Evaluation of the activity of antihypoxants with an isothiourea structure in a model of hypercapnic hypoxia with a shutdown of the cerebral hemispheres

2021 ◽  
Vol 19 (1) ◽  
pp. 55-63
Author(s):  
Vera V. Marysheva ◽  
Vladimir V. Mikheev ◽  
Petr D. Shabanov
Keyword(s):  
Acute Hypoxia ◽  
Life Time ◽  
The Body ◽  
Cerebral Hemispheres ◽  
Antihypoxic Activity ◽  
Hypoxic Episode ◽  
Hypoxia With Hypercapnia ◽  
Hypercapnic Hypoxia ◽  
Outbred Mice ◽  
The Brain

PURPOSE: To study the effect of amtizol, 2-aminobenzthiazole (2-ABT) and 2-amino-4-acetylthiazolo[5,4-b]indole (BM-606) on the resistance of male outbred mice to acute hypoxia with hypercapnia under conditions of isolated functioning of one from the hemispheres, as well as both hemispheres of the brain. METHODS: A model of acute hypoxia with hypercapnia (canned hypoxia) was used in mice of the same mass, the lifespan of all animals was determined. Temporary shutdown of the cortex of one of the hemispheres or both hemispheres was achieved by epidural application of filter paper moistened with 25% potassium chloride solution, creating a spreading depression according to Leao. Amtizol, 2-aminobenzthiazole (2-ABT) and 2-amino-4-acetylthiazolo[5,4-b]indole (BM-606) at equimolar doses of 25, 32.5, and 50 mg/kg, respectively were used as pharmacological analyzers, the compounds were injected intraperitoneally 30 min before the hypoxic episode. RESULTS: It was shown that, in contrast to amtizol, 2-ABT and VM-606 increase the life time of experimental animals when any hemisphere is turned off. The use of drugs when both hemispheres were turned off revealed that amtizol has approximately equal effect on the brain and the rest of the body, in 2-ABT antihypoxic activity is 1/3 associated with the brain, in VM-606 exclusively with the brain. CONCLUSION: The experimental model used in this work makes it possible to quite easily evaluate the effect of either one drug or compare several drugs, their role in the functioning of the cerebral hemispheres, on which part of the sample highly resistant or low resistant to hypoxia they have the greatest effect.

EFFECT OF AMINOTHIOL ANTIHyPOXANTS ON INTERHEMISPHERIC ASyMMETRy OF THE bRAIN

2012 ◽  
Vol 10 (1) ◽  
pp. 51-53
Author(s):  
Vladimir Vladimirovich Mihkeev ◽  
Vera Vasilievna Marysheva ◽  
Boris Nikolaevich Bogomolov ◽  
Lubov Vladislavovna Zhukova-Williams
Keyword(s):  
Left Hemisphere ◽  
Right Hemisphere ◽  
Acute Hypoxia ◽  
Life Time ◽  
Antihypoxic Activity ◽  
Interhemispheric Relations ◽  
Hypoxia With Hypercapnia ◽  
Antihypoxic Effect ◽  
The Right ◽  
The Brain

The effect of aminothiol antihipoxants amthizol and its analogue VM-606 on the resistance of the SHR mice males to an acute hypoxia with hypercapnia under conditions of isolated functioning of one of the hemispheres of the brain was studied. Antihypoxic agent amthizol 25 mg/kg increases life time of naïve mice by 46.2%. The drug acted on the sham-operated mice more slightly, increasing of their life only on 28.1% (p<0.01). Administration of amthizol under conditions of functioning of the right hemisphere significantly enhanced (+64.8%) the life time of mice. No antihypoxic effect was registered after administration of amthizol to mice with active left hemisphere: the result was the same as in mice without amthizol. Therefore, antihypoxic effect of amthizol was due to its action on the right (but not the left) hemisphere of the brain. VM-606 possessed more antihypoxic activity in comparison with amthizol. After unilateral cortical inactivation, VM-606 increased life time of mice both in active right and active left hemispheres, but in more degree in active right hemisphere. Thus, interhemispheric differences in resistance of mice to hypoxia with hypercapnia were diminished. Therefore, the differences between amthizol and VM-606 are the followings: amthizol inverts interhemispheric relations in hypoxia whereas VM-606 diminishes them.

