scholarly journals Therapeutic effect of thiocetam on the manifestations of ischemia-reperfusion complicated by massive blood loss and mechanical trauma

2020 ◽  
Vol 10 (12) ◽  
pp. 382-393
Author(s):  
Nataliya Volotovska

Among the current medical and social problems, injuries and blood loss occupy a prominent place, causing stress on the antioxidant defenses. Hypoxia, which underlies the pathogenesis of the post-traumatic period of both diseases, leads to a significant imbalance in the work of internal organs. Scientists are increasingly attracted by the need to use a tourniquet or intraoperative ligatures, as reperfusion local and systemic damage develops. Antioxidants are considered a promising means of correction.The aim of the study was to investigate the features of metabolic disorders in the liver in the early post-traumatic period on the background of the use of a tourniquet and the effectiveness of thiocetam correction.Materials and methods. The experiment was perfomed on 130 white male rats (200-250 g), which were divided into 4 groups: control – the CG, the EG-1 – combination of limb ischemia-reperfusion (IR) with blood loss, the EG-2 – combination of limb IR with blood loss and mechanical trauma of the thigh; the EG-3 combination of limb IR, blood loss, mechanical injury and thiocetam administration. The Malonic dialdehide level catalase activity were estimated in the liver.Results. The use of thiocetam, which is able to struggle against of ischemia and lipid peroxidation by reactivating antiradical enzymes: superoxide dismutase, catalase and glutathione peroxidase, had a positive effect on the state of antioxidant and prooxidant units in the organ, located far from the place of primary ischemia-reperfusion. If in the group of untrated animals (the EG-2, where massive blood loss was combined with a thigh fracture and the use of hemostatic tourniquet) in the early period, the MDA level exceeded the CG data in 5,4 times, and on the 7th and 14th days remained high – being higher on 2,1 times and on 2,7 times, then in the EG-3 (group of treated animals) on the 1st day the level of MDA exceeded the CG data in 4,3 times, but on the 7th and 14th days was higher by 90,5 % and 64 % respectively. The supportive effect of thiocetam on the activity of catalase in the liver was also noted. Thus, in EG-2 the level of antioxidant enzyme on the 1st day decreased by 71,7 %, and remained almost at this level throughout the all post-experimental period. As for the group of treated animals, the level of activity on the 1st day after the intervention decreased by 44,7%, and was so for almost the entire period. On the 14th day, it remained reduced compared to the CG by 35,1 %, while in EG-2 this index was lower compared to the CG by 70,5 %.Conclusion. Having the positive effect of the introduction of thiocetam in the ischemic area, we can eventually add new complex, given the world experience, which would affect the development of the inflammatory response and the rheological properties of blood.

2021 ◽  
pp. 24-30
Author(s):  
Nataliya Volotovska

The use of hemostatic tourniquet is a proved means of primary care. However, systemic disorders, as well as ultrastructural, in the area of compression can significantly worsen the condition of the injured organism. The aim. Estimation of catalase level in rats’ liver on the background of modifications of ischemic-reperfusion syndrome to know the severest pathogenic combination for organism. Materials and methods. 260 white adult male rats were divided into 5 groups: control (KG), EG1 – simulation of isolated ischemia-reperfusion syndrome (IRS) of the limb, EG2 – simulation of isolated volumetric blood loss, EG3 – combination of IRS of the limb with blood loss, EG4 – simulation of isolated mechanical injury of the thigh, EG5 – combination of IRS of the limb and mechanical injury. The variability of catalase level in liver was analyzed. Results. It was found that each of the experimental interventions has led to changes of catalase activity in the liver. The most expressed pathological expressions were observed on the 3rd after interventions, when the studied index in EG3 was lower than in EG1 and EG2 in 6,2 times and by 33,1 %. On the 7th day catalase activity in EG3 was in 9,4 times and by 44,5 % times lower than in EG1 and in EG2 data concordantly. The combination of limb ischemia-reperfusion with blood loss in EG3 led to exhausting of liver antioxydant enzyme catalase in the most critical posttraumatic period (day 3). The same, but less significant effect was registered in the group of combination of mechanical trauma with ischemia-reperfusion in EG5. This proved the role of the tourniquet as a factor that complicated the course of traumatic disease due to ischemic reperfusion. Conclusions. In this experiment, founded risk factors of combination of ischemia-reperfusion with heavy blood loss emphasized the importance and particular attention on such widespread method of bleeding tratment, as the imposition of a tourniquet, as in our experiment it triggered risk factors of ischemia-reperfusion. It was shown katalase activity depression respectively to the periods of increasing of lipid peroxydation. There was peculiarity, that on the base of isolated IRS catalase activity was increased in 2,5 times comparely to control group, whereas the hardest depression of it was found on the background of IRS, combined with blood loss – catalase activity was lower, comparely to KG – in 2,5 times. The importance of understanding the suppression of hepatocytes’ antyoxydants is great, as it might help in prevention the development of liver failure or hepatorenal syndrome on the background of limb ischemia-reperfusion.


