scholarly journals The effect of cranioskeletal trauma complicated by blood loss on the functional state of the liver in the early period of traumatic disease in rats with different resistance to hypoxia and their correction

2021 ◽  
Vol 11 (2) ◽  
pp. 256-269
Author(s):  
D. O. Sikirynska ◽  
A. A. Hudyma ◽  
A. H. Shulhai ◽  
K. A. Pokhodun

Introduction. Traumatic events are considered to be one of the current problems in modern urban society. Beyond being the immediate cause of the death of the injured, the development of multiple organ failure syndrome is a perilous complication of severe multiple and combined trauma. An experimental cranioskeletal trauma is known to be accompanied by internal organ dysfunction. Nonetheless, the development of organ dysfunction in terms of hypoxia resistance in the presence of cranioskeletal trauma remains insufficiently studied.The objective of research: to establish the dynamics of the functional state of the liver in the presence of cranioskeletal trauma, complicated by blood loss in rats with different hypoxia resistance in the early period of traumatic disease and evaluate the efficacy of Thiocetam in the correction of identified abnormalities.Material and methods: The experimental studies were conducted on 196 white non-linear male rats weighing 180-200g. Initially, an individual resistance to hypoxia of the rats was estimated, and the animals demonstrated high- and low- resistance value to hypoxia (HR and LR, respectively) were selected for the further study. The HR- and LR-rats were separately divided into 4 groups: control and three experimental once. In the first experimental groups the HR-and LR-animals were induced the cranioskeletal trauma under thiopental sodium anesthesia (40 mg·kg-1); the animals of the second experimental groups were inflicted the acute blood loss of 20-22% of circulating blood volume; in the third experimental groups, the HR and LR animals were subjected to an acute blood loss following the cranioskeletal trauma and administered the intraperitoneal injection of the Thiocetam at a dose of 250 mg·кg-1 of body weight once a day for correction. The bile excretion function of the liver was analyzed in the controls and experimental groups of animals 1, 3 and 7 days after trauma.The results and discussion. The conducted studies indicated the higher rate of bile excretion in the control group of LR-rats compared to the control of HR-rats. The rate of bile excretion was occurred decreased in both HR- and LR-rats under the influence of the cranioskeletal trauma. However, the degree of decrease in the studied parameter of the LR-rats was considerably greater than the corresponding value of the HR-rats. An additional blood loss model resulted in more marked abnormalities, particularly in the experimental group of LR-rats. The 7-day administration of Thiocetam led to the significant decrease in the abnormal bile excretion rate in the experimental groups of HR- and LR-rats compared to the animals without corrective medication. The analysis of deviation degree of the studied parameter in the animals administered Thiocetam in relation to the animals without correction evidenced better efficacy of the medication in the experimental group consisted of LR-rats compared to the group of HR-rats, especially under the conditions of additional acute blood loss model. Consequently, Thiocetam is able to compensate less-developed defense mechanisms of LR-rats compared to the HR-rats, which should be taken into consideration in real-life clinical practice settings in the comprehensive treatment of the injured with cranioskeletal trauma complicated by blood loss considering the possibility to determine their resistance to hypoxia.Conclusions. The rate of bile excretion as a basic indicator of the functional state of the liver in the intact LR-rats is found to be substantially higher than in HR-rats. The degree of decrease in the rate of bile excretion is significantly greater in LR-rats after 7 days of the post-traumatic period under the influence of cranioskeletal trauma complicated by acute blood loss. The administration of Thiocetam is accompanied by a marked positive effect on the rate of bile excretion in the HR- and LR-rats, but the degree of increase in the studied parameter is considerably greater in the experimental group of LR-rats.

2020 ◽  
Vol 73 (7) ◽  
pp. 1330-1333
Author(s):  
Ivanna I. Horban ◽  
Arsen A. Hudyma ◽  
Roman V. Maksymiv ◽  
Iryna V. Antonyshyn

The aim: to find out the effect of a two-hour tourniquets ischemia of the limb and acute blood loss on systemic disorders of the body in the postperfusion period. Materials and methods: The experiments were performed on 96 nonlinear male rats weighing 200-220 g. All experiments were performed under sodium thiopental anesthesia. In the first experimental group, two-hour tourniquets limb ischemia was simulated. In the second experimental group, acute blood loss was modeled. In the third experimental group, these lesions were combined. In 1 and 2 hours, as well as in 1, 7 and 14 days, the biliary function of the liver was determined in the experimental animals. Results: Two-hour tourniquets ischemia of the limb in the reperfusion period compared with the control was accompanied by a significant decrease in the rate of bile excretion, which reached a minimum value in 3 h – 1 day of the experiment and returned to the control level in 14 days. After the simulation of acute blood loss, the rate disturbance of bile excretion became significantly greater in all observation periods. The complication of acute ischemia-limb reperfusion caused a greater decrease in the rate of bile excretion with a maximum in 1 day of the experiment. Under these conditions, at 1, 7, and 14 days, the indicator was statistically significantly lower than in the other study groups. Conclusions: In the case of acute blood loss, complicated by two-hour tourniquets ischemia of the limb, the reperfusion period is accompanied by a summation of the negative impact of blood loss, ischemia and reperfusion of the limb on the functional state of the liver, which is a significant decrease in the rate of bile excretion with a maximum in 1 day, which further increases, but up to 14 days does not reach the level of control.


2021 ◽  
Vol 11 (1) ◽  
pp. 326-337
Author(s):  
D. O. Sikirynska ◽  
A. A. Hudyma ◽  
K. A. Pokhodun ◽  
I. V. Antonyshyn

Introduction. The development of multiorgan dysfunction and insufficiency is one of the serious complications of severe multiple and combined lesions. In their pathogenesis, a key role is played by secondary lesions of organs remote from the site of direct injury, which is caused by the systemic response of the body to inflammation and is a characteristic feature of traumatic disease. As a model of the development of organ damage in experimental polytrauma, the biliary function of liver is often investigated. However, the features of systemic disorders, in particular, the biliary function of liver, in conditions of severe skeletal injury, depending on the resistance to hypoxia, have not been studied enough.Purpose: to determine the dynamics of biliary function of liver in case of cranioskeletal trauma complicated with blood loss among rats with different resistance to hypoxia during the early period of traumatic disease and to evaluate the effectiveness of thiocetam in the correction of identified disorders.Materials and methods. 108 nonlinear white male rats weighing 180-200 g were used in the experiments. Previously, individual resistance to hypoxia was determined, rats were divided into two groups: with high- and low-resistance (HR and LR) animals to hypoxia. Subsequently, HR and LR rats were divided into 4 groups: one control and three experimental. Under conditions of thiopentale sodium anesthesia (40 mg kg-1) the first experimental group HR and LR of rats was had cranioskeletal trauma, the second - acute blood loss in the amount of 20-22% of circulating blood volume, the third experimental group after application of cranioskeletal injuries and acute blood loss in order to correct HR and LR-rats were thrown Thiocetam intraperitoneally, dose 250 mg kg-1 of body weight 1 time per day. Animals of the control and experimental groups in 1, 3 and 7 days after injury were catheterized the common bile duct, collected bile, in which the content of total bile acids was determined.It was found out that laboratory white rats, which are genetically different in resistance to hypoxia, also differ in the intensity of biliary function of liver. Among HR rats, the bile content of total bile acids was higher than that among LR rats. Under the influence of cranioskeletal injury, the bile content of total bile acids decreased among both HR and LR rats. Despite the lower initial content of total bile acids in the bile of LR rats, under the influence of cranioskeletal trauma in this group, the degree of the studied indicator reduction was significantly greater than among HR rats, indicating greater sensitivity of LR rats to pathogens of traumatic disease, which lead to damage to the microsomal monooxygenase system of hepatocytes. Under the conditions of acute blood loss additional modeling, the disorders were more visible, but the result was statistically significant only among LR rats in 3 days of the experiment. In addition, LR rats had a greater degree of reduction of the studied indicator in 3 and 7 days of the experiment. Under the influence of seven-day-usage of Thiocetam in the groups of LR and HR rats with cranioskeletal trauma, the violation of total bile acids content in the bile became significantly lower compared to animals without correction. A similar result was found under conditions of additional acute blood loss. Under these conditions, the degree of increase of total bile acids content in the bile was greater among LR rats than among HR rats, which indicates a higher efficiency of Thiocetam among LR rats.Conclusions: 1. The content of total bile acids in the bile among intact HR-rats is significantly higher than among LR-rats. Under the influence of cranioskeletal trauma, the content of total bile acids in the bile is reduced compared to the control, but the degree of reduction is significantly greater among LR rats after 7 days of the experiment. Complication of cranioskeletal injury with acute blood loss causes a significantly greater reduction in the bile content of total bile acids among LR rats compared with HR rats after 3 and 7 days of the experiment. The use of Thiocetam is accompanied by a decrease of liver biliary dysfunction, which is more visible among LR rats with acute blood loss.


2020 ◽  
Vol 10 (12) ◽  
pp. 394-405
Author(s):  
I. Strelbytska ◽  
A. Hudyma

Introduction. In the structure of injuries from gunshot wounds dominate the limb injuries that are often complicated by massive bleeding from the main vessels. The only means of rescue on the battlefield is a timely application of a tourniquet. This ensures complete exsanguination of the limb. The duration of exsanguination should not exceed 2 hours. It is proved that in conditions of acute blood loss complicated by ischemia-reperfusion of the limb, there are prerequisites for the development of dysfunction of internal organs, which in turn exacerbates dysmetabolic and functional disorders, stimulates endotoxicosis and may be complicated by multiple organ failure. However, the patterns of formation of the syndrome of endogenous intoxication in the conditions of ischemia-reperfusion of the limb, acute blood loss and their combinations have not been studied. There are no data on the effect of Carbacetam on these processes. It is known that Carbacetam has proven itself to reduce the manifestations of dysfunction of internal organs in the conditions of ischemic-reperfusion syndrome of the limb.The objective of research: To establish the dynamics of endogenous intoxication in the conditions of ischemia-reperfusion of the limb, acute blood loss and their combination. To evaluate the effectiveness of Carbacetam in the correction of identified abnormalities.Materials and methods. The experimental studies were conducted on 108 white nonlinear male rats weighing 200-220 g, which were housed in standard vivarium conditions. All animals were divided into five groups: control and four experimental. Under thiopental-sodium anesthesia in the first experimental group was simulated ischemia-reperfusion of the limb, in the second – acute blood loss, and in the third – these injuries were combined. In the fourth experimental group, animals with acute blood loss and ischemia-reperfusion of the limb were intraperitoneally administered Carbacetam at a dose of 5 mg per kilogram of animal weight. After 1 and 2 hours, as well as after 1, 7 and 14 days in the blood serum was determined the content of middle-mass molecules (MMM254, MMM280).The results and discussion. It was found that ischemia-reperfusion of the limb in comparison with the control group is accompanied by a significant increase of the MMM254 fraction in the blood serum content. From the first hour of the experiment with a maximum after 1 day and normalization of the index up to 14 days. The content in the blood serum of the MMM280 fraction became significantly higher, from the control only after 1 day with subsequent normalization in the following terms of the experiment. After simulation of acute blood loss, both studied fractions of MMM increased from 1 hour of the experiment, reached a maximum after 1 day and did not return to the control level after 14 days. For the first time it was found that two-hour ischemia-reperfusion of the limb significantly aggravates the course of acute blood loss, which revealed a significantly higher content in the serum of fractions MMM254 and MMM280 compared to other experimental groups in almost all periods of the experiment. Due to the use of Carbacetam, the content of both studied fractions of MMM in the serum compared with animals without correction was significantly reduced after 7 and 14 days of the experiment. Although the studied parameters did not return to the level of the Carbacetam control group, it can be considered a pathogenetically justified means of reducing the level of endotoxicosis in the conditions of ischemia-reperfusion of the limb and acute blood loss.Conclusions. Simulation of limb ischemia-reperfusion is accompanied by accumulation of MMM254-280 fractions with a maximum after 1 day of the experiment and normalization up to 14 days. Acute blood loss causes an increase in the serum content of fractions MMM254-280 from 1 hour of the experiment, which up to 14 days do not reach the level of control. The detected disorders are significantly exacerbated after a combination of acute blood loss and ischemia-reperfusion of the limb. The use of Carbacetam in comparison with animals without correction is accompanied by a significant decrease in the content of MMM254-280 fractions in the serum after 7 and 14 days of the experiment.


2021 ◽  
Vol 11 (1) ◽  
pp. 351-360
Author(s):  
I. Strelbytska ◽  
A. Hudyma

Introduction. In the structure of modern injuries in wartime and peacetime the share of gunshot wounds increased significantly. The timeliness of applying a tourniquet is one of the main methods of saving lives on the battlefield. The patterns of formation of enteral insufficiency syndrome in conditions of acute blood loss complicated by ischemia-reperfusion of the limb have not been studied enough. There are no data on the features of violations of the absorption function of the small intestine in these conditions and the effectiveness of correction with Carbacetam, which is able to reduce the manifestations of acute hemic hypoxia and ischemic-reperfusion syndrome.The objective of research: To establish the peculiarities of the absorption function of the small intestine in the pathogenesis of acute blood loss, ischemia-reperfusion of the limb and their combination. To evaluate the effectiveness of Carbacetam in the correction of identified abnormalities.Materials and methods. The experimental studies were conducted on 108 white nonlinear male rats weighing 200-220 g, which were housed in standard vivarium conditions. All animals were divided into five groups: control and four experimental. Under thiopental-sodium anesthesia in the first experimental group was simulated ischemia-reperfusion of the limb, in the second group – acute blood loss, and in the third group – these injuries were combined. In the fourth experimental group, animals with acute blood loss and ischemia-reperfusion of the limb were intraperitoneally administered Carbacetam at a dose of 5 mg per kilogram of animal weight. After 1 and 2 hours, as well as after 1, 7 and 14 days studied the absorption function of the intestines by D-xylose test.The results and discussion. Simulation of limb ischemia-reperfusion compared with the control group causes a decrease in the content of D-xylose in the urine after 1 day of the reperfusion period. Also, acute blood loss is accompanied by a significant decrease in this indicator after 1 day. Until the end of the experiment the rate increases, but up to 14 days does not reach the level of control. The combination of acute blood loss and ischemia-reperfusion of the limb causes a decrease in the content of D-xylose in the urine starting from 1 hour of the experiment, which reaches a minimum after 1 day and remains at the same level until 14 days. In these terms the rate was the lowest compared to other studied groups. The use of Carbacetam for corrective purposes in rats with acute blood loss complicated by ischemia-reperfusion of the limb, compared with animals without correction significantly reduces the detected abnormalities after 7 days and more after 14 days of use.Conclusions. Complications of acute blood loss by ischemia-reperfusion of the limb causes a significant decrease in the absorption function of the small intestine after 1 day of the experiment. The intensity of disorders was significantly higher compared to other experimental groups. The use of Сarbacetam for 7-14 days in the reperfusion period in animals with acute blood loss complicated by limb ischemia-reperfusion, compared with animals without correction, causes a significant increase in the absorption function of the small intestine. This indicates the protective effect of the drug under the conditions of simulated pathology.


Author(s):  
A. V. Krupin ◽  
I. A. Shperling ◽  
P. A. Romanov ◽  
M. I. Shperling

Relevance.High efficiency of hypertonic (hyperosmolar) solutions in acute blood loss is known. However, data on changes in the body, developing as a result of infusion of such drugs (including cooled) in the providing of care after acute blood loss is limited or absent. This fact complicates the development of tactics in their use, especially in emergency situations at low temperatures.Intention.To reveal features of functional and laboratory indicators In experiments on animals as a result of infusion of warm (+22 °С) or the cooled (–3 °С) hypertonic solution based on hydroxyethyl starch and sodium chloride (HyperHAES, further – HHES) at the acute blood loss of 50 % of blood volume (BV).Methodology.Animals (20 male sheep) with modeled blood loss were distributed into 2 experimental and 2 control groups of 5 animals each. Sheep in the 1st experimental group were placed in the heat chamber with temperature –7 °С for 15 min. Then they underwent the intravenous infusion of a cooled HHES at a dose of 4 ml/kg of weight through the jugular vein with a disposable syringe (volume 20 ml) evenly with a speed of 60 ml per minute. After that they were left in the heat chamber until the time of 1 hour in total. Individuals in the 2nd experimental group were injected with an equivalent volume of warm solution during the corresponding periods of the experiment at an external temperature of +22 °C. 1 hour after beginning of the infusion all animals were intravenously injected with colloidal solution based on hydroxyethyl starch (“Voluven”) at an external temperature of +22 °C. During 1 day the dynamics of rectal temperature, arterial pressure, heart rate and respiratory movements, osmolarity of blood plasma and content of osmotically active components, quantitative indicators of red blood were evaluated.Results.Animals at a temperature of +22 °C or at a temperature of –7 °C died in (82 ± 3) min and (70 ± 5) min (p < 0.05) respectively after the start of exfusion. Intravenous fluids (warm or cooled HHES) ensured the survival in 100 % of cases. As a result of blood loss, subsequent infusion of cooled HHES and following presence in the heat chamber, rectal temperature in sheep decreased by 4.9 °C (14.2%, p < 0.05) relative to the initial values. Two and 4 min after infusion of cooled or warm HHES systolic blood pressure increased by 24.9 % (p < 0.05) and 14.9 % (p < 0.05), respectively, and were restored to the normal level during the following 40 min. Infusion of “Voluven” contributed to the stabilization of blood pressure within 1 day after infusion of HHES. Blood loss led to increased heart rate by 2.1 times (p < 0.05), infusion of HHES slightly reduced the severity of tachycardia. Within 10 minutes after the introduction of cooled HHES, dynamics of heart rate was less stable. Infusion of warm or cooled HHES increased osmolarity of blood plasma by 9.5–9.9 % (p < 0.05), which was associated with an increase of sodium and glucose concentrations in blood. Infusion of “Voluven” reduced osmolarity of blood plasma, which became similar to initial values at the end of Day 1 after infusion of HHES. Blood loss, infusion of HHES and “Voluven” decreased quantitative indicators of red blood via removal of red blood cells from the bloodstream, as well as compensatory and post-transfusion hemodilution.Conclusion.The infusion of warm or cold hypertonic saline (HyperHAES) ensures the survival of experimental animals in post-hemorrhagic period. The positive effect of the drug is associated with compensatory haemodilution (including increased osmolarity of blood plasma), as well as with better functioning of the cardiovascular system. Specific cooled HHES effects include an earlier and pronounced rise in blood pressure. Considering changes in functional and laboratory parameters after infusion of warm or cooled HHES, a reliable system should be developed to remove casualties from emergency areas and to take earlier and complete diagnostic and treatment measures.


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.


2002 ◽  
Vol 1 (4) ◽  
pp. 13-22
Author(s):  
V. T. Dolgikh

In the course of experiments in 210 white mongrel male rats, endured 5-min clinical death from acute blood loss the mechanisms of energy, carbohydrate, lipid metabolism disturbance in postresuscitated brain tissue have been studied. It has been established that primary and secondary hypoxia, metabolic acidosis, excessive lipid peroxidation process activity, endotoxemia, neuron overload by Ca ions appeared to be the principle pathogenetic factors of the abovementioned disturbances. Pathogenetic block-scheme of early postresuscitation metabolic disturbances in brain was presented. The validity of this block-scheme principle theses was demonstrated by means of gutimin antihypoxanths (50 mg/kg) and sodium γ-hydroxybutyrate (300 mg/kg), ionolantioxidant (100 mg/kg), slow isoptin Ca-canals blocker (0,1 mg/kg) injected before clinical death.


Author(s):  
O.V. Semaka ◽  
R.V. Lutsenko ◽  
E.M. Vazhnichaya

Magnetite nanoparticles are one of the extensively investigated and implemented into medical practice. They are known as having significant therapeutic potential in providing rapid recovery of hematological parameters after acute blood loss. Since the pathogenesis of acute blood loss, except of anaemia, includes other components (hypoxia, hypovolemia, acidosis), it is important to know how magnetite nanoparticles affect the parameters of these processes. The aim of this study was to investigate the effect of magnetite nanoparticles on changes in hydrogen index (pH) and blood electrolytes induced by acute blood loss. Materials and methods. The experiment was performed on 47 white male rats. Blood loss (25% of circulating blood) was simulated by puncture of the heart under the ether anesthesia. The nanoparticles’ solution (5-8 nm) was administered intraperitoneally immediately after the blood loss in a dose of 6.75 mg Fe/kg in a volume of at least 1 ml. In 3, 24 and 72 hours, and in 5 day interval, the blood pH and content of HCO3–, Na+, K+ and Ca2+ were checked. The data obtained were processed using one-way variance analysis ANOVA (Statistica for Windows 8.0). Results and discussion. It is shown that magnetite nanoparticles elevated the pH level in 3 hours, reduced in 24 hours and did not affect it in 72 hours and 5 days as compared to the control pathology. The administration of magnetite nanoparticles after 3 hours, 24 hours and 5 days resulted in increase in Na+ content compared to that in blood loss. An increase in the content of K+ took place after 24 hours as compared to the control pathology. Magnetite nanoparticles contributed to the normalization of Ca2+ after 72 hours. The content of HCO3– in all terms of observations ranged within normal limits, except for that in blood loss with magnetite nanoparticles introduced after 24 hours caused the increase of HCO3–in 1.2 times compared to the control pathology. Conclusion. Magnetite nanoparticles, administered to manage the acute blood loss syndrome, are able to modify the acid-base balance and electrolyte content in the blood for 5 days of recovery period that largely depends on the ability of non-iron to accelerate erythropoiesis and thus to restrain other components in the pathogenesis.


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