HEMOSTASIOLOGICAL PROFILE IN RATS UNDER SINGLE EXPOSURE TO SUBMAXIMAL AND MAXIMUM HYPERCAPNIC HYPOXIA

Author(s):  
S.V. Moskalenko ◽  
I.I. Shakhmatov ◽  
V.I. Kiselev ◽  
V.M. Vdovin ◽  
A.A. Blazhko

Hypoxia is the main link in the taxis pathogenesis to most extreme factors. It occurs in many pathological processes. The aim of the work was to study the hemostatic system in rats under a single exposure to submaximal and maximum hypercapnic hypoxia. Materials and Methods. The experiment enrolled 40 Wistar male rats. Single 20-minute hypercapnic hypoxia (HH) was modeled by placing the animals into a chamber with a gas mixture: submaximal HH: O2 – 9 %; CO2 –7 %; maximum HH: O2 – 5 %; CO2 – 5 %. Results. Single submaximal HH was accompanied by a decrease in the platelet number under a constant level of their aggregation activity. Hypercoagulable shift was observed along the internal pathway and at the final stage of coagulation against the decrease in fibrinogen concentration. AT III level decreased, however, there were no changes in blood APR. Single maximum HH led to more pronounced coagulable shifts. Platelet hemostasis responded by a decrease in the platelet number with a simultaneous increase in their aggregation activity. As for coagulation hemostasis, hypercoagulation was recorded at all stages of coagulation. At the same time, fibrinogen concentration in blood plasma decreased, and the level of soluble fibrin-monomer complexes (SFMCs) significantly increased. The authors reported an increase in plasma fibrinolytic activity. Conclusion. Thus, upon a single exposure to submaximal HH, hypercoagulation was not yet accompanied by thrombinemia markers. At the same time, the danger of thrombotic state development remained, since the hypercoagulable shift was recorded against a decrease in blood plasma anticoagulant activity. A further increase in HH intensity was accompanied by deteriorating hemostatic functions of experimental animals, which could be described as a state of thrombotic readiness. A decrease in the anticoagulant level in response to maximum HH exacerbated thrombosis risks. Keywords: hemostasis, hypercapnic hypoxia. Гипоксия выступает в качестве основного звена патогенеза ответной реакции организма на воздействие большинства экстремальных факторов и встречается во многих патологических процессах. Цель работы – изучить состояние системы гемостаза у крыс, подвергшихся однократному воздействию гиперкапнической гипоксии субмаксимальной и максимальной интенсивности. Материалы и методы. В эксперименте использовались крысы-самцы (40 особей) линии «Вистар». Однократная 20-минутная гиперкапническая гипоксия (ГКГ) моделировалась путем помещения животных в камеру, в которую подавалась смесь газов: ГКГ субмаксимальной интенсивности – 9 % О2, 7 % СО2; максимальной – 5 % О2, 5 % СО2. Результаты. Однократная ГКГ субмаксимальной интенсивности сопровождалась снижением количества тромбоцитов при неизменном уровне их агрегационной активности. Гиперкоагуляционный сдвиг отмечался по внутреннему пути и на конечном этапе свертывания на фоне снижения концентрации фибриногена. Уровень АТ III снижался, однако изменений со стороны АРП крови зафиксировано не было. Однократная ГКГ максимальной интенсивности приводила к более выраженным коагулологическим сдвигам. Тромбоцитарный гемостаз отреагировал снижением количества тромбоцитов при одновременном повышении их агрегационной активности. Со стороны коагуляционного гемостаза регистрировалась гиперкоагуляция на всех этапах свертывания. При этом концентрация фибриногена в плазме крови снижалась, уровень РФМК значительно повышался. Было зарегистрировано повышение фибринолитической активности плазмы крови. Выводы. Таким образом, по завершении однократного воздействия ГКГ субмаксимальной интенсивности гиперкоагуляция еще не сопровождалась появлением маркеров тромбинемии. При этом опасность развития тромботического состояния сохранялась, поскольку гиперкоагуляционный сдвиг регистрировался на фоне снижения антикоагулятной активности плазмы крови. Дальнейшее повышение интенсивности воздействия ГКГ сопровождалось ухудшением гемостатического статуса экспериментальных животных, что может быть охарактеризовано как состояние тромботической готовности. Снижение уровня антикоагулянта в ответ на ГКГ максимальной интенсивности увеличивало риск развития тромбообразования. Ключевые слова: гемостаз, гиперкапническая гипоксия.