Author(s):  
N. V. Volotovska ◽  
A. A. Hudyma

Nowadays stop the bleeding and fight against its consequences determines further success in the survival and rehabilitation of the victim. It is extremely important to find ways to improve the ischemic metabolism as a result of overlaying a tissue turnstile. Enzymes of the glutathione system are actively involved in combating the effects of hypoxia, therefore, the experimental detection of critical periods of depression of this protectional link is the basis for the further search for effective methods of correction and condition stabilization of the affected organism.The aim of the study – to determine the role of glutathione system of the liver and kidneys in the pathogenesis of experimental ischemia-reperfusion (EIR) in the early and remote post-traumatic periods.Materials and Methods. The object of the study – 196 males of white male rats with a body weight 220–240 g, divided into 4 groups, 10 individuals in each. Animals of the control group were withdrawn from the study without surgical intervention, while in the experimental groups, injuries were simulated: a hemostatic tourniquet on the thigh (J) over two hours; isolated blood loss from the femoral vein (40%) – (K); two-hour ischemia, combined with blood loss (J + K) and two-hour ischemia, combined with blood loss and mechanical trauma (J + K + P). The animals were withdrawn from the experiment at 1, 3, 7 and 14 days after the intervention by total bleeding from the heart.Results and Discussion. According to the activation of the lipid peroxidation, which was represented by the growth of the concentration of malonic dialdehyde, diene and trienic conjugates, an active response from the glutathione system was detected: the activation of glutathioneperoxidase activity, an increase of glutathionereductase activity against the decrease restored glutathione concentration. But in the kidney tissue the activity of glutathione system enzymes was somewhat lower, herewith in some periods, conversly, they exceeded liver parameters. These results, in our opinion, indicate that the reason of such their dividing, mainly, it is total debilitation of the glutathione system in the posttraumatical period. It was 1 and 3 days after trauma and partly depended of the injury severity. At the same time, even an isolated overlay of the hemostatic tourniquet led to significant changes of the glutathione system and was represented by response to the activation of lipid peroxidation. This confirms the necessity to continue the series of experiments.Conclusions. The obtained results of the experiments revealed a significant inhibition of the reduced glutathione concentration in the liver, and no so expressed in the kidneys. Especially depression of its activity was on the background of bleeding associated with ischemia, and bleeding associated with ischemia and mechanical trauma. Decrease of glutathioneperoxidase and glutathionereductase activity coincided with increase of lipid peroxidation.


Author(s):  
N. V. Volotovska ◽  
T. V. Kashchak

Background. Blood loss during civil and military limb trauma is the most common cause of preventable death. Complications due to the use of a hemostatic tourniquet are widely investigated nowadays. Therefore, the standards of the past have to be improved. Objective. The aim of the research is to study the reaction of the enzyme chain of the liver antioxidant system in the presence of modifications of ischemia-reperfusion injury (IRI). Methods. 210 white male-rats, aged 5-5.5 months, were used in the research. The dynamics of antioxidant enzymes activity catalase (Cat) and superoxide dismutase (SOD) in liver tissue in cases of modifications of ischemia-reperfusion injury (IRI) were studied. The period of investigation was in 24 hours, 3, 7, 14 days after the injury. Results. In cases of simulated IRI the catalase level mainly decreased at each period of the experiment. The peak of SOD activity was evidenced on the 1st, 3rd or 7th days after the experimental IRI according to the degree of trauma severity. Thus, IRI combined with severe blood loss and mechanical trauma caused the severest affection of the antioxidant system. Even a single application of hemostatic tourniquet caused similar wavelike reactions at different times. Conclusions. The development of IRI is accompanied by a significant depression of the liver antioxidant system. The most significant changes were evidenced in cases of IRI combined with blood loss and mechanical trauma, but even a single application of a tourniquet caused active response of the antioxidant enzymes.