scholarly journals Characteristics of external respiration of rats in acute hypercapnic hypoxia and its correction by new metal-complex antihypoxant

2014 ◽  
Vol 12 (2) ◽  
pp. 36-42
Author(s):  
Denis Vladimirovich Sosin ◽  
Andrey Viktorovich Yevseyev ◽  
Vitaliy Andreyevich Pravdivtsev ◽  
Petr Dmitriyevich Shabanov
Keyword(s):  
Metal Complex ◽  
Acute Hypoxia ◽  
Antihypoxic Activity ◽  
External Respiration ◽  
Low Oxygen ◽  
Resistance Level ◽  
Hypoxia With Hypercapnia ◽  
Hypercapnic Hypoxia ◽  
Low Oxygen Concentration ◽  
Respiration Parameters

Changes of external respiration parameters have been studied in experimental rats after oral introduction of new selenium-containing metal-complex substance πQ1983 in dose 100 mg/kg before and under action of acute hypercapnic hypoxia (AH+Hc). A substance for comparison was metabolic antihypoxant amthizole administered in similar way and dosage. The substances were 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 a respiration curve called pneumobarogramm (PBG) was recorded continually. It has been established that the substance πQ1983 decreases parameters of lungs ventilation in the rats. According to 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 respiratory system under hypercapnia action, twice longer life span of animals in hypoxic experiment, and by rising of possibility to withstand low oxygen concentration. It has been proved that the substance πQ1983 significantly surpass a substance for comparison amthizole in both antihypoxic activity and influence on external respiration parameters.

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

2016 ◽  
Vol 14 (1) ◽  
pp. 37-45
Author(s):  
Andrei V Evseev ◽  
Vitaliy A Pravdivtsev ◽  
Denis V Sosin ◽  
Marina A Yevseyeva
Keyword(s):  
Metal Complex ◽  
Electrical Activity ◽  
Respiratory System ◽  
High Resistance ◽  
Acute Hypoxia ◽  
Cardiorespiratory System ◽  
Resistance Level ◽  
Hypoxia With Hypercapnia ◽  
Hypercapnic Hypoxia ◽  
Complex Substance

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.

Central monoaminergic systems sensitivity to acute hypoxia with hypercapnia changes after the maintenance under the long-term social isolation

2018 ◽  
Vol 64 (6) ◽  
pp. 511-516 ◽  
Author(s):  
I.V. Karpova ◽  
V.V. Mikheev ◽  
V.V. Marysheva ◽  
N.A. Kuritcyna ◽  
E.R. Bychkov ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Social Isolation ◽  
Acute Hypoxia ◽  
Brain Structures ◽  
Hypoxia With Hypercapnia ◽  
Long Time ◽  
The Right ◽  
The Brain ◽  
Monoamines And Their Metabolites

The experiments were performed in male albino outbred mice kept in a group and under the conditions of long-term social isolation. The changes in the monoaminergic systems of the left and right hemispheres of the brain after acute hypoxia with hypercapnia have been studied. The levels of dopamine (DA), serotonin (5-HT) and their metabolites – dioxyphenylacetic (DOPAC), homovanillic (HVA), and 5-hydroxyindoleacetic (5-HIAA) acids – were determined by HPLC in the cerebral cortex, hippocampus and striatum of the right and left sides of the brain. In the control mice kept both in the group and under the conditions of social isolation, a higher content of DA in the cortex of the left hemisphere has been found. In the other brain structures the monoamine content was symmetric. In the cerebral cortex of the mice in the group, acute hypoxia with hypercapnia led to a right-sided increase in the DA and 5HT levels. At the same time, the DOPAC content decreased in the left cortex. In mice in the group, under the hypoxia with hypercapnia conditions, the DA level in the left hippocampus increased. In the striatum, the content of monoamines and their metabolites did not change significantly. In animals kept for a long time under the conditions of social isolation, hypoxia with hypercapnia no statistically significant changes in the monoamines and their metabolites levels were found. It has been concluded that the preliminary maintenance under the conditions of prolonged social isolation changes the reaction of central monoaminergic systems to acute hypoxia with hypercapnia.