2021 ◽  
Vol 22 (1) ◽  
pp. 52-59
Author(s):  
O.A. Vrzhesinskaya ◽  
◽  
V.M. Kodentsova ◽  
N.A. Beketova ◽  
O.V. Kosheleva ◽  
...  

The diet of the majority of the population of Russia is characterized by an insufficient content of a number of micronutrients, including macro- and micronutrients. The aim of the study is to characterize in a rat model experiment the effect of combined nutritional deficiency of calcium, magnesium and iodine on the availability of other mineral substances, vitamin metabolism and biochemical parameters blood plasma. The lack of minerals in growing Wistar male rats with an initial body weight (51.4 ± 0.5) g was created for 23 days by halving of a calcium, magnesium and iodine in the salt mixture. Alimentary deficiency of calcium, magnesium and iodine in growing rats significantly and multidirectionally affected the metabolism of other minerals and vitamins, as well as a number of diagnostically significant indicators of blood and urine. In rats of the experimental group, the liver concentration of α-tocopherol, vitamin B1 and retinol palmitate decreased, the concentration of iron and zinc increased, the copper content in the whole brain decreased significantly. The molar ratio of γ- and α-tocopherols in blood plasma was increased, the concentration of the circulating form of vitamin D decreased. The ratio of AlAT / AsAT (de Ritis coefficient) markedly decreased due to increased activity of AlAT. Phosphate reabsorption decreased slightly. Increased urinary excretion of riboflavin was accompanied by a decrease in its concentration in blood plasma. The conclusion that insufficient intake of calcium, magnesium and iodine may disturb vitamin-mineral status of organism has been made.


2015 ◽  
Vol 6 (1) ◽  
pp. 17-22
Author(s):  
A. I. Shevtsova ◽  
G. A. Ushakova

There is no standard as to treatment of anthracycline chemotherapy complications. The reduction of cytotoxic drugs toxicity without weakening of their antitumor action remains relevant. The extracellular matrix which key component is fibronectin is present in all tissues and it continuously undergoes controlled remodeling. So, the purpose of our work was to study the level of fibronectin in the experimental model of doxorubicin-induced cardiomyopathy and effects of this cytostatic and its co-administration with antioxidants of different nature.The level of fibronectin was measured by ELISA using monospecific antibodies against fibronectin (Sigma, USA), secondary anti-IgG labeled with horseradish peroxidase (Sigma, USA) and fibronectin standard (Sigma, USA). The study was conducted on Wistar male rats with weight of 210 ± 50 g which were divided into 4 groups by 8 animals in each group: 1 – control, rats receiving saline i/p; 2 – doxorubicin 1 mg/kg i/p once a week during 4 weeks; 3 – doxorubicin by the same scheme plus 1% 2-oxoglutarate in drinking water during 4 weeks;4 – doxorubicin by the same scheme and korvitin injection 30 min before doxorubicin application once a week during 4 weeks. Obtained data indicate the effect of doxorubicin to decrease in index mass heart in 38% of animals compared to control animals; decrease in total protein concentration by 8% (Р < 0,05) and increase of the level of fibronectin by 67% (P < 0,001) in blood plasma of rats and decrease in the level of fibronectin in the heart extract by 19% (Р < 0,05) under development of doxorubicin-induced cardiotoxicity. Increased fibronectin concentration in blood plasma had strong correlation with decreased total protein concentration in blood (r=0,80) and heart extract (r=0,59) in rats with doxorubicin-induced cardiomiophaty indicating the sensitive reaction of fibronectin to development of metabolic disorders under doxorubicin influence. 


