EA030904B1 - Method for therapy of ischaemic lesion of liver during its resection - Google Patents

Abstract

The invention relates to medicine, particularly experimental surgery, and may be applied to therapy, correction, and prevention of consequences of ischemic impact to the liver in condition of its temporary exclusion from blood circulation. Result of the invention consists in therapy, correction, and prevention of consequences of ischemic and reperfusion lesions in liver, which occur in condition of its temporary exclusion from blood circulation during resection, extension of safe exsanguination period for liver, and thus, avoiding gross bleeding during surgery on liver. For that, resection of liver is performed in experimental animal, comprising clamping hepatoduodenal ligament, and serotonin adipate is infused: during the surgery, into hepatoduodenal ligament before and immediately after its clamping, by 0.2 mg/kg body weight in 5.0 ml of mafusol infusion solution, in slow flow, and then after the surgery, on day 1 via catheter inserted into hepatoduodenal ligament in dose of 0.5 mg/kg body weight in 75.0 ml of mafusol infusion solution at rate 30 drops per minute at 16:00 and 20:00, and on day 2 and day 3, at 8:00, 12:00, 16:00 and 20:00, whereupon the catheter is removed from abdominal cavity at the end of day 3; on day 4 to day 9 serotonin adipate is infused daily, in slow flow, at 8:00 in dose of 0.4 mg/kg body weight in 5.0 ml of mafusol infusion solution; additionally, intravenous slow flow infusion is performed daily from day 1 to day 9: heptral as injection solution in dose of 10 mg/kg body weight at 10:00, mexicore as 5% solution in dose 10 mg/kg body weight at 14:00, and clarithromycin in 10.0 ml of mafusol infusion solution in dose 10 mg/kg body weight at 18:00.

Description

The invention relates to medicine, namely to experimental surgery, and can be used for the treatment, correction and prevention of the effects of ischemic effects on the liver in the conditions of its temporary shutdown from the circulation. The technical result of the invention is the treatment, correction and prevention of ischemic and reperfusion injuries of the liver that occur during organ resection under conditions of temporary shutdown from the circulation, prolonging safe periods of bleeding the liver and, as a result, preventing massive bleeding during operations on it. To do this, an experimental animal undergoes liver resection, including clamping of the hepatoduodenal ligament, serotonin adipinate is administered: during the operation, into the hepatoduodenal ligament before its compression and immediately after its release at 0.2 mg / kg of body weight into a 5.0 ml infusion solution mafusol jet slowly, then after surgery - on this day in the catheter placed in the hepatoduodenal ligament, at a dose of 0.5 mg / kg of weight per 75.0 ml of the infusion solution of mafusol at a rate of 30 drops per minute per 16 ⁰⁰ and 2 O ⁰⁰ , and on the second and third days - at 8 ⁰⁰ , 12 ⁰⁰ , 16 ⁰⁰ and 2 O ⁰⁰ , after which, at the end of the third day, the catheter is removed from the abdominal cavity, and from the fourth to the ninth day, serotonin adipinate is injected intravenously, intravenously, at a slow rate at 8 ⁰⁰ at a dose of 0.4 mg / kg of body weight per 5.0 ml of mafusol infusion solution, an additional slow intravenous injection is carried out once a day, starting from the day of surgery for nine days: Heptral in the form of injection solution at a dose of 10 mg / kg body weight per 1O ⁰⁰ mexicor as a 5% solution at 10 mg / kg body weight ⁰⁰ to 14, laritromitsina in 10.0 ml mafusola infusion solution in a dose of 10 mg / kg body weight ⁰⁰ to 18.

The invention relates to medicine, namely to experimental surgery, and can be used when performing resections of the liver.

During liver resections, the problem of intraoperative bleeding with massive blood loss is one of the most important (Ghantsev Sh.H. Intraoperative liver perfusion during surgical interventions on the abdominal organs. / / Soviet medicine. - 1987. - № 10 - c. 10-12). The most effective and optimal way to prevent this is the clamping of the hepatodvaginal duodenal ligament, which allows the surgeon to perform temporary hemostasis and conduct important stages of surgery with minimal blood loss (Verona GI Anatomical and physiological aspects of liver resection. - Novosibirsk: Nauka, 1983. - 185 p. ). But at the same time, portal hypertension, hypoxia and ischemia of the liver develop, hemodynamics destabilize, which, if the 20-minute threshold is exceeded, can lead to irreversible morphofunctional changes in the liver, including necrotic changes in hepatocytes (Antopolskaya EV. Correction of ischemic liver damage during its resection in conditions of bleeding: Auto-ref. ... Candidate of Medical Sciences - Kharkov, 1988. - 21 p.).