Author(s):  
T. A. Zaiets ◽  
T. V. Boiko ◽  
S. V. Dzyha ◽  
H. H. Habor

The aim of the work. To find out the dynamics of indicators of biligenic function of the liver in response to cranial skeletal trauma associated with haemorrhage. Materials and Methods. Experiments were performed on 54 outbred white male rats, weighing 180–200 g. Animals were divided into three groups: a control one and two experimental. Closed cranio-skeletal injury according to the established technique in our own modification was mo­delled under thiopental-sodium anaesthesia. A single hit on each hip that caused a closed fracture of femoral bones, was performed by means of an individually designed device. The striking force was 0.375 J, which corresponded to a moderate injury. Results and Discussion. It has been first established that the complication of cranio-skeletal trauma with additional blood loss exa­cerbates and accelerates liver dysfunction. The content in bile of total bile acids, cholesterol, the degree of conjugation of bilirubin, the rate of biliary excretion and excretion of the main components of bile, as well as absorption-excretory and glycogen synthesizing functions are impaired already on the first day of the post-traumatic period and in all times of the follow-up period they significantly differ from the similar indices of the injured animals with no blood loss. Conclusions. In the presence of experimental cranio-skeletal trauma, the rates of liver biligenic function change up to a maximum declination in 7 days of post-traumatic period. Additional haemorrhage intensifies the revealed abnormalities: the content of total bile acids and cholesterol in bile, as well as the amount of direct bilirubin and the degree of its conjugation in post-traumatic period are significantly lower during the whole period of observation.