2017 ◽  
pp. 67-71
Author(s):  
V. M. Sheybak ◽  
A. Y. Pavliukovets ◽  
V. Yu. Smirnov

Objective: to analyze the pool of free amino acids and their nitrogen-containing metabolites of blood plasma of animals being administered lead acetate for 21 or 28 days. Material and methods. The experiments were carried out on white male rats with the initial weight of 140-160 g. During the experiment the animals received a total amount of 0.67 g of lead acetate (21 days), the second group - 1.12 g (28 days). The determination of free amino acids in blood plasma was performed by the method of reversed-phase HPLC. Results. As a result of the research it has been found out that the most significant contribution to the formation of the amino acid imbalance in blood plasma as a result of the long-term intake of lead acetate according to the value of the Fisher test is caused by changes in the concentrations of α-aminobutyric acid, isoleucine, aspartate, arginine, glycine, serine, histidine, and methionine. Conclusion. The long-term intake of lead acetate with drinking water leads to a statistically significant increase of general content of free amino acids and their nitrogen-containing metabolites, as well as to a decrease of the concentration the essential amino acid threonine in blood plasma.


2019 ◽  
Vol 15 (1-2) ◽  
pp. 20-24
Author(s):  
N.G. Pobigun

Relevance. The chronic stress influences on increasing of frequency of thyroid pathology together with other factors (decreased iodine intake in food, harmful factors of external environment, high technogenic loading, depravation of general ecological state, violation of structure of nutrition). The changes of hypothalamus-hypophysis-thyroid gland axis at stress is not enough agreed because of influence stressful factors with different character and duration. Objective is study of influence of chronic emotional painful stress (CS) on the changes of morphofunctional state of thyroid gland (TG) on the background of experimental hypothyroidism (EH). Materials and methods. Experiments were performed on 48 white laboratory sex matured male rats. Animals were divided on four groups: the fist – intact animals; the second – animals with EH; the third – animals under influence of CS; the fourth – animals with EH under action of CS. The EH was modeled by everyday addition of mercazolilum (dose 10mg/kg) to drinking water during 15 days. The CS was modeled by 1 hour per day during 30 days. The functional activity of TG was estimated by the concentration of thyroid stimulating hormone (TSH), triiodothyronine (T3), thyroxin (T4) in blood plasma and calculation of thyroid index (TI). The morphological state of TG was studied by light and electron microscopy. The statistical analysis of results was processed using Student’s test with Bonferroni-Holm correction in program Statistica 6.0. The differences were statistical significant at р<0,05.             Results. The long-term influence of stress factors caused significant decreasing of level of thyroid hormones in blood plasma in comparison to intact animals. The data of light and electron microscopy of TG of rats under influence of CS confirm biochemical changes and detect signs of decreasing of secretory function. On the background of action of mercazolilum the long-term stress caused to more substantial changes of functional state of TG (significant increasing of level of TSH, decreasing of content of T4 and TI) in comparison to data of animals with EH. The structural features of TG of animals with EH under influence of CS indicate on suppression of function. Conclusions. Decreasing of synthesis of hormones by TG in rats at conditions of CS was detected. The long-term action of stress on background of hypothyroidism causes to more substantial depravation of thyroid profile.


2021 ◽  
Vol 100 (6) ◽  
pp. 617-622
Author(s):  
Natalya F. Kushnerova ◽  
Yury A. Rakhmanin ◽  
Tatiana V. Momot ◽  
Rufina I. Mikhailova ◽  
Irina N. Ryzhova ◽  
...  

