally increased the expression of chaperone GRP-78 and transcription factor NF-kB, while the formation of ischemia-induced tolerance under conditions of hypercapnic hypoxia can be associated with activation of adaptive stress mechanisms in the endoplasmic reticulum. Under these conditions, hypercapnia in combination with hypoxia is a priority factor for activation of GRP-78 and transcription factor NF-kB.

Inhibition of Apoptosis is a Potential Way to Improving Ischemic Brain Tolerance in Combined Exposure to Hypercapnia and Hypoxia.

We compared the intensity of apoptosis in the peri-infarction area of the brain after isolated and combined exposure to hypoxia and hypercapnia prior to focal ischemic stroke modeling. Hypoxia and hypercapnia reduced the number of TUNEL-positive cells in the peri-infarction area, and their combination was most effective in comparison with effects of isolated exposures. The maximum neuroprotective effect of combined exposure to hypoxia and hypercapnia in comparison with isolated exposures was determined by inhibition of apoptosis in the peri-infarction zone.

Proliferative and Synthetic Activity of Nerve Cells after Combined or Individual Exposure to Hypoxia and Hypercapnia.

We compared synthetic and proliferative activity of brain cells in rats exposed hypoxia, hypercapnia, or both prior to experimental focal stroke. The mean number of nucleolus organizer regions in penumbra neurons did not change after normobaric hypoxia, but increased after permissive hypercapnia or hypercapnic hypoxia. These data attest to activation of proliferative and synthetic functions in nerve cells, which plays an important role in the neuroprotective mechanisms under conditions of combined exposure to hypoxia and hypercapnia.

Deformity of subclavian artery as a cause of formation of vertebral subclavian steal syndrome.

Presented herein are 3 clinical case reports concerning formation of vertebral subclavian steal syndrome in deformities of subclavian arteries. By means of duplex scanning, angiography and multispiral computed tomography it was shown that deformities of subclavian arteries in the first segment (proximal to the origin of the vertebral artery) with septal stenosing are accompanied by a typical dopplerographic picture_pattern of steal syndrome.

[OPTIMAL HYPERCAPNIC HYPOXIA CONDITIONS FOR INCREASING RESISTANCE TO ACUTE HYPOXIA].

The study was focused on finding an optimal length of hypercapnia-hypoxia sessions of training resistance to acute hypoxia and looking for benefits from reoxygenation intervals and intermittent training over daytime. It turned out that 3 days of a 5-minute hypercapnia-hypoxia session per day improved resistance to acute hypoxia explicitly and that a 30-minute session increased resistance to the highest rate. Two training sessions per day are no better than one session. Hypercapnia-hypoxia training with reoxygenation intervals are the least effective in comparison to the other modes of training.

[Hypercapnia--alternative hypoxia signal incentives to increase HIF-1α and erythropoietin in the brain].

Investigated the role of hypercapnic component in the mechanism of activation of HIF-1α and increase the synthesis of erythropoietin in the combined and the isolated impact of hypoxia and hypercapnia. It was found that the content of proteins of interest significantly increases both in isolated hypoxia and hypercapnia, and at their combined effect. Moreover, the hypercapnic hypoxia causes maximum activation of the synthesis and accumulation of erythropoietin HIF-1α, and permissive hypercapnia enhances their content more than hypoxic exposure.

[Cerebral blood flow and damage markers during ischemia/reperfusion of brain against a background of modulation of the kinin system's activity].

Cerebral hemodynamics' status under condition of experimental ischemia and following reperfusion of brain against a background of pharmacological modulation of kinins' formation, the kinin system's inhibition and depression of kinins' disruption was investigated by the method of hydrogenous clearance. The brain damage intensity during hypoperfusion of reperfusion period was measured by analyzing its damage markers. It was determined that the activation of kinins' formation by tripsin has a detrimental effect during ischemia/reperfusion of brain, producing an early development of hypoperfusion in reperfusion period, aggravating a brain damage. The depression of kinins' disruption by ACE-inhibitors leads to superfluous decreasing of local cerebral blood flow during hypoperfusion of reperfusion period. The inhibition of kinins' formation by contrykal improves the flow of reperfusion period, preventing the appearance of hypoperfusion and decreasing the brain damage intensity in comparison with a control group. On the whole an activation of the kinin system during ischemia/reperfusion of brain plays mostly pathogenetic role making worse the flow of reperfusion period and aggravating a brain damage.

[The role of VEGF, HSP-70 and protein S-100B in the potentiation effect of the neuroprotective effect of hypercapnic hypoxia].