Author(s):  
А.В. Ефремов ◽  
Т.П. Храмых ◽  
Н.В. Говорова ◽  
П.А. Ермолаев

Введение. Ведущим патогенетическим фактором массивной кровопотери является гипоксия, инициирующая активацию процессов свободнорадикального окисления (СРО) в органах и тканях и системный воспалительный ответ. Показано, что одним из универсальных звеньев формирования множественной органной дисфункции при кровопотере является изменение проницаемости кишечной стенки с транслокацией микрофлоры и токсинов в системный кровоток на фоне реперфузии. В последнее время внимание исследователей привлекает эффект анестетического прекондиционирования, в том числе при операциях, сопровождающихся геморрагической гипотензией (ГГ). Цель исследования - оценка в эксперименте динамики процессов СРО в тонкой кишке при геморрагической гипотензии на фоне применения анестетика севофлурана, обладающего эффектом анестетического прекондиционирования. Методика. Эксперименты проведены на 105 белых крысах-самцах. ГГ моделировали, используя в 1-й группе в качестве анестетика эфир во 2-й - анестетик севофлуран. Контролем служили 2 группы интактных животных: одна - с эфиром, другая - с севофлураном. Для оценки процессов СРО через 15 мин, 30 мин, 1 ч, 2 ч ГГ забирали фрагменты тонкой кишки. Исследование хемилюминесценции (ХЛ) гомогенатов тонкой кишки проводили по методу Р.Р. Фархутдинова, используя хемилюминомер “Флюорат АБЛФ-2Т”. Регистрировались показатели СРО: спонтанная светимость (СС), вспышка (В), светосумма (С∑). Результаты. Через 15 мин ГГ (2-я группа,. севофлуран) обнаружено повышение показателя СС в тощей кишке на 33%; снижение показателя В в 12-пк в 2 раза, в тощей и подвздошной кишке - на 24 и 36% соответственно. Показатель С∑ снижался в 12-пк на 36%, в тощей и подвздошной кишке - на 45% и 52% соответственно по сравнению с 1-й группой (эфир). На 30-й мин показатель СС в тощей кишке повышался на 80%. На фоне ГГ при применении севофлурана отмечено снижение показателя В в 12-пк на 38%, в тощей кишке на 22%, а в подвздошной в 3 раза. Через 1 ч ГГ при использовании севофлурана наблюдалось повышение СС в в тощей кишке в 2 раза, в 12-пк и подвздошной - на на 38% и 15% соответственно. Показатель В снижался в 12-пк на 67, в тощей - на 43%; Показатель С∑ в 12-пк и тощей кишке снижался в 2,6 и 2,5 раза, в подвздошной - на 70% по сравнению с группой «эфир». Через 2 ч ГГ в группе «севофлуран» обнаружено увеличение СС в тощей и подвздошной кишках на 80% и в 3 раза, соответственно, по сравнению с эфирным наркозом. При этом наблюдалось уменьшение С∑ в 12-п и тощей кишке - на на 24% и 15% соответственно. Заключение. На фоне ГГ наблюдается активация процессов СРО в тонкой кишке при использовании эфира; прекондиционирование анестетиком севофлураном способствовало значительному ограничению окислительного стресса в тонкой кишке крыс возможно за счет активации антиоксидантной системы. Introduction. The major pathogenetic factor of massive blood loss is hypoxia, which triggers activation of free-radical oxidation (FRO) processes in organs and tissues and the systemic inflammatory response. A universal factor of multiple organ dysfunction in blood loss is altered intestinal wall permeability with translocation of microflora and toxins into the systemic circulation during reperfusion. Recently, much of the attention has been focused on effects of anesthetic preconditioning, including during operations associated with hemorrhagic hypotension (HH). The aim of this study was to evaluate in experiment the dynamics of small intestinal FRO in HH during the use of the anesthetic sevoflurane, which has an effect of anesthetic preconditioning. Methods. Experiments were performed on 105 white male rats divided into two groups; groups 1 and 2 were exposed to HH with ether or sevoflurane as the anesthetic, respectively. Two groups of intact animals treated with ether or sevoflurane were used as the controls. Five animals died during the experiment. To evaluate FRO processes, samples of the duodenum, jejunum, and ileum were taken at 15 min, 30 min, 1 h, and 2 h of HH. The chemiluminescence (CL) study of small intestine homogenates was performed according to the Farukhutdinov method on a Fluorate ABLF-2T chemiluninometer. The following FRO indexes were recorded: spontaneous luminosity (SL), flash (F), and light sum (L∑). Significance of differences was determined with the Mann-Whitney test. Results. In the sevoflurane group 2 compared to the ether group after 15 min of HH, SL was increased in the jejunum by 33%; F was decreased in the duodenum by 50%, in the jejunum by 24%, and in the ileum by 36%; L∑ was decreased in the duodenum by 36%, in the jejunum by 45%, and in the ileum by 52%. At 30 min, SL in the jejunum was increased by 80%. In the HH+sevoflurane group, F was decreased in the duodenum by 38%, in the jejunum by 22%, and in the ileum by 27%; L∑ in the duodenum was decreased by 44%, in the jejunum by 45%, and in the ileum by 67%. After 1 h of HH+sevofluran, SL was increased in the jejunum twofold, in the duodenum by 38% and in the ileum by 15%; F was decreased in the duodenum by 67% and in the jejunum by 43%; L∑ in the duodenum was decreased by 62%, in the jejunum by 60%, and in the ileum by 70% compared to the ether group. After 2 h of HH+sevofluran, SL was increased in the jejunum and ileum by 80% and 67%, respectively, compared to the ether group. In this process, L∑ in the duodenum was decreased by 24% and in the jejunum by 15%. Conclusion. The HH+diethyl ether exposure was associated with activation of FRO processes in the small intestine. The sevoflurane preconditioning provided a significant restriction of oxidative stress in the rat small intestine due to activation of the antioxidant system in the duodenum, jejunum, and ileum at 1 h, 15 min, and 30 min of HH, respectively.