Introduction. It was studied the lipid composition of the blood plasma of rats under the impact of a hyper cholesterol diet with a high fat load. It was carried out the prevention of disturbances in blood plasma biochemical parameters with a lipid complex from the tunic of the marine hydrobiont Halocynthia aurantium. Materials and methods. The experiment was carried outwith outbred male rats weighing 200 ± 3 g.The experimental model of a hyper cholesterol diet with a high fat load with the development of dyslipidemia was set up by feeding the animals with ahigh fat diet consisting of 2% cholesterol and 20% beef fat from the total diet. The animals were divided into the following groups of 10 rats each: group 1 - control (standard diet), group 2 - dyslipidemia (hypercholesterol diet with high fat load), group 3 - dyslipidemia + lipid complex from ascidia. Results. It was shown that the influence of the diet was accompanied by an increase in the amount of total lipids in the blood plasma of rats, cholesterol, low-density lipoproteins (LDL), as well as a decrease in total phospholipids and high-density lipoproteins (HDL), which is considered as an indicator of the formation of dyslipidemia. The contents of phospholipid lysofractions increased due to the activation of phospholipases. The amount of fatty acid esters and cholesterol esters decreased, which indicates the inhibition of esterification processes. The imbalance in the phospholipid spectrum of blood plasma occurred: the amount of metabolically active fractions required for the functioning of membrane-bound enzymes decreased. The addition of a lipid complex from the tunic of ascidian purple into the diet was accompanied by a pronounced prophylactic effect, which manifested itself in the normalization of the studied biochemical parameters. The lipid complex containing a wide range of “sea” phospholipids and polynonsaturated fatty acids of the n-3 type is an important basis for application as prophylactic in the conditions of a hypercholesterol diet with a high-fat load. Conclusion. Application of the lipidic complexes containing the “sea” lipids allocated from a tunic of the ascidian purple can be useful and perspective at a dislipidemiya and a hypercholesterolemia that will allow to carry out effective prevention of violations of metabolic reactions at influence of hyper high-calorie food.


2018 ◽  
Vol 99 (6) ◽  
pp. 936-941
Author(s):  
S V Moskalenko ◽  
I I Shakhmatov ◽  
Yu A Bondarchuk ◽  
O V Alekseeva ◽  
O M Ulitina

Aim. To study the reaction of hemostasis system to a single effect of hypercapnic hypoxia of maximum intensity in rats and possibility of correcting hemostasis disorders by means of a preliminary course of an antihypoxant - mexidol. Methods. The study involved sexually mature male rats (48 specimens) of the Wistar line with an average mass of 274.0 ± 32.0 g. The rats were kept on a standard diet, food and water were fed once a day between 10 and 11 hours. In the evening, animals underwent a single hypercapnic hypoxia in a special flow chamber. The state of hypercapnic hypoxia of maximum intensity was modeled at O2 content of 5.0 %, CO2 - 5.0 % during a single 20-minute exposure. As a training regimen, a 30-fold course of mexidol was used, the drug was administered intraperitoneally to rats at a dose of 50 mg/kg for 1.5 hours prior to exposure to hypercapnic hypoxia. Results. After a single exposure to hypercapnic hypoxia of maximum intensity, shortening of the onset of clot formation, an increase of alpha angle, and maximum clot density were recorded. Also, the clot formation time shortened and the maximum clot lysis index increased. With a single exposure to hypercapnic hypoxia of maximum intensity after the course of mexidol, a decrease in the maximum clot density was recorded. Conclusion. A single exposure to hypercapnic hypoxia of maximum intensity was characterized by a shift of hemostatic potential toward hypercoagulability along with fibrinolytic system activation. The course use of antihypoxant mexidol, preceding hypercapnic hypoxia of maximum intensity, significantly reduces the risk of clot formation.


2019 ◽  
Vol 100 (4) ◽  
pp. 642-649
Author(s):  
S V Moskalenko ◽  
I I Shakhmatov ◽  
I V Kovalev ◽  
K I Shakhmatova ◽  
V M Vdovin