Studied the role of VEGF, HSP-70 and S-100B in potentiating hypercapnia neuroprotective effect of hypoxia. Demonstrated that neuroprotective effects when exposed hypercapnic hypoxia-mediated protein synthesis increased S-100B, mainly due to the action of carbon dioxide, and not oxygen deficiency. Neuroprotective effects of HSP-70 due to hypoxia, but the combined effect of hypoxia and hypercapnia gives a significant increase in the synthesis of HSP-70 in comparison with the isolated effect of hypoxia. Vascularization activated equally as hypoxia and hypercapnia, without adding significant effects in combination. This suggests dominant effect hypercapnia, hypoxia compared in neuroprotection mechanisms related to protein S-100B, but not the protein VEGF, hypercapnia and potentiate the neuroprotective efficacy of hypoxia-related protein HSP-70.

[The role of adenosine Al receptors and mitochondrial K+ATP channels in the mechanism of increasing the resistance to acute hypoxia in the combined effects of hypoxia and hypercapnia].

We studied the role of the role of mitoK+ATp channels and Al-adenosine receptor in the mechanism of increasing the resistance to acute hypoxia after hypoxic, hypercapnic and hypercapnic-hypoxic preconditioning. It is shown that mitochondrial ATP-sensitive potassium channels and Al-adenosine receptors, an important mechanism of preconditioning have a high value to increase the resistance to acute hypoxia/ischemia in the combined effect of hypoxia and hypercapnia. However, with regard to the adenosine receptor, this mechanism is realized without the participation hypercapnic component, which apparently starts neuroprotection without activation of the adenosine Al receptors.

Neuroprotective effects of individual or combined exposure to hypoxia and hypercapnia in the experiment.

We studied the effects of hypoxic, hypercapnic, and hypercapnic-hypoxic exposures on brain tolerance to ischemia. All respiratory training modes had a neuroprotective effect, but the most pronounced effect was observed after exposure to hypercapnic hypoxia. Experimental stroke in rats preliminary exposed to hypercapnic hypoxia was associated with minimal neurological deficit and motor coordination disturbances in comparison with training modes.

[Helical (spiral or swirling) blood flow in cardiovascular system].

In article covers theoretical preconditions for the hypothesis about helical (spiral or swirling) blood flow in cardiovascular system followed by its experimental corroboration. The role of the modern blood flow visualization methods--such as Color Doppler ultrasound and magnetic-resonance angiography--in registration and investigation of the regularities of the given phenomenon is described. The data describing the known parameters of helical blood flow--such as direction of the rotation and its quantitative parameters in large arteries--are given. The main hypotheses for flow screw mechanisms are considered from the point of view of cardiovascular system structural organization. Biological role of helical blood flow is discussed, in respect of which there are diametrically opposed points of view, which consider it as a physiological phenomenon on one side, and as a patogenetic factor of atherosclerosis development on the other.

[The response of cerebral blood flow and systemic arterial blood pressure to hypercapnia and hypocapnia in humans].

In 11 healthy volunteers 21 +/- 3.7 years old was monitored cerebral blood flow (CBF) by transcranial Doppler (TCD) of middle cerebral artery and mean hemodynamic arterial blood pressure (MAP) by continuous non-invasive measurement "beat-to-beat" at normocapnia, hypercapnia and hypocapnia. Hypercapnia was creating by rebreathing, hypocapnia was creating by spontaneous hyperventilation. The partial pressure of CO2 in alveolar air (PetCO2) was monitored by capnograph, embedded in the TCD-analyzer. During hypercapnia the velocity of CBF and PetCO2 were significantly increased already at 10 s, which was considerably earlier than the increase in the MAP (30 s). During hypocapnia velocity CBF and PetCO2 were significantly decreased at 10 s, and MAP was not changed. We have installed the threshold PetCO2 42 (41; 44) mm Hg, below which amplification CBF occurs at a constant MAP and reflects the true cerebrovascular reactivity to CO2.

[Comparative efficacy of hypoxia, hypercapnia and hypercapnic hypoxia increases body resistance to acute hypoxia in rats].

The relative efficiency of trainings with isolated hypoxia, hypercapnia and hypoxia in aggregate with hypercapnia in order to enhance the resistance of organism to the effect of an extreme hypoxia was studied. The combined effect of the hypoxia and hypercapnia was shown to influence more greatly in comparison with the effect of an isolated hypoxia. This effect was supported with an increase in the time of the loss position and the time of the animal's life under the condition of an extreme hypoxia. Also it is shown that the hypercapnia in a combination to a hypoxia makes dominating impact on formation of nonspecific resistance as the isolated hypercapnia enlarges indicators of nonspecific resistance, than the isolated hypoxia more effectively.

