Influence of cranioskeltal trauma, complicated with blood loss, on the bile-forming function of liver during the early period of traumatic disease among rats with different resistance to hypoxia and its correction

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

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

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

ОСОБЛИВОСТІ АКТИВАЦІЇ ПРОЦЕСІВ ЛІПІДНОЇ ПЕРОКСИДАЦІЇ В РАННІЙ ПЕРІОД КРАНІОСКЕЛЕТНОЇ ТРАВМИ, УСКЛАДНЕНОЇ КРОВОВТРАТОЮ, У ЩУРІВ З РІЗНОЮ РЕЗИСТЕНТНІСТЮ ДО ГІПОКСІЇ

Introduction. Injury is one of the current problems. Its structure is dominated by a combined craniocerebral and skeletal trauma, which is accompanied by the highest mortality. One of the markers of traumatic disease is the intensification of lipid peroxidation in tissues and organs, which underlies the pathogenesis of multiorgan failure. Under these conditions, the patterns of lipid peroxidation processes in individuals with different resistance to oxygen deficiency remain virtually unexplored. The aim of the study – to determine the peculiarities of the activation of lipid peroxidation in the early period of cranioskeletal trauma complicated by blood loss in rats with different resistance to hypoxia. Research Methods. The experiments were performed on 148 nonlinear white male rats weighing 180–200 g, which were on the standard diet of the vivarium. Previously, individual resistance to hypoxia was determined in rats and two groups were identified: high- and low-resistance. In animals, cranioskeletal trauma was simulated and combined with acute blood loss. After 1, 3 and 7 days in the liver of animals resistant to hypoxia, the content of reagents for thiobarbituric acid was determined – a screening marker of lipid peroxidation intensification. Results and Discussion. In response to cranioskeletal trauma in experimental animals there is an activation of lipid peroxidation of cell membranes of hepatocytes. Under conditions of additional blood loss, there is a layering of the influence of pathogenic mechanisms of trauma and hypoxemia, in which there is an increase in the formation of reagents in the liver to thiobarbituric acid. In highly resistant animals to hypoxia, the degree of accumulation of reagents for thiobarbituric acid in the liver was significantly lower than in low-resistant animals at all times. The obtained results indicate that in highly resistant animals, despite the higher intensity of lipoperoxidation in the initial state, the reaction to trauma is accompanied by less activation of lipid peroxidation processes than in low-resistant animals. This suggests a lower probability of developing multiorgan failure in highly resistant animals, which is of great practical importance and requires further study. Conclusion. In response to cranioskeletal trauma and its combination with acute blood loss in the acute period and the period of early manifestations of traumatic disease compared with control, there is an increase in the intensity of lipid peroxidation in the liver of highly and low hypoxia-resistant animals.Вступление. Травматизм относится к актуальным проблемам современности. В его структуре доминирует соединенная черепно-мозговая и скелетная травма, сопровождающаяся самой большей летальностью. Одним из маркеров развития травматической болезни является интенсификация липидной пероксидации в тканях и органах, что лежит в основе патогенеза развития полиорганной недостаточности. В этих условиях практически не изученными остаются закономерности процессов липидной пероксидации у особей с разной резистентностью к недостатку кислорода. Цель исследования – выяснить особенности активации процессов липидной пероксидации в ранний период краниоскелетной травмы, осложненной кровопотерей, у крыс с разной резистентностью к гипоксии. Методы исследования. Эксперименты выполнены на 148 нелинейных белых крысах-самцах массой 180–200 г, которые находились на стандартном рационе вивария. Предварительно у животных определили индивидуальную устойчивость к гипоксии и выделили 2 группы: высоко- и низкостойких. У крыс моделировали краниоскелетную травму и сочетали ее с острой кровопотерей. Через 1, 3 и 7 суток в печени разностойких к гипоксии животных определяли содержание реагентов к тиобарбитуровой кислоте – скрининговому маркеру интенсификации липидной пероксидации. Результаты и обсуждение. В ответ на краниоскелетную травму у подопытных животных активировались процессы липидной пероксидации клеточных мембран гепатоцитов. В условиях дополнительной кровопотери происходило наслоение влияния патогенных механизмов травмы и гипоксемии, при которых отмечали усиление образования в печени реагентов к тиобарбитуровой кислоте. У высокостойких к гипоксии животных степень накопления реагентов к тиобарбитуровой кислоте в печени был существенно меньше, чем в низькостойких крыс, во все сроки наблюдения. Полученные результаты указывают на то, что у высокостойких животных, несмотря на высокую интенсивность липопероксидации в исходном состоянии, реакция на травму сопровождалась меньшей активизацией процессов липидной пероксидации, чем в низькостойких крыс. Это позволяет предположить более низкую вероятность развития полиорганной недостаточности в высокостойких животных, что имеет большое практическое значение и требует дальнейшего изучения. Вывод. В ответ на краниоскелетную травму и ее сочетание с острой кровопотерей в острый период и период ранних проявлений травматической болезни, по сравнению с контролем, отмечают рост интенсивности липидной пероксидации в печени высоко- и низкостойких к гипоксии животных, степень которой существенно больше в низкостойких крыс.Вступ. Травматизм належить до актуальних проблем сьогодення. У його структурі домінує поєднана черепно-мозкова та скелетна травма, яка супроводжується найбільшою летальністю. Одним з маркерів розвитку травматичної хвороби є інтенсифікація ліпідної пероксидації у тканинах та органах, що лежить в основі патогенезу розвитку поліорганної недостатності. За цих умов практично не вивченими залишаються закономірності процесів ліпідної пероксидації в особин з різною резистентністю до нестачі кисню. Мета дослідження – з’ясувати особливості активації процесів ліпідної пероксидації в ранній період краніоскелетної травми, ускладненої крововтратою, у щурів з різною резистентністю до гіпоксії. Методи дослідження. Експерименти виконано на 148 нелінійних білих щурах-самцях масою 180–200 г, які перебували на стандартному раціоні віварію. Попередньо у тварин визначили індивідуальну стійкість до гіпоксії та виділили 2 групи: високо- і низькостійких. У щурів моделювали краніоскелетну травму та поєднували її з гострою крововтратою. Через 1, 3 і 7 діб у печінці різностійких до гіпоксії тварин визначали вміст реагентів до тіобарбітурової кислоти – скринінгового маркера інтенсифікації ліпідної пероксидації. Результати й обговорення. У відповідь на краніоскелетну травму в піддослідних тварин активувалися процеси ліпідної пероксидації клітинних мембран гепатоцитів. За умов додаткової крововтрати відбувалося нашарування впливу патогенних механізмів травми і гіпоксемії, при яких відмічали посилення утворення в печінці реагентів до тіобарбітурової кислоти. У високостійких до гіпоксії тварин ступінь накопичення реагентів до тіобарбітурової кислоти в печінці був суттєво меншим, ніж у низькостійких щурів, у всі терміни спостереження. Отримані результати вказують на те, що у високостійких тварин, попри вищу інтенсивність ліпопероксидації у вихідному стані, реакція на травму супроводжувалася меншою активізацією процесів ліпідної пероксидації, ніж у низькостійких щурів. Це дозволяє припустити нижчу вірогідність розвитку поліорганної недостатності у високостійких тварин, що має вагоме практичне значення і вимагає подальшого вивчення. Висновок. У відповідь на краніоскелетну травму та її поєднання з гострою крововтратою в гострий період і період ранніх проявів травматичної хвороби, порівняно з контролем, відмічають зростання інтенсивності ліпідної пероксидації в печінці високо- і низькостійких до гіпоксії тварин, ступінь якої суттєво більший у низькостійких щурів