Aim. To study the adaptation reactions of the hemostasis system to hypercapnic hypoxia of maximum intensity in rats subjected to preliminary multiple exposure to ethylmethylhydroxypyridine succinate and hypercapnic hypoxia of submaximal intensity. Methods. In the experiment, Wistar male rats (80 individuals) were used. Training cycles: 30-fold daily exposure to hypercapnic hypoxia of submaximal intensity (20 minutes — 9.0±0.5% O2, 7.0±0.5% CO2); administration of ethylmethylhydroxypyridine succinate (50 mg/kg) to animals for 30 days; combined effects of the two described modes. Tested experimental exposure was simulated as a single hypercapnic hypoxia of maximum intensity (20 minutes — 5.0±0.5% O2, 5.0±0.5% CO2) at the end of each of three 30-day training cycles. Results. Preliminary 30-day exposure to both isolated hypercapnic hypoxia of submaximal intensity and combined exposure to ethylmethylhydroxypyridine succinate contributes to hypocoagulation shift in the hemostasis system and reduces the level of the markers of pre-thrombotic state in response to a single hypercapnic hypoxia of maximum intensity. The state of the hemostasis system after 30-day cycle of isolated use of an antihypoxant is characterized by the inhibition of the vascular-platelet system of the hemostasis system and preserved hypercoagulation shifts in its plasma unit. The obtained results suggest that both preliminary isolated effect of hypercapnic hypoxia of submaximal intensity and the combined effect of hypercapnic hypoxia and ethylmethylhydroxypyridine succinate increase the resistance of the hemostasis system in experimental animals to acute hypercapnic hypoxia of maximum intensity compared to rats of the control group. This was confirmed by the inhibition of the vascular-platelet system, hypocoagulation in the plasma unit, decrease in the level of thrombotic readiness markers and increase in the anticoagulant activity of the blood system compared to the control. At the same time, isolated course administration of ethylmethylhydroxypyridine succinate did not cause the same amount of adaptive changes to maximum intensity hypercapnic hypoxia, since only platelet suppression of the hemostasis and hypocoagulation via the internal coagulation pathway were registered. Conclusion. Isolated exposure of hypercapnic hypoxia of submaximal intensity and its combined exposure with ethylmethylhydroxypyridine succinate increase the resistance of the hemostasis system to acute hypercapnic hypoxia of maximum intensity; isolated course administration of ethylmethylhydroxypyridine succinate does not cause the same amount of adaptive changes.


2019 ◽  
Vol 100 (4) ◽  
pp. 642-649
Author(s):  
S V Moskalenko ◽  
I I Shakhmatov ◽  
I V Kovalev ◽  
K I Shakhmatova ◽  
V M Vdovin

Aim. To study the adaptation reactions of the hemostasis system to hypercapnic hypoxia of maximum intensity in rats subjected to preliminary multiple exposure to ethylmethylhydroxypyridine succinate and hypercapnic hypoxia of submaximal intensity. Methods. In the experiment, Wistar male rats (80 individuals) were used. Training cycles: 30-fold daily exposure to hypercapnic hypoxia of submaximal intensity (20 minutes — 9.0±0.5% O2, 7.0±0.5% CO2); administration of ethylmethylhydroxypyridine succinate (50 mg/kg) to animals for 30 days; combined effects of the two described modes. Tested experimental exposure was simulated as a single hypercapnic hypoxia of maximum intensity (20 minutes — 5.0±0.5% O2, 5.0±0.5% CO2) at the end of each of three 30-day training cycles. Results. Preliminary 30-day exposure to both isolated hypercapnic hypoxia of submaximal intensity and combined exposure to ethylmethylhydroxypyridine succinate contributes to hypocoagulation shift in the hemostasis system and reduces the level of the markers of pre-thrombotic state in response to a single hypercapnic hypoxia of maximum intensity. The state of the hemostasis system after 30-day cycle of isolated use of an antihypoxant is characterized by the inhibition of the vascular-platelet system of the hemostasis system and preserved hypercoagulation shifts in its plasma unit. The obtained results suggest that both preliminary isolated effect of hypercapnic hypoxia of submaximal intensity and the combined effect of hypercapnic hypoxia and ethylmethylhydroxypyridine succinate increase the resistance of the hemostasis system in experimental animals to acute hypercapnic hypoxia of maximum intensity compared to rats of the control group. This was confirmed by the inhibition of the vascular-platelet system, hypocoagulation in the plasma unit, decrease in the level of thrombotic readiness markers and increase in the anticoagulant activity of the blood system compared to the control. At the same time, isolated course administration of ethylmethylhydroxypyridine succinate did not cause the same amount of adaptive changes to maximum intensity hypercapnic hypoxia, since only platelet suppression of the hemostasis and hypocoagulation via the internal coagulation pathway were registered. Conclusion. Isolated exposure of hypercapnic hypoxia of submaximal intensity and its combined exposure with ethylmethylhydroxypyridine succinate increase the resistance of the hemostasis system to acute hypercapnic hypoxia of maximum intensity; isolated course administration of ethylmethylhydroxypyridine succinate does not cause the same amount of adaptive changes.


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