[Increased resistance to hypoxia under the effect of the mixture of herbs from the Altai].

We investigated the antihypoxic effect of herb mixture <> from the Altai in an experiment with rats. This mixture of herbs contains bioflavonoids. Also, it has antioxidant, anti-inflammatory, antispasmodic, angioprotective and antiplatelet properties. The animals received decoction of herbs into the stomach through a tube. Courses lasted 3, 7, 14 and 21 days. Resistance to acute hypobaric hypoxia evaluated by time of animal life in modeling rise to a height of 11,500 meters above sea level. In result, a significant antihypoxic effect was observed in rats treated with decoction of herbs for 21 days. Shorter courses of treatment were not effective.

[Ultrasonographic assessment of carotid stenoses: methods, possibilities and limitation].

The results of a multicenter study have shown that the degree of carotid stenosis makes it possible to forecast cerebral ischaemia and is a principle index for choosing between conservative and surgical treatment. Many centres perform carotid revascularization based only on the data of duplex scanning. Presented in the review are methods of ultrasonographic assessment of the stenosis degree, their comparative characteristics and factors influencing the accuracy of assessing the stenosis degree. Also considered herein are possibilities of standardization of carrying out studies and formations of conclusions.

[The mutation of genes of hemostasis system in patients with venous cerebral angiodystonia against the background of connective tissue dysplasia].

The examination was applied to sampling of 238 patients of younger age with neurologic symptomatology under connective tissue dysplasia and 46 healthy persons. The venous cerebral angiodystonia was diagnosed in 153 (64.3%) patients with connective tissue dysplasia. The results are confirmed by duplex analysis of cerebral and vertebral vessels. The mutations of genes of blood coagulation system (FV Leiden, FII, MTHFR, FVII and PAI-1) are established. They include combined (61.4%) and independent (23.5%) groups of mutation. Alongside with it, in 23 (19.6%) patients disorders of hemostasis are presented as von Willebrand factor deficiency and in 105 (89.7%) patients as decrease of aggregation function of thrombocytes and disorders of final coagulation stage of blood coagulation. The results of study indicate the equally frequent risk of thrombotic and hemorrhagic complications in patients with connective tissue dysplasia.

Hypercapnia Modulates the Activity of Adenosine A1 Receptors and mitoK+ATP-Channels in Rat Brain When Exposed to Intermittent Hypoxia.

The mechanisms and signaling pathways of the neuroprotective effects of hypercapnia and its combination with hypoxia are not studied sufficiently. The study aims to test the hypothesis of the potentiating effect of hypercapnia on the systems of adaptation to hypoxia, directly associated with A1-adenosine receptors and mitochondrial ATP-dependent K+ -channels (mitoK+ATP-channels). We evaluated the relative number of A1-adenosine receptors and mitoK+ATP-channels in astrocytes obtained from male Wistar rats exposed to various respiratory conditions (15 times of hypoxia and/or hypercapnia). In addition, the relative number of these molecules in astrocytes was evaluated on an in vitro model of chemical hypoxia, as well as in the cerebral cortex after photothrombotic damage. This study indicates an increase in the relative number of A1-adenosine receptors in astrocytes and in cells next to the stroke region of the cerebral cortex in rats exposed to hypoxia and hypercapnic hypoxia, but not hypercapnia alone. Hypercapnia and hypoxia increase the relative number of mitoK+ATP-channels in astrocytes and in cells of the peri-infarct region of the cerebral cortex in rats. In an in vitro study, hypercapnia mitigates the effects of acute chemical hypoxia observed in astrocytes for A1-adenosine receptors and mitoK+ATP-channels. Hypercapnia, unlike hypoxia, does not affect the relative number of A1 receptors to adenosine. At the same time, both hypercapnia and hypoxia increase the relative number of mitoK+ATP-channels, which can potentiate their protective effects with combined exposure.

[Formation of vertebral-subclavian steal syndrome in abnormal origin of the left vertebral artery from the aortic ark].

Presented herein is a clinical case report concerning the formation of vertebral-subclavian steal syndrome combined with occlusion of the left subclavian artery and an abnormal origin of the left vertebral artery from the aortic arch. Duplex scanning data and angiography findings showed that the collateral compensation of haemocirculation in the upper extremity took place through the subclavian-vertebral collateral net. Doppler ultrasonography signs of the latent steal syndrome were revealed in the intracranial segment of the left vertebral artery and were confirmed by the findings of the reactive hyperthermia test. Balloon angioplasty with stenting of the 1st portion of the left subclavian artery resulted in normalization of the Doppler spectrum in the intracranial segment of the left vertebral artery.