2021 ◽  
Vol 11 (5) ◽  
pp. 229-236
Author(s):  
I. V. Kuzminskyi ◽  
V. K. Grodetskyi ◽  
H. Yu. Thymbalyuk

The function of the organs responsible for detoxification processes, in particular the liver, deserves a special role in the conditions of combined trauma. It is proved that ischemia-reperfusion of the limb caused by the imposition of a tourniquet, is the cause of significant toxemia. Under such conditions, it becomes clear that the detoxification function may be impaired, especially against the background of blunt combined trauma to the abdominal organs complicated by massive bleeding. Changes in the detoxification function of the liver are indicated by markers of the cytolytic syndrome. However, there is no clear understanding of how ischemia - limb reperfusion affects the development of cytolytic syndrome.Objective of research: to study the effect of massive blood loss associated with ischemia-reperfusion of the limb on the cytolytic syndrome indicators in case of injury of the abdominal organs.  Materials and methods. 100 mature albino male Wistar rats with the body weight of 190-220 grams kept on standard vivarium forage were used in the experiment. The animals were divided into the control and 3 research groups (containing 10 animals each). Arresting bleeding tourniquet was applied proximally on the lower limbs of rats from the first research group for 120 minutes under thiopental-sodium anesthesia (40 mg/kg-1), which caused development of ischemic-reperfusion.  Closed abdominal injury was simulated by means of delivering two dosed blows in the region of the abdominal cavity in the second research group; massive blood loss was simulated by means of cutting the femoral vessels and bloodletting from 25 to 30 % of the circulating blood volume in the group. Injuries from the first two groups were combined in the third group. The control group of animals received anesthesia without formation of any injuries. With the aim to determine alterations of cytolytic syndrome the activity of enzymes – markers of cytolytic syndrome ALT and AST were determined by means of a unified method.  The animals of the research groups were removed from the experiment under thiopental-sodium anesthesia by means of the total bloodletting from the heart.Results. Analysis of the results of the study found that cytolytic syndrome develops irrespective of the kind of injuries simulated. Thus, even during a day of post-traumatic period ALT and AST activity increases which is clearly registered in all the three research groups. Further destruction of cellular membranes increases till the 3rd day, which is manifested by a considerable increase of ALT and AST activity in the blood serum. This process continues till the 7th day. A tendency to ALT and AST decrease is observed only in the 1st group on the 7th day. Comparison of the 2nd and 3rd research groups within the time interval enables to understand that application of tourniquets on the limbs of animals with closed abdominal injury and massive bleeding deteriorates cytolytic processes.Conclusions: Simulated injuries in the research groups were associated with the occurrence of cytolytic processes possessing a tendency to develop in the period of early signs of traumatic disease.  Ischemic-reperfusion syndrome of the limbs accelerates considerably the development of systemic changes with abdominal injuries and hypovolemic shock, which was manifested by a considerable increase of ALT and AST parameters in the group with abdominal trauma and massive blood loss and becoming higher than that of the control in end of the experiment.


2020 ◽  
Vol 210 ◽  
pp. 06014
Author(s):  
Anatoly Devyatkin ◽  
Olga Pavlova ◽  
Olga Gulenko ◽  
Pavel Boriskin

Hemato-ophthalmic barrier protects nervous system tissues from adverse factors. Against the background of inflammatory process caused by mechanical trauma of the eye, large molecules are able to penetrate the eyeball. At present, the mechanism of restoring the homeostatic balance of the body under oxidative stress caused by mechanical trauma of the eye is poorly studied. The aim of the study was to study the dynamics of catalase activity in rat brain tissue under oxidative stress caused by mechanical influence on hemato-ophthalmic barrier. Materials and methods: the study was conducted on white male rats of six months of age in the amount of 150 pieces. The activity of catalase in brain tissue was studied before the experiment, as well as on the 1st, 3rd, 5th, 7th and 14th day of the experiment using the standard Korolyuk M.A. method. The obtained digital material was statistically processed by non-parametric statistical analysis. Conclusion: The activity of catalase in the rat brain under oxidative stress caused by mechanical action on the hemato-ophthalmic barrier is most effectively stabilized in the standard therapy of mechanical eye injury with the addition of quercetin in the form of injections.


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