scholarly journals The influence of new coumarin derivatives on survival rate of mice in model conditions of acute hypoxia

2020 ◽  
Vol 19 (4) ◽  
pp. 103-108
Author(s):  
Olga M. Rodionova ◽  
Albina F. Safonova ◽  
Anton O. Kashirin ◽  
Valeriy A. Polukeev ◽  
Eugenii R. Bychkov ◽  
...  
Keyword(s):  
Survival Rate ◽  
Sodium Nitrite ◽  
Acute Hypoxia ◽  
Life Time ◽  
Distilled Water ◽  
Coumarin Derivatives ◽  
Test Compound ◽  
Hypoxia With Hypercapnia ◽  
Positive Effect ◽  
Histotoxic Hypoxia

Objective. The article is devoted to study the anti-hypoxemic properties of new coumarin derivatives in the models of hypoxemic hypoxia with hypercapnia, hemic hypoxia and histotoxic hypoxia. Materials and methods. Нypoxemic hypoxia with hypercapnia was modeled as follows: mice were placed in hermetic 200 cm3 jars one in a jar. Hemic hypoxia was reproduced in mice by single subcutaneous introduction of sodium nitrite in a dose of 230 mg/kg. Histotoxic hypoxia was caused in mice by intraperitoneal introduction of sodium nitroprusside in a dose of 20 mg/kg. Coumarin derivatives under lab codes IEM-2266 and IEM-2267 were dissolved in distilled water with addition of twin-80, and then a single intraperitoneal infusion of them in doses 25 and 50 mg/kg was made 45 minutes before placing to the model conditions. Increased life time of an animal compared with the control served the criterion of anti-hypoxemic effect of the studied substances. Results. In hypoxemic hypoxia with hypercapnia test compound under IEM-2267 in doses of 25 and 50 mg/kg increased mice life time by 26 and 34% respectively in comparison with control. In hemic hypoxia model, the positive effect was seen with IEM-2266 compound in a dose of 50 mg/kg which increased life time of animals by 45% in comparison with control. In histotoxic hypoxia model, at preventive introduction of IEM-2266 compound in a dose of 25 mg/kg and IEM-2267 in a dose of 50 mg/kg life time increased up to 117% and 123% respectively. Conclusion. The coumarin derivatives IEM-2266 and IEM-2267 relieved the course of acute hypoxia and increased life time of animals in the models of hypoxemic hypoxia with hypercapnia, hemic hypoxia and histotoxic hypoxia.

scholarly journals MECHANISMS OF ANALEPTIC AND ANTIGYPOXIC EFFECTS OF HETEROSIDES - DERIVATIVES OF SULFUR AND NITROGEN-CONTAINING HETEROCYCLES

2019 ◽  
pp. 46-53
Author(s):  
I. V. Kabachna ◽  
V. I. Kabachnyy ◽  
S. M. Drohovoz
Keyword(s):  
Theoretical Basis ◽  
Behavioral Responses ◽  
Antihypoxic Activity ◽  
Sodium Thiopental ◽  
Experimental Reproduction ◽  
The Awakening ◽  
Hypoxia With Hypercapnia ◽  
Derivatives Of ◽  
The Brain ◽  
Detoxification Mechanisms

In order to expand the theoretical basis of the purposeful search of analeptics, the awakening and antihypoxic properties of heteroside-21, heteroside-31 (derivatives of sulfur- and nitrogen-containing heterocycles) were studied and the mechanisms of their action were established. Sodium thiopental (42 mg/kg) was used to simulate suppression of the respiratory and vascular centers of the brain. The comparison drugs were – sulfocamphocaine (SCC) with combined analeptic action (20 mg/kg) and the antihypoxic drug piracetam (300 mg/kg). The results were obtained on the models of thiopental anesthesia and normobaric hypoxia with hypercapnia. The analysis of data allowed to count qualitatively and quantitatively the arousing and antihypoxic activity of new substances and classical drugs; their effect on the respiratory center of the brain and behavioral responses of animals; theoretically substantiate, experimentally confirm and establish aerobic, anaerobic and detoxification mechanisms of realization of effects in various conditions; to formulate the theoretical bases of purposeful search of universal analeptics and antihypoxic drugs and offer an instrumental-methodological complex for their experimental reproduction.

scholarly journals II-Valent metals complex compounds and prospects of the acute hypoxia protection

2019 ◽  
Vol 17 (1) ◽  
pp. 53-56
Author(s):  
Andrey V. Evseev ◽  
Albert E. Belenky ◽  
Dmitrij V. Surmenev ◽  
Marina A. Evseeva ◽  
Denis V. Sosin
Keyword(s):  
Protective Effect ◽  
Rectal Temperature ◽  
Active Substance ◽  
Acute Hypoxia ◽  
Complex Compounds ◽  
Antihypoxic Activity ◽  
Reference Substance ◽  
Divalent Metals ◽  
Hypoxia With Hypercapnia ◽  
Antihypoxic Effect

Aim. To find antihypoxic properties in complex compounds of some divalent metals on the model of acute hypoxia with hypercapnia. Methods. In the experiments on mice in acute hypoxia with hypercapnia (AH+Hc), the protective effect of 6 new complex compounds was studied in comparison with the effectiveness of reference antihypoxants. Substances were injected intraperitoneally 60 min before acute hypoxia with hypercapnia in doses of 25 and 50 mg/kg. Antihypoxic effect was compared with their ability to change the rectal temperature. Results. The most active substance πQ-2116 with Nickel as a complexing metal was established. Mice resistance to acute hypoxia with hypercapnia at a dose of 25 mg/kg was increased to 89.5%, at a dose of 50 mg/kg – to 165.8%. The effect was accompanied by serious hypothermia, reaching 28.5 °C. Antihypoxic activity of the substance πQ-2116 is comparable with reference substance πQ-1983 and greater than the effect of aminothiol antihypoxants – Amtizole and Sunazole.

scholarly journals The time course of changes in the state of monoaminergic systems in the brain of mice under the acute hypoxia with hypercapnia

2019 ◽  
Vol 65 (6) ◽  
pp. 485-497
Author(s):  
I.V. Karpova ◽  
V.V. Mikheev ◽  
V.V. Marysheva ◽  
N.A. Kuritcyna ◽  
E.R. Bychkov ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Time Course ◽  
Acute Hypoxia ◽  
Control Level ◽  
Hypoxic Exposure ◽  
Negative Consequences ◽  
Metabolite Level ◽  
Hypoxia With Hypercapnia ◽  
The Right ◽  
The Brain

In socially isolated male outbred albino mice, the changes of monoaminergic systems under acute hypoxia with hypercapnia were studied. In cerebral cortex, hippocampus and striatum of the right and left sides of the brain, the concentrations of norepinephrine, dopamine, serotonin and their metabolites – dihydroxyphenylacetic, homovanillic and 5-hydroxyindoleacetic acids were investigated using the HPLC method. In isolated mice, which were not subjected to hypoxia with hypercapnia, higher levels of dopamine and serotonin in the left cortex were found. There was no asymmetry in monoamines and their metabolites in other studied brain structures. 10 min after the onset of exposure, acute hypoxia with hypercapnia resulted in a right-sided increase in norepinephrine levels and a decrease in dopamine levels in the striatum and serotonin levels in the hippocampus. In the cerebral cortex, 10 min after of hypoxic exposure beginning, there was a left-sided decrease in the dopamine content, while the original asymmetry found in the cortex of intact animals disappeared. In isolated mice perished of hypoxia with hypercapnia, almost all parameters returned to the control level. The exception was the ratio of serotonin metabolite level to the neurotransmitter, which in the right cortex became lower than in control animals. In white outbred mice, the brain monoaminergic systems are suggested to be relatively resistant to the negative consequences of hypoxia and hypercapnia, and corresponding shifts resulting in the reflex brain response to changes in the gas composition of the respiratory air.

scholarly journals The effect of acute hypoxia with hypercapnia on the content of monoamines in symmetrical areas of the brain in albino mice

2018 ◽  
Vol 64 (3) ◽  
pp. 257-260 ◽  
Author(s):  
I.V. Karpova ◽  
V.V. Mikheev ◽  
V.V. Marysheva ◽  
N.A. Kuritcyna ◽  
N.A. Popkovskii ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Brain Cortex ◽  
Acute Hypoxia ◽  
Other Substances ◽  
Hypoxia With Hypercapnia ◽  
Left And Right ◽  
Albino Mice ◽  
The Right ◽  
The Brain ◽  
Monoamines And Their Metabolites

Changes in the activity of monoaminergic systems of the left and right hemispheres of the brain after acute hypoxia with hypercapnia were investigated in male albino mice. The concentrations of dopamine (DA), serotonin (5-HT) and their metabolites dihydroxyphenylacetic (DOPAC), homovanilic (HVA) and 5-hydroxyindolacetic (5-HIAA) acids were measured by HPLC in the brain cortex, hippocampus and striatum of the right and the left hemispheres. In the control mice not exposed to hypoxia with hypercapnia, a higher concentration of DA in the left cortex was detected. No asymmetry in the content of other substances has been identified in the investigated structures. Acute hypoxia with hypercapnia led to the right-sided increase of DA and 5-HT levels and to the left-sided reduction DOPAC in the cerebral cortex. Under the condition of hypoxia with hypercapnia, in the hippocampus, the left-sided increase of the DA content was revealed. In the striatum the contents of monoamines and their metabolites were insignificantly changed. It has been concluded that acute hypoxia with hypercapnia causes asymmetric changes in monoaminergic systems of the archicortex and the neocortex.

scholarly journals Effect of acute hypoxia with hypercapnia on the content of monoamines in symmetrical brain structures of the BALB/c male mice

2014 ◽  
Vol 60 (2) ◽  
pp. 258-263 ◽  
Author(s):  
I.V. Karpova ◽  
V.V. Mikheev ◽  
V.V. Marysheva ◽  
E.R. Bychkov ◽  
P.D. Shabanov
Keyword(s):  
Brain Cortex ◽  
Acute Hypoxia ◽  
Brain Structures ◽  
Serotonin Level ◽  
Dopamine Level ◽  
Male Mice ◽  
Left Brain ◽  
Hypoxia With Hypercapnia ◽  
The Right ◽  
The Brain

The changes in activity of monoaminergic systems of both the right and the left brain hemispheres of the BALB/c male mice after an acute hypoxia with hypercapnia were studied. The concentrations of dopamine, serotonin and their metabolites dihydroxyphenylacetic, homovanilic and 5-hydroxyindolacetic acids were measured by HPLC in the brain cortex, hippocampus and striatum of the right and the left hemispheres. The more high concentration of serotonin was revealed only in the cortex of the left hemisphere in control mice without hypoxia with hypercapnia. The asymmetry in dopamine level was not registered in all structures studied. Acute hypoxia with hypercapnia decreased the dopamine level in the striatum and the serotonin level both in the hippocampus and the brain cortex. The dopamine metabolites level was reduced in the striatum and in the brain cortex of hypoxed mice: both metabolites in the right brain cortex and only dihydroxyphenylacetic acid in the left brain cortex. Serotonin metabolism was decreased in all brain structures studied after hypoxia with hypercapnia in mice. Therefore, serotoninergic system of the brain is more sensitive to acute hypoxia with hypercapnia than dopaminergic system.

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