Various drugs with antioxidant action — dibunol, sodium oxybutyrate, cytochrome C, etc. — are used to prevent and correct disorders of metabolic processes in the cell. (Bilenko, MV Theoretical and experimental rationales for the use of antioxidant therapy for the prevention of acute ischemic organ damage. In k : Bioantioxidants in the regulation of normal metabolism and pathology. - M., 1982. - P. 195-213; Okovity S. Clinical pharmacology of antihypoxants (part II). // PHARM.index.-Pract. - 2004, 7 - P. 48 -63), but being their existing arsenal is limited and many well-known methods of application are not always able to prevent the occurrence and arrest the already developed ischemic lesion of the hepatic parenchyma.

Another direction in the fight against ischemia of the liver tissue is the desire to protect the microvasculature of the liver through the use of drugs with different mechanisms of action. In particular, attempts are being made to influence the development of microvascular smooth muscle failure (Simonenkov AP, Fedorov VD, Klyuzhev VM, Ardashev VN. Use of serotonin adipinate to restore impaired smooth muscle function in surgical and therapeutic patients .// Herald of Intensive Care - 2005 - № 1. - P. 1-6; Simonenkov A. P., Fedorov V. D. On the unity of tissue hypoxia and shock // Anest. And resuscitator. -2000 - № 6. - P. 73-76; Simonenkov A.P., Fedorov V.D., Fedorov A.V. and others. The mechanism of endogenous vasomotor and smoothness echnoy failure microvasculature .// Journal of Medical Sciences -. 1994. -№ 6. - S. 11-15). However, the methods used so far do not significantly increase the duration of liver anoxia.

The closest is a method of correcting ischemic liver damage in conditions of its bleeding, the essence of which is intravenous administration to an experimental animal in 5 mg G / o serotonin adipinate solution before and within 30 minutes after clamping the hepatic duodenal ligament to prevent the development of smooth muscle insufficiency of the microvasculature of the liver ( Patent No. 2134576 of March 11, 1998). This method helps to eliminate the smooth muscle insufficiency of the microvasculature, thereby improving endogenous vasomotorics.

The disadvantage of this method is that the authors confined themselves only to the use of a drug that regulates microcirculation without correcting other inevitably occurring disorders caused by ischemia, such as activation of lipid peroxidation processes and structural and functional changes of varying severity. (Bezugly VP Hypoxia and its role in liver pathology // Advances in Hepatology. - Riga, 1971. - Issue 3. - P. 94-110; Buyev AO Oxidative stress and its role in liver damage // Russian Journal of Gastroenterology, Hepatology, Coloproctology. - 2002. - Vol. XII. - No. 4. - P. 21-25; Merzhinsky VE, Konvay VD. Impact of the shutdown of regional blood flow in the liver on the state of lipid peroxidation / / Violation of regulation mechanisms in extreme and terminal states - Omsk, 1991. - P. 57-61), and double administration of serotonin adipinate only on the day of surgery weeks sufficient for the treatment and prevention of hypoxic and reperfusion injury of the liver tissue and its microvasculature, because the duration of medicinal effects has occurred and to take into account the possible morphological and biochemical changes in the liver.

The mechanisms of development of ischemic liver damage are complex. With the cessation of blood flow to the organ arise intrahepatic cholestasis, degenerative phenomena in organ increases cellular intoxication occur morphological changes in liver, developing smooth muscle insufficiency microvasculature liver, broken energosinteziruyuschaya function of the mitochondrial respiratory chain by limiting aerobic formation energy progressive oxygen deficiency accumulate active forms oxygen to form free radicals, endogenous reserves are depleted antioxidants and lipid peroxidation (LPO) processes with the accumulation of their products are activated, which ultimately leads to damage and destruction of organ cells (Bilenko, MV Ischemic and reperfusion organ damage (molecular mechanisms, prevention and treatment methods). - M .: Medicine, 1989. - 368 pp., Simonenkov AP, Fedorov VD Prevention and treatment of serotonin deficiency in surgical patients. / / Surgery.

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Journal them. N.I. Pirogov. - 2003. - № 3. - p. 76-80; Schnevajs VB, Levin G.S. The role of free radical oxidation in the pathogenesis of acute liver necrosis in visceral-ischemic shock. // Patol. physiology and experimentation. therapy, - 1996, - № 2.- p. 39-43; Yakovenko E.P., Grigoriev P.Ya., Agafonova N.A. et al. Intrahepatic cholestasis - from pathogenesis to treatment // Practicing physician. 1998. № 13 (2). - p. 20-24). It is obvious that under the influence of ischemia in the liver interrelated and interdependent processes occur. Therefore, simultaneous exposure to several key pathological processes is necessary. Given the above, we consider it relevant and promising to use complex methods of correction of liver ischemia.

The technical result of the invention is the treatment, correction and prevention of ischemic and reperfusion injuries of the liver that occur during organ resection under conditions of temporary shutdown from the blood circulation, prolonging safe periods of bleeding the liver, and as a result, preventing massive bleeding during operations on it.

The technical result is ensured by the fact that an experimental animal undergoes liver resection, including clamping of the hepatoduodenal ligament, and serotonin adipinate is administered: during the operation, into the hepatoduodenal ligament before clamping and immediately after its release at 0.2 mg / kg of body weight 5.0 ml of infusion solution of mafusol jet slowly, then after the operation - on this day in the catheter placed in the hepatoduodenal ligament, at a dose of 0.5 mg / kg of weight per 75.0 ml of the infusion solution of the muf sol at a rate of 30 drops per minute to 16 ⁰⁰ and 20 ^00, and the second and third day - 8, ^00, 12, ^00, 16 and 20, ^00, whereupon at the end of the third day the catheter from the peritoneal cavity was removed and the fourth to ninth day daily serotonin adipinate is administered intravenously in a stream of slowly at 8 ⁰⁰ at a dose of 0.4 mg / kg of body weight per 5.0 ml of the infusion solution of mafusol, in addition, an intravenous stream of slow infusion is administered once a day, starting from the day of surgery for nine days: Heptral in as a solution for injection at a dose of 10 mg / kg body weight per 10 ⁰⁰ , mexicore as 5% solution at a dose of 10 mg / kg body weight at 14 ⁰⁰ , clarithromycin in 10.0 ml of an infusion solution of mafusol at a dose of 10 mg / kg body weight at 18 ⁰⁰ .

The pharmacological action of serotonin adipinate is due to the fact that it contributes to the normalization of vascular smooth muscle function (endogenous vasomotorics), reduces local hypoxia of internal organs, improves metabolism in hypoxia zones. It is well absorbed and distributed in organs and tissues, remaining in the blood plasma for 8 hours (Russian Medicines Radar 2008 - M., Radar - 2008, 2007 - P. 800-801).

The pharmacological action of mexicor is predetermined by inhibition of lipid peroxidation, increased activity of the antioxidant system, activation of the energy-synthesizing functions of mitochondria, improvement of energy metabolism in the cell, ability to maintain the level of macroergs, including during hypoxia. Activates intracellular protein and nucleic acid synthesis, enzymatic processes of the Krebs cycle, promotes glucose utilization, synthesis and intracellular accumulation of ATP, restores membrane structure and functions, has a modulating effect on membrane-bound enzymes, ion channels, receptor complexes. The Mexicor improves the metabolism and blood supply of the internal organs, the rheological properties of the blood and the microcirculation, has anti-ischemic properties: improves blood flow, limits the zone of ischemic damage and stimulates reparative processes; increases the body's resistance to the effects of extreme factors and oxygen-dependent pathological conditions; promotes the regression of signs of vasomotor instability. The half-life of the drug varies between 8-12 hours (Register of Medicinal Products of Russia Radar Station 2008 - M., Radar Station - 2008, 2007 - P. 538-540).

The use of Heptral replenishes ademethionine deficiency and stimulates its production in the body, primarily in the liver and brain; it participates in the biological transmethylation reactions, provides the redox mechanism of cellular detoxification, increases the solubility of bile acids and their removal from the hepatocyte, protects the membranes of liver cells from toxic effects. Heptral acts as a stimulator of cell regeneration and proliferation of hepatocytes, normalizes metabolic reactions in the liver, has a choleretic effect due to increased mobility and polarization of hepatocyte membranes and contributes to the restoration of bile synthesis and current. As a result of exposure to Heptral, the functions of the liver are restored with an improvement in the metabolic processes and microsomal oxidation occurring in it, and the suppression of the formation of fibrous tissue. The wide spectrum of action of this drug is manifested by its hepatoprotective, choleretic, cholekinetic, neuroprotective, antioxidant, detoxifying, regenerating and antifibrotic properties. After iv administration of Heptral, the pharmacokinetic profile of ademetionine is biexpotential with a fast distribution phase in the tissues and clearance with T1 / 2 of about 1.5 hours; absorption with i / m administration is 96%, Cmax is reached 45 minutes after application; plasma concentrations decrease to baseline values within 24 hours (Vidal Handbook. Drugs in Russia. - M .: AstraPharmService, 2004. - C. B-350-B-351).

Clarithromycin, a 14-membered macrolide antibiotic, has a number of properties required for liver resections. It is characterized by pronounced antimicrobial activity, which is also of particular importance in conditions of exposure to ischemia, is active against many microorganisms.

- 2 030904 mov, incl. intracellular. Like all macrolides, clarithromycin has not only anti-inflammatory, but also immunomodulatory effects. After intravenous administration, clarithromycin is rapidly distributed to all tissues and body fluids and penetrates well into them, creating concentrations several times higher than plasma levels. When used in the dosage of T1 / 2 used by us, clarithromycin ranges from 5-7 h to 7-9 h (Register of Medicines of Russia Radar Station 2011 - M., 2010, - P. 412-419). The use of macrolide antibiotics, in particular clarithromycin, has a pronounced endothelio-and cardioprotective effect, helps to reduce the level of malondialdehyde, ketodienes, diene conjugates, which are markers of the intensity of POL in blood (Chernomortseva ES A.S. 2226101 RU C2, AK61 / 314870 The method of limiting the zone of necrosis in the simulation of coronary-occlusive myocardial infarction in animals with a reduced antioxidant background. Kursk State Medical University, No. 2002104522; Bull. 9 - 30 p.). They are distinguished by their ability to inhibit the initiation stage of free-radical reactions of POL, preventing a whole cascade of negative oxidative reactions leading to disruption of the integrity of cell membranes, which is associated with their own antioxidant properties of drugs (Chernomortsev, ES. Effect of macrolides on endothelium and myocardial functionalities in experimental modeling of 1-name-induced endothelial dysfunction // Kursk Scientific Practical Gazette Man and his health. - 2010, № 1.- p. 30-33).

Mafusol (Potassium chloride + Magnesium chloride + Sodium chloride + Sodium fumarate (Potassium chloride + Magnesium chloride + Sodium chloride + Sodium fumarate) - saline infusion solution, the main pharmacologically active component of which is sodium fumarate - antihypoxant, activates the adaptation of the cell to oxygen deficiency. Its the action is due to the participation in the reactions of reversible oxidation and reduction in the Krebs cycle. During these reactions, ATP is synthesized in an amount sufficient to maintain the functions of the body's cells during hypoxia. In metabolic acidosis p It has an alkalizing effect, its osmolarity is 400-410 mOsm / L, under hypovolemic conditions it quickly replenishes BCC, prevents tissue dehydration, reduces blood viscosity and improves its rheological properties, increases diuresis, promotes detoxification processes, reduces the concentration of intermediate and final products in blood lipid peroxidation (antioxidant properties) (Selivanov, EA, Slepneva, LV, Alekseeva, NN Fumarate-containing infusion solutions as a means of choice in the provision of emergency medical care. // Medicine of extreme situations. - M., 2012. - № 1 (39). - p. 85-94; Selivanov E.A., Slepneva L.V., Alekseeva N.N. et al. The efficacy of using fumarate-containing drugs of multifunctional action in the infusion therapy of emergency conditions. // Bulletin SPBGMA them. I.I. Mechnikov. - SPb., 2006. - № 2 (7). - p. 150-153; Sofronov G.A., Selivanov E.A., Hanevich M.D. and others. The use of antihypoxant infusion solutions in surgery. // Bulletin of the National Medical-Surgical Center. N.I. Pirogov. 2011. Vol. 6. No. 1, p. 87-91, ISSN 2072-8255).

Taking into account the pharmacological actions of mexicor, serotonin adipinate, Heptral, clarithromycin and mafusol, it is obvious that when used in combination, these drugs complement each other, simultaneously affecting the main links of pathological processes in liver ischemia, and administering serotonin adipinate with mafusol in a hepatopa; affects the state of the vascular bed not only of the hepatic zone, but also of other organs and systems of the abdominal cavity and prevents the development of postoperative n Cutting intestines.

The method is as follows.

After treatment of the surgical field with 1% chlorhexidine digluconate solution under intravenous hexenal anesthesia (0.03 g / kg), an experimental animal (rabbit) is subjected to a laparotomy, serotonin adipinate 0.2 mg / kg of body weight is introduced into a hepatopathic duodenal ligament by 5.0 mafusola jet slowly, clamp it with an elastic intestinal clamp for 30 minutes. Then perform resection of the left outer lobe of the liver. After the blockade of the hepatoduodenal ligament has been removed, serotonin adipate 0.2 mg / kg bodyweight 5.0 mafusol is introduced into it again slowly. Following this, a polyvinyl chloride catheter is inserted into the hepato-duodenal ligament, the abdominal cavity is dried, hemostasis is monitored, and the wound of the anterior abdominal wall is sutured in layers, and the catheter is fixed to the skin with a ligature. On the same day, the animal is given Heptral in the form of an injection solution administered at a dose of 10 mg / kg body weight per 10 ⁰⁰ , a Mexicor in the form of a 5% solution is administered at a dose of 10 mg / kg body weight at 14 ⁰⁰ , serotonin adipinate is fed into the catheter at a dose of 0, 5 mg / kg of weight per 75.0 mafusol at a rate of 30 drops per minute at 16 ⁰⁰ , clarithromycin is administered intravenously in a stream at 10.0 infusion solution of mafusol at a dose of 10 mg / kg of weight at 18 ⁰⁰ , and serotonin adipinate is fed into the catheter at a dose of 0 , 5 mg / kg of weight per 75.0 mafusol with a speed of 30 drops per minute at 20 ⁰⁰ ; On the second and third day, serotonin adipate is injected into the catheter at a dose of 0.5 mg / kg of weight by 75.0 mafusol at a rate of 30 drops per minute at 8 ⁰⁰ , 12 ⁰⁰ , 16 ⁰⁰ and 20 ⁰⁰ , at the end of the third day the catheter from the abdominal Cavities are removed and from the fourth to the ninth day every day serotonin adipate is administered intravenously in a slow-paced manner at 8:00 ^am at a dose of 0.4 mg / kg body weight 5.0 mafusol. During the period from the second to the ninth day, inclusive, intravenous infusion is slowly administered: Heptral in the form of injection solution is administered at a dose of 10 mg / kg body weight at 10 ⁰⁰ , mexicor in the form of a 5% solution is administered at a dose of 10 mg / kg body weight at 14 ⁰⁰ , clarithromycin 10.0 infusion solution of mafusol is administered at a dose of 10 mg / kg of weight at 18 ⁰⁰ .

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The study was performed on 24 rabbits of both sexes of the Chinchilla breed weighing from 2.5 to 3 kg. Experimental animals were observed up to 30 days, inclusive, they made blood sampling from the marginal ear vein for biochemical studies and liver biopsy to determine the content of lipid peroxidation products (POL) in the liver tissue homogenate. Determining the level of transaminase - activity of alanine aminotransferase (ALT) and aspartate aminotransferase (ACT) in blood serum - carried by Reitman-Frankel method, lactate dehydrogenase (LDH) - by SAVELYEV, bilirubin - at Endrashika method cholesterol by Ilkiv, β-lipoproteins by Burstein, urea - diacetyl-oxoxy method. In addition, the levels of alkaline phosphatase (alkaline phosphatase), total protein, prothrombin index (PTI), fibrinogen were determined by standard methods, and a thymol test was performed. Indicators of cytolysis syndrome were the activity of ALT, ACT and LDH. Indicators of cholestasis syndrome - alkaline phosphatase activity, the concentration of bilirubin, cholesterol and β-lipoproteins. Indicators of hepatodepressive syndrome were total protein concentration, fibrinogen content and prothrombin index; mesenchymal inflammatory syndrome - thymol test. The content of lipid peroxidation products - diene conjugates (DC) and malonic dialdehyde (MDA) - was determined by the method of I.D. Steel et al. (1977). Before starting the experiments, all animals collected blood from the marginal ear vein for biochemical studies (control). 15 animals throughout the study were administered Heptral, Mexican, Serotonin adipate and clarithromycin on mafusole according to our proposed scheme. The operative field was treated with a 1% chlorhexidine digluconate solution, under intravenous hexenal anesthesia (0.03 g / kg) an upper-middle laparotomy was performed and the hepato-duodenal ligament was clamped with an elastic intestinal clamp for 30 minutes. Then they tied the elements of the glisson and caval systems of the left external lobe of the liver. Following this, resection of the left external lobe of the liver was performed with its separation by a blunt and sharp path along the interlobar sulcus, application of liver seams to the stump of an organ of the organ and plastic surgery of the wound surface with a strand of the greater omentum on the pedicle. After removal of the clamp from the hepatoduodenal ligament, hemostasis was monitored, the catheter was placed in the hepato-venodenal ligament and the anterior abdominal wall wound was sutured in layers. Four rabbits were clamped by the hepatoduodenal ligament for 30 minutes and resection of the left external lobe of the liver without the administration of the studied drugs.

At 30-minute liver ischemia without pharmacological protection in the postoperative period, animals showed weakness, lethargy, lack of appetite, which indicated the severity of changes in the body of rabbits. One animal died on the 1st day after surgery, one animal died on the 2nd day, two rabbits survived up to 3 days.

The animals that were injected with a complex of drugs, consisting of Heptral, Mexicor, Serotonin Adipinate and Clarithromycin on mafusol, underwent surgery, the postoperative period was satisfactory, without complications, the survival rate of animals was 100%.

Morphological examination of the liver tissue after exposure to it with 30-minute ischemic anoxia without the use of Heptral, Mexicor, Serotonin Adipinate and Clarithromycin on the mafusole revealed that during the first two days of the experiment hemodynamic disorders increased, interstitial edema increased, the triad was given, and the route patterns were used by the triads. sections of the hepatic parenchyma with dystrophic and necrobiotic changes. In the triad zone and in the central zones of the hepatic lobes, widespread stasis was observed in the portal and central veins, the ruptures of their walls against the background of the increasing discomplexion of the lobes themselves. The hepatocyte cytoplasm was swollen, and isolated foci of plasmorrhagia were observed. Lipoidosis combined with granular and hydropic dystrophy with the predominance of the latter. By the 3rd day, dyscirculatory disorders increased in the liver tissue - dilatation and vascular plethora, cells with signs of coagulation necrosis were visualized, leukocyte infiltration was traced between the hepatic lobules and beams, and glycogen in the hepatocytes was practically absent.

A morphological study of the liver parenchyma in the group of animals using the studied drugs after 30 minutes of reperfusion revealed a weakly pronounced central venous congestion with isolated areas of granular dystrophy around them. Single round-cell infiltrates appeared in the triad zone, phagocytic particles were found in the cytoplasm of macrophages from the infiltrates, and in some cases even whole red blood cells, there were no necrotic changes in the hepatocytes. The glycogen content in the cytoplasm of hepatocytes on the first day after surgery decreased moderately, which was manifested by an insignificant decrease in the number of large granules of CHIC-positive substances. During the first three days, the expansion of the central veins stopped in the liver, the vacuolar dystrophy zones around them disappeared. By the 7th day of observation of vascular plethora, which until then had been insignificant, was no longer noted. The glycogen content in hepatocytes was quite high, the number of CHIC-positive substances increased rapidly. The 14th day after the operation was characterized by a further accumulation of glycosaminoglycans, at this stage the liver tissue actually returned to its original state and later practically did not differ from

- 4 030904 normal. Thus, although moderate morphological changes were observed in the liver parenchyma, the recovery period was rather short, there were pronounced positive changes throughout its course, characterized, in particular, by the significant preservation of glycogen granules in the cells and accelerated recovery of its reserves.

Without the combined use of Heptral, Mexicor, Serotonin Adipinate and Clarithromycin on mafusol, a simultaneous development of cytolytic, cholestatic and hepatodepressive syndromes was observed with 30-minute ischemic liver anoxia, as evidenced by the results of biochemical studies. After a 30-minute anoxia after half an hour of reperfusion, a significant increase in the digital values of transaminases was observed (Table 1; units of measurement: ALT, ACT and LDH mmol / (hl), DK and MDA - mmol / g; p <0.05; n = 24) and serum bilirubin (Table 2; units: bilirubin - μmol / l, alkaline phosphatase - mmol / (h · l), cholesterol - mmol / l, β-lipoproteins - g / l; p <0, 05; n = 24). In the same time interval, the content of alkaline phosphatase (Table 2) and urea increased, simultaneously accompanied by a decrease in the amount of fibrinogen, PTI and total protein (Table 3; unit of measure: fibrinogen - mg / l, PTI -%, total protein - g / l, urea - mmol / l; thymol test - unit; p <0.05; n = 24). The most significant changes in these indicators occurred on the 3rd day of observation. Compared with the control data, the increase in the ALT, ACT and LDH values on the third day was 4.39; 4.57 and 2.33 times, respectively, indicating the severