Experimental Hypoxia Research Articles

Honey Extracted Polyphenolics Reduce Experimental Hypoxia in Human Keratinocytes Culture.

Hypoxic assault affects fundamental cellular processes and generates oxidative stress on healthy cells/molecules. Honey extracted polyphenolics (HEP) as a natural antioxidant reduced hypoxic cytotoxicity in this study. Different honey samples were physicochemically characterized to identify preferred (jamun) honey [pH 3.55 ± 0.04, conductivity (μs/cm) = 6.66 ± 0.14, water content % (w/w) = 14.70 ± 0.35, total solid content % (w/w) = 85.30 ± 0.35, phenol content (mg GAE/100 g) = 403.55 ± 0.35, flavonoid content (mg QE/100 g) = 276.76 ± 4.10, radical scavenging activity (% 500 μL) = 147.75 ± 3.13, catalase activity (absorbance at 620 nm) = 0.226 ± 0.01]. HEP was tested in different doses on hypoxic and normoxic cells (HaCaT) using viability and antioxidant assays. Cardinal molecular expressions such as cadherin-catenin-cytoskeleton complex (namely, E-cadherin, β-catenin, and F-actin), hypoxia marker (Hif 1 α), proliferation marker (Ki67), and epithelial master regulator (p63) were studied by immuno-cytochemisty (ICC) and qRT-PCR. The 0.063 mg/mL HEP demonstrated better vitality and functionality of HaCaT cells as per viability assay (*, P < 0.01) even under hypoxia. ICC and qRT-PCR observations indicated restoration of cellular survival and homeostasis under 0.063 mg/mL HEP after hypoxic assault. Furthermore, major spectral changes for nucleic acid and membrane phospholipid reorganizations by Fourier transform infrared spectroscopy illustrated a positive impact of 0.063 mg/mL HEP on hypoxic cells considering proliferation and cellular integrity. It was concluded that a specific dose of jamun HEP reduces hypoxic cytotoxicity.

Morphological peculiarities of aorta and pulmonary artery in newborns after acute postnatal hypoxia in experiment.

Background. Intrauterine hypoxia of fetus and newborn asphyxia occupy one of the first places in the structure of perinatal morbidity and mortality, and reach 67.0% and 43.0%, respectively. The endured hypoxia decreases adaptive opportunities of the child's organism with negative effect on all organs and systems, including cardiovascular system affected in this pathological condition in 40-70 % cases. Objective. The aim of research is to make comparative analysis of the pathomorphological features of the pulmonary artery and aorta of newborn rats with acute postnatal hypoxia in experiment. Methods. Our experimental research on modeling acute postnatal hypoxia was performed on laboratory rats line WAG. Pregnant rats were not exposed to oxygen starvation, however, their descendants were exposed to alpine hypoxia corresponding to elevation of 7,500 meters for 20 minutes one time in the first 24 hours of life, and then were removed from the experiment. The resulting material was subjected to macroscopic, microscopic, morphometric methods of investigation. Results. Macroscopic examination of the pulmonary artery and aorta was carried out with a magnifier (×3, 8 diopters). Both vessels were elastic with smooth inner membrane. Microscopically, the wall of the pulmonary artery, as well as the aorta, consisted of three membranes – internal (tunica intima), medium (tunica media), and external (tunica adventitia). Indexes of the relative volume of tunica intima and media of the aorta decreased significantly relative to the pulmonary artery, and the volumes of tunica adventitia increased, most likely because of edema caused by increased vascular permeability due to hypoxia. The findings can be associated with activation of fibulin, fibrillin and emilin proteins what are responsible for these fibers formation. Violation of elastic and collagen fibers ratio in the aorta, towards the latter, decreases vessel elastic properties. The adventitial membrane of both vessels is edematous, with signs of sclerotic changes. It is formed by collagen and elastic fibers, full-blooded vasa vasorum, lymphatic vessels, without degenerative signs in nervi vasorum. Conclusion. Morphological signs of endothelial dysfunction were observed in the pulmonary artery and in the aorta of newborns with acute postnatal hypoxia. There is disturbance in the ratio of the elastic and collagen fibers in the aorta toward the second one under the acute postnatal hypoxia influence, what deteriorates the elastic vessel wall properties. On the contrary, elastic fibers predominate in the pulmonary artery. It can be related to activation of proteins what are responsible for these fibers formation. Thus, the carried out experiment demostrated significant pathomorphological changes in the pulmonary artery and aorta, what can lead to vascular pathology in future.

Combined preconditioning with tetra-(1-vinylimidazole) cobalt dichloride

The aim of this study was to investigate the vinylimidazole derivative as pharmacological preconditioning in experimental acute hypoxia and cerebral ischemia. All experiments were conducted with mice and rats. Acute hypoxia with hypercapnia was modeled by placing the mice in a glass with a glass lid shtanglazy 250 ml. Acute hypobaric hypoxia was performed putting animals under a glass cope, where from the Kamovsky pump pumped up the air which is equal to the altitude of 5000 meters (moderate hypoxia) and 11 000 meters (severe hypoxia). Cerebral ischemia in rats was modeled by one-stage bilateral common carotid artery occlusion. Separate pharmacological and hypoxic preconditioning and combined preconditioning by alternately use of pharmacological and hypoxic factors were investigated. It was revealed that combined preconditioning (tetra-(1-vinylimidazole) cobalt dichloride 30 mg/kg + moderate hypobaric hypoxia) enhance the resistance of the animal organism to acute hypoxia in the early period (in 1 hr) and delayed period (in 48 hr) more effective than the separate preconditioning by moderate hypoxia or with the help of tetra-(1-vinylimidazole) cobalt dichloride. The combined preconditioning increase the survival of rats in the early periods and in the delayed periods of cerebral ischemia performance, but doesn’t reduce the severity of neurological deficit in the surviving animals registered with the Stroke Index McGraw scale.

Brain neurochemical and hemodynamic findings in the NY1DD mouse model of mild sickle cell disease.

To characterize the cerebral profile associated with sickle cell disease (SCD), we used in vivo proton MRI and MRS to quantify hemodynamics and neurochemicals in the thalamus of NY1DD mice, a mild model of SCD, and compared them with wild-type (WT) control mice. Compared with WT mice, NY1DD mice at steady state had elevated cerebral blood flow (CBF) and concentrations of N-acetylaspartate (NAA), glutamate (Glu), alanine, total creatine and N-acetylaspartylglutamate. Concentrations of glutathione (GSH) at steady state showed a negative correlation with BOLD signal change in response to 100% oxygen, a marker for oxidative stress, and mean diffusivity assessed using diffusion-tensor imaging, a marker for edematous inflammation. In NY1DD mice, elevated basal CBF was correlated negatively with [NAA], but positively with concentration of glutamine ([Gln]). Immediately after experimental hypoxia (at reoxygenation after 18hours of 8% O2 ), concentrations of NAA, Glu, GSH, Gln and taurine (Tau) increased only in NY1DD mice. [NAA], [Glu], [GSH] and [Tau] all returned to baseline levels two weeks after the hypoxic episode. The altered neurochemical profile in the NY1DD mouse model of SCD at steady state and following experimental hypoxia/reoxygenation suggests a state of chronic oxidative stress leading to compensatory cerebral metabolic adjustments.

Effect of acadesine on breast cancer cells under hypoxia

The riboside derivative acadesine (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside) is currently being tested in clinical trials as a promising anti-tumor drug. Intracellular target of acadesine is adenosine monophosphate-activated protein kinase (АМРК), an important regulatory molecule of energy metabolism. It is expected that acadesine would be active in tumors under hypoxia conditions. In normoxia (cells incubated in 21 % oxygen), acadesine inhibited proliferation and induced cell death of breast adenocarcinoma, including the triple negative breast cancer line. When oxygen partial pressure was decreased to 1 % (experimental hypoxia), acadesine inhibited activation of reporter construct responsive to HIF-1α (hypoxia inducible factor 1 alpha) transcription factor. This effect was observed for acadesine in concentrations close to cytotoxic. Acadesine retained cytotoxicity under hypoxia and decreased the survival of the MDA-MB-231 cell line when used in combination with cisplatin. These results considerably widen acadesine’s field of application and allow to assume its efficacy in chemotherapy combination regimens for breast cancer, including the tumors with low oxygenation.

Protective effect of grapes polyphenol concentrate “Fenokor” in terms of hypoxic myocardial injury

Polyphenols of grapes and their beneficial effects on human health have been known for a long time and still attract more and more research interest. The aim of the research was to reveal cardioprotective properties of polyphenols contained in grape concentrate “Fenokor” in terms of experimental histotoxic hypoxia. Materials and methods. The study was conducted on 21 adult male Wistar rats divided into 3 groups, 2 of which were administered CoCl2 aqueous solution in a dose of 60 mg/kg for 7 days intragastrically. The control group consisted of 5 intact animals. The rats of the second group (n = 8) after the introduction of the cobalt did not receive any treatment, the animals of the third group (n = 8) after the administration of cobalt chloride intragastrically, were given Fenokor aqueous solution at a dose of 2,5 ml/kg along with 0,05 ml of water orally. Morphological study was performed using light and electron microscopy. During the experiment the following biochemical parameters such as contents of malondialdehyde, oxidative modification of proteins were estimated. The results. The result of the influence of cobalt on the heart of animals in experiments is the development of severe cardiomyopathy that requires cardio-protection. Histological structure of myocardium observed in the second group of male rats after cobalt intoxication on the background of grape polyphenol concentrate generally reflected a tendency to minimize the damage extent which was manifested in the form of normalization of cell structures and muscle fibers. Application of Fenokor has demonstrated its antioxidant and cytoprotective properties, which contributed to myocardial structure preservation in rats exposed to histotoxic hypoxia.

Inflammatory hypoxia induces syndecan-2 expression through IL-1β-mediated FOXO3a activation in colonic epithelia.

Chronic inflammation is known to be a key causative factor in tumor progression, but we do not yet fully understand the molecular mechanism through which inflammation leads to cancer. Here, we report that the dextran sulfate sodium (DSS)-induced mouse model of chronic colitis is associated with increases in the serum level of IL-1β and the colonic epithelial expression of the cell-surface heparan sulfate proteoglycan, syndecan-2. We further show that IL-1β stimulated the transcription of syndecan-2 via NF-κB-dependent FOXO3a activation in CCD841CoN normal colonic epithelial cells and early-stage HT29 colon cancer cells. Inflammatory hypoxia was observed in the colonic epithelia of mice with chronic colitis, suggesting that hypoxic stress is involved in the regulation of syndecan-2 expression. Consistently, experimental inflammatory hypoxia induced hypoxia inducible factor-1α-dependent FOXO3a expression and the p38 MAPK-mediated nuclear localization of FOXO3a. FOXO3a directly mediated syndecan-2 expression in both cell lines and the colonic epithelia of mice with DSS-induced colitis. Moreover, syndecan-2 expression was detected in azoxymethane/DSS-induced colon tumors. Together, these data demonstrate that inflammatory hypoxia up-regulates syndecan-2 via the IL-1β-NF-κB-FOXO3a pathway. These findings provide new mechanistic insights into inflammatory hypoxia-mediated syndecan-2 expression to connect chronic inflammation and the development of colon cancer.-Choi, S., Chung, H., Hong, H., Kim, S. Y., Kim, S.-E., Seoh, J.-Y., Moon, C. M., Yang, E. G., Oh, E.-S. Inflammatory hypoxia induces syndecan-2 expression through IL-1β-mediated FOXO3a activation in colonic epithelia.

Features of an Expression of Smooth Muscle Actin by Muscle Cells of Arterioles and Venules of Ureter and Urinary Bladder of Newborns in Modeling Chronic Intrauterine Hypoxia

Introduction/ Background Chronic intrauterine hypoxia, accompanied numerous complications of pregnancy, is one of the damaging factor of the organism of fetus and newborn. Aims The purpose – to reveal the features of expression of smooth muscle actin by muscle cells of arterioles and venules of ureter and urinary bladder of newborns under the influence of experimental chronic intrauterine hypoxia. Methods An experiment was conducted on modeling high mountain hypoxia in rats of WAG line. Two groups were formed: I – newborns (n=11) born from 3 rats that were not subjected to high mountain hypoxia; II – newborns (n=10) born from 4 rats that throughout pregnancy were exposed to a daily high mountain hypoxia. The material of the study was the tissue of ureter and urinary bladder. It was used peroxidase reaction with the monoclonal antibodies to smooth muscle actin (DAKO, Denmark). The slides were studied in microscope «Olympus ВХ- 41». An experimental study was carried out in strict compliance with the requirements of the European convention (Strasbourg, 1986) on the housing, feeding and care of experimental animals, and their removal from the experiment. Mean values of indicators in groups were compared using a nonparametric U-criteria Mann-Whitney. Results In group I and II was observed expression of smooth muscle actin by muscle cells, forming muscle fibers and including in the tunica media of arterioles and venules of ureter and urinary bladder, in a clear cytoplasmic staining in brown. In group I the mean values of indicators of thickness of muscle fibers in arterioles and venules of ureter were respectively (2,19±0,229)×10-6m and (1,38±0,189)×10-6m; in urinary bladder – (2,92±0,207)×10-6m and (2,11±0,160)×10-6m. In group II the mean values of indicators of thickness of muscle fibers in arterioles and venules of ureter were respectively (1,67±0,270)×10-6m and (0,88±0,107)×10-6m; in urinary bladder – (2,20±0,198)×10-6m and (1,49±0,239)×10-6m. Analyzing and comparing the obtained values, it was observed that in group I and II was determined significant predominance (р 0,05) were absent. In group II in ureter and urinary bladder was a significant (р<0,05) decreasing of the mean values of indicators of thickness of muscle fibers in arterioles and venules in comparison with group I. Conclusion: Chronic intrauterine hypoxia leads to a thinning of the thickness of the muscle fibers in arterioles and venules of ureter and urinary bladder in newborns.

The acute and delayed effects of perinatal hypoxic brain damage in children and in model experiments with rodents

Perinatal hypoxia is an important factor that has a negative influence on the development of the central nervous system. Children who experience perinatal hypoxia are characterized by disturbances of locomotor functions, decreased learning abilities, attention disorder, hyperactivity, increased anxiety, and other cognitive impairments. The consequences of perinatal hypoxia are actively studied in experiments with animals. It has been shown that hypoxia triggers a cascade of biochemical and molecular processes, such as energy insufficiency, depolarization of membranes, an increase in the release of mediators and suppression of their reuptake, an increase in the intracellular calcium level, and production of free radicals, which damage neurons and induce neurodegeneration and cell death. Simultaneously, compensatory-adaptive mechanisms that increase the resistance of the body to an oxygen deficit also begin to function in hypoxia. Further studies on the consequences of neonatal hypoxia in experiments with animals are necessary for the elucidation of the mechanisms of the acute and delayed effects of hypoxia, as well as for development of effective means for the correction of the negative consequences of perinatal hypoxia in clinics.

Особливості розвитку адаптації організму за умов експериментальної гострої гіпоксії залежно від вихідного рівня вегетативного забезпечення

Особливості розвитку адаптації організму за умов експериментальної гострої гіпоксії залежно від вихідного рівня вегетативного забезпечення

Translational Challenge Models in Support of Efficacy Studies: Effect of Cerebral Hypoxia on Cognitive Performances in Rodents

Empirical evidence currently supports the idea that neurovascular dysfunction is involved in the neurodegenerative process of Alzheimer's disease (AD). In fact, epidemiological studies report that i) vascular risk factors are directly associated with an increased incidence of AD and ii) vascular lesions are frequently co-existent with AD. The neurovascular unit is a key control system for oxygen and nutrients exchange between neurons and microvessels so the integrity of this system is essential for neuronal activity and cell survival. This suggests that hypoxia arising from various vascular injuries may participate in the pathogenesis of AD and aggravate cognitive deficit. Moreover, hypoxia appears to have a direct effect on cognitive functions, in particular memory, by inducing a transient or definitive dysfunction of synaptic transmission. The interplay of hypoxic phenomenon and the development of AD-related pathologies support the use of hypoxia as a challenge model to assess symptomatic (i.e. cognitive enhancers) AD-treatment. Such challenge should be characterized and validated with current symptomatic drugs based on different mechanisms of action before being offered as alternative models for testing new drugs. To date, symptomatic treatments of AD including anticholinesterasic- (donepezil, rivastigmine and galantamine) and antiglutamatergic- (memantine) drugs target various neurotransmission impairments occurring at different stages of the disease. The first aim of the present review is to provide an overview of the methods used to achieve experimental hypoxia in rodents and to characterize the cognitive alterations induced by each method. The second objective is to summarize the main results from studies that have tested the effect of acetylcholinesterase inhibitors on hypoxiainduced cognitive impairment. Overall, the literature research yielded only a small number of studies investigating the effect of hypoxia on cognition in rodents and the different models described sometime differ substantially in terms of timing, severity and nature of cognitive impairment. Chronic exposure to intermittent normobaric or continuous hypobaric hypoxia induced persistent spatial reference and working memory alterations. In contrast, acute hypoxia exposure was shown to induce more transient associative and spatial memory impairments. Treatment with acetylcholinesterase inhibitors was shown to improve hypoxia-induced memory impairment in various hypoxia protocols.

Engineering a solution to explore the cardiorespiratory limits to exercise performance: take a load off!

Engineering a solution to explore the cardiorespiratory limits to exercise performance: take a load off!

Histopathological alterations in triangle sail mussel (Hyriopsis cumingii) exposed to toxic cyanobacteria (Microcystis aeruginosa) under hypoxia

Bloom-forming microalgae and hypoxia are considered as the two main co-occurring stressors associated with eutrophication. How these two stressors might alter the sail mussel exposed to toxic cyanobacteria and hypoxia has not been well evaluated histophysiologically. Therefore, the present study was designed to evaluate the combined effects of the harmful cyanobacteria (Microcystis aeruginosa) and hypoxia on the histopathological alterations in the gill, digestive gland, and stomach of an ecologically and economically important mussel species inhabiting lakes and reservoirs, the triangle sail mussel (Hyriopsis cumingii). To evaluate the histophysiological changes due to the stressors, a 2×2 factorial design with four treatments was adopted: two dissolved oxygen levels (hypoxia: 1mgO2l−1; normoxia: 6mgO2l−1) and two treatments, one with 0% and another with 100% (1.8×107cellml−1 ca. 50mgl−1) cell biomass of toxic M. aeroginosa. The non-toxic green alga (Chlorella vulgaris) was supplemented to maintain the same algal biomass in the four treatments. Samples from the treatments were collected on days 0, 3, 5, 7, 14, and 21. The microcystin content in sail mussels exposed to M. aeruginosa increased over the entire experimental span, under both normoxia and hypoxia, but was significantly lower in mussels under hypoxic conditions. Pathological alterations were observed in the gills, digestive diverticula and stomach of mussels under hypoxia, when fed 100% M. aeruginosa diet, and when intoxicated with M. aeruginosa under hypoxia. Hyperplasia, exfoliation of latero-frontal cilia, filament fusion, and epithelial desquamation of filaments in the gills were observed following 7days of exposure to M. aeruginosa and hypoxia. After 7days of exposure, the damage in the gills, digestive gland, and stomach increased. Hypoxia induced more severe effects in the gill structures than the harmful alga, whereas the digestive gland was more affected by exposure to M. aeruginosa. The stomach, however, was equally affected by both stressors. Results of this preliminary study highlight the need for further in depth studies on the combined effect of toxic cyanobacteria and hypoxia on the triangle sail mussel, and the potential implications for the freshwater pearl production in China. Statement of relevanceHyriopsis cumingii has been considered as an aquaculture species for pearl production in China. In recent years, the mussels have been often suffered from hypoxia and toxic algae, but the effects of Microcystis aeruginosa associated with hypoxia on the morphological changes of selected organs such as gill, digestive gland and stomach are unclear. This study just clarified that the selected tissues of H. cumingii were more severely affected by the both stressors, which may clarify how the toxic algae and hypoxia cause some diseases in the mussel H. cumingii.

Antihypoxic and Neuroprotective Effects of Glial Cell-Derived Neurotrophic Factor (GDNF) in Cultures of Dissociated Hippocampal Cells under Conditions of Experimental Hypoxia

We analyzed the effect of glial cell derived neurotrophic factor (GDNF) on changes in functional bioelectric and calcium activity in dissociated hippocampal cell cultures under conditions of modeled acute normobaric hypoxia in vitro. GDNF (1 ng/ml) partially neutralized the negative effects of hypoxia on cell survival and parameters of functional network activity. GDNF exhibited a pronounced anti-hypoxic effect.

Sympathetic Vasoconstrictor Responsiveness of the Leg Vasculature During Experimental Endotoxemia and Hypoxia in Humans.

Sympathetic vasoconstriction regulates peripheral circulation and controls blood pressure, but sepsis is associated with hypotension. We evaluated whether apparent loss of sympathetic vasoconstrictor responsiveness relates to distended smooth muscles or to endotoxemia and/or hypoxia. Prospective descriptive study. Hospital research laboratory. Ten healthy young men (age [mean ± SD], 31 ± 8 yr; body weight, 83 ± 10 kg) participated in the study. Leg blood flow and mean arterial pressure were determined, whereas leg vascular conductance was calculated during 1) adenosine infusion (vasodilator control), 2) hypoxia (FIO2 = 10%), 3) endotoxemia, and 4) endotoxemia + hypoxia. Leg sympathetic vasoconstrictor responsiveness (reduction in leg vascular conductance) was evaluated by femoral artery tyramine infusion. Endotoxemia increased body temperature from 36.9 ± 0.4°C to 38.6 ± 0.5°C (p < 0.01) and plasma tumor necrosis factor-α from 6 pg/mL (3-8 pg/mL) to 391 pg/mL (128-2258 pg/mL) (p < 0.01; median [range]). Mean arterial pressure decreased similarly during endotoxemia (-11% ± 16%) and endotoxemia + hypoxia (-10% ± 15%; both p < 0.05). Leg blood flow and leg vascular conductance were not affected by endotoxemia, whereas both were elevated by adenosine infusion (leg blood flow, +94% ± 61%; leg vascular conductance, +97% ± 57%), hypoxia (leg blood flow: +93% ± 58%; leg vascular conductance, +100% ± 115%), and endotoxemia + hypoxia (leg blood flow, +67% ± 120%; leg vascular conductance, +65% ± 57%; p < 0.05). Endotoxemia lessened the tyramine-induced reduction in leg vascular conductance (-28% ± 13%) compared with the reduction during adenosine infusion (-47% ± 5%; p < 0.05). Also, endotoxemia + hypoxia (-17% ± 21%) attenuated the tyramine-induced reduction in leg vascular conductance compared with both adenosine infusion and hypoxia (-45% ± 13%; p < 0.05). Both endotoxemia and combined hypoxia and endotoxemia blunted sympathetic vasoconstrictor responsiveness. Furthermore, tyramine normalized the doubled leg vascular conductance during administration of adenosine, suggesting that distension of vascular smooth muscles does not explain blunted sympathetic vasoconstrictor responsiveness during endotoxemia.

Delayed Onset and Reduced Cognitive Deficits through Pre-Conditioning with 3-Nitropropionic Acid is Dependent on Sex and CAG Repeat Length in the R6/2 Mouse Model of Huntington's Disease.

Impairments in energy metabolism are implicated in Huntington's disease (HD) pathogenesis. Reduced levels of the mitochondrial enzyme succinate dehydrogenase (SDH), the main element of complex II, are observed post mortem in the brains of HD patients, and energy metabolism defects have been identified in both presymptomatic and symptomatic HD patients. Chemical preconditioning with 3-nitropropionic acid (3-NP), an irreversible inhibitor of SDH, has been shown to increase tolerance against experimental hypoxia in both heart and brain. Here we studied the effect of chronic preconditioning in the R6/2 mouse model of HD using mice carrying CAG repeat lengths of either 250 or 400 repeats. Both are transgenic fragment models, with 250CAG mice having a more rapid disease progression than 400CAG mice. Low doses of 3-NP (24 mg/kg) were administered via the drinking water and the effect on phenotype progression and cognition function assessed. After 3-NP treatment there were significant improvements in all aspects of the behavioural phenotype, apart from body weight, with timing and magnitude of improvements dependent on both CAG repeat length and sex. Specifically, a delay in the deterioration of general health (as shown by delayed onset of glycosuria and increased survival) was seen in both male and female 400CAG mice and in female 250CAG mice and was consistent with improved appearance of 3-NP treated R6/2 mice. Male 250CAG mice showed improvements but these were short term, and 3-NP treatment eventually had deleterious effects on their survival rate. When cognitive performance of 250CAG mice was assessed using a two-choice discrimination touchscreen task, we found that female mice showed significant improvements. Together, our results support the idea that energy metabolism contributes to the pathogenesis of HD, and suggest that improving energy deficits might be a therapeutically useful target.

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

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.

Вплив блокування м1-холінорецепторів асоціативної кори дорослих щурів на автономну регуляцію серцевого ритму при гіпоксичному впливі

&lt;p&gt;Резюме. Моделювання атмосферної гіпоксії в експерименті на щурах дозволяє більш детально дослідити участь речовин медіаторної дії у формуванні адаптації регуляторних систем мозку до гіпоксичного впливу. Метою експерименту було виявити функціональні наслідки блокування м&lt;sub&gt;1&lt;/sub&gt;-холінорецепторів в асоціативній корі дорослих щурів у гіпоксичному середовищі за умов зниженого атмосферного тиску. За умов експериментальної гіпоксії спостерігали функціональну перебудову включення холінергічних структур до механізмів автономного контролю серцевого ритму. Інкубація дорослих щурів у гіпоксичному середовищі за умов зниженого атмосферного тиску, аналогічному природним умовам ІІІ типу погоди, призводить до активації холінергічної регуляції серцевого ритму.&lt;/p&gt;&lt;p&gt; &lt;/p&gt;&lt;p&gt;Ключові слова: блокування м&lt;sub&gt;1&lt;/sub&gt;-холінорецепторів, асоціативна кора, знижений атмосферний тиск.&lt;/p&gt;

Migraine induced by hypoxia: an MRI spectroscopy and angiography study

Migraine with aura is prevalent in high-altitude populations suggesting an association between migraine aura and hypoxia. We investigated whether experimental hypoxia triggers migraine and aura attacks in patients suffering from migraine with aura. We also investigated the metabolic and vascular response to hypoxia. In a randomized double-blind crossover study design, 15 migraine with aura patients were exposed to 180 min of normobaric hypoxia (capillary oxygen saturation 70-75%) or sham on two separate days and 14 healthy controls were exposed to hypoxia. Glutamate and lactate concentrations in the visual cortex were measured by proton magnetic resonance spectroscopy. The circumference of cranial arteries was measured by 3 T high-resolution magnetic resonance angiography. Hypoxia induced migraine-like attacks in eight patients compared to one patient after sham (P = 0.039), aura in three and possible aura in 4 of 15 patients. Hypoxia did not change glutamate concentration in the visual cortex compared to sham, but increased lactate concentration (P = 0.028) and circumference of the cranial arteries (P < 0.05). We found no difference in the metabolic or vascular responses to hypoxia between migraine patients and controls. In conclusion, hypoxia induced migraine-like attacks with and without aura and dilated the cranial arteries in patients with migraine with aura. Hypoxia-induced attacks were not associated with altered concentration of glutamate or other metabolites. The present study suggests that hypoxia may provoke migraine headache and aura symptoms in some patients. The mechanisms behind the migraine-inducing effect of hypoxia should be further investigated.

The Effect of the Antioxidant Drug U-74389G on Magnesium Levels During Hypoxia–Reoxygenation Injury in Rats

The aim of this experimental study was to examine the effect of the antioxidant drug U-74389G in a rat model of hypoxia-reoxygenation using the previously established protocol. Effects of treatments were evaluated by magnesium (Mg2+) levels in blood. Non-randomized controlled study was performed. Mg2+ levels were determined in 60 min (groups A and C) and 120 min (groups B and D) after starting the reoxygenation. Groups A and B received no drugs, whereas rats from groups C and D were administered with U-74389G. 40 rats 16-18 weeks old of a mean weight of 2312 g were employed in the study. It is demonstrated that U-74389G administration did not alter the Mg2+ levels (decrease in Mg2+ concentration was 0.28±2.75%; p=0.917). Reoxygenation non-significantly increased the Mg2+ levels by 4.27±2.66% (p=0.107). Together, the U-74389G administration and reoxygenation non-significantly increased the Mg2+ levels by 0.36±1.64% (p=0.823). U-74389G administration, alone or in concert with reoxygenation did not significantly affect Mg2+ level in blood after experimental hypoxia in rats.