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.

PECULIARITIES OF BILIARY FUNCTION OF THE LIVER IN THE DYNAMICS OF POLYTRAUMA IN THE EXPERIMENT

Relevance. Severe trauma is accompanied by the development of multiple organ dysfunction and the insufficiency of internal organs. The dynamics of changes in the functional state of the liver didn't investigate fully. It is the central organ of detoxification of the body, whose activity occurs in close integration with other organs and systems of the body. The objective is to find out the features of the biliary function of the liver in the dynamics of the developed model of polytrauma. Materials and methods. Polytrauma was performed using 62 nonlinear white male rats weighing 180-200 g under conditions of thiopental-sodium anesthesia (40 mg 1kg-1 intraperitoneally). In surviving animals, the biliary function of the liver was studied in 2 h, 1, 3, 7, 14, 21, and 28 days after injury. For this purpose, the common bile duct was catheterized, and bile was collected for 1 hour in animals under thiopental-sodium anesthesia (60 mg kg-1). The rate of bile excretion and the concentration of total bile acids, cholesterol, direct and indirect bilirubin in the selected portion of bile were determined. Based on these data, the rate of excretion of the studied components of bile was calculated. Euthanasia of rats throughout the experiment was performed by total bloodletting from the heart after previous thiopental-sodium anesthesia (60 mg kg-1 intraperitoneally). The obtained digital data were subject to statistical analysis. Results. In the conditions of experimental polytrauma, there is a violation of the biliary function of the liver. It is manifested in the period of an acute reaction to the trauma first (after 2 hours) by a significant it decreases, then (up to 1 day) development of polycholia - 1.52 times increased of bile secretion. Also increased excretion of the main components of bile, with their subsequent decrease to 7 days, development of the period of temporary improvement in 14 days with the repeated of exacerbation period in 21 days and approach to the norm - in 28 days. The decrease in bile secretion corresponds to a period of shock, which is characterized by the centralization of blood circulation and reduced blood supply to the organs of the gastrointestinal tract. Increased bile secretion and excretion of main bile components in 1 day after a severe injury is associated with the increased biliary polarity of hepatocytes and unloading of the liver from endotoxins. It accumulates due to tissue damage, microcirculation, and hypoxia. Subsequently, the indicators of the biliary function of the liver changed by the identified patterns of lipoperoxidation deviations, antioxidant protection, cytolysis, and endogenous intoxication. The pathogenesis of biliary disorders is the damage of the endoplasmic reticulum membranes, where the synthesis of the main components of bile. As well as the development of edema of the organ, which prevents the outflow of bile. Conclusion. The dynamics of the development of functional liver failure due to polytrauma coincides with the general pattern characteristic of the dynamics of other biochemical markers of traumatic disease. Namely: after 3 days of the post-traumatic period, there was a phase of maximum deepening of deviations of the studied indexes. After 7-14 days there was noted a phase of temporary improvement which is characterized by a change of indexes towards the norm. After 21 days there was a re-exacerbation of the pathological process. After 28 days the indexes changed towards the norm, but for most cases do not reach it. This means that in a critical state of the body the organs and systems coupling is getting worse, which are remote from the site of injury. It can be considered as a factor of compensation and adaptation directed to the survival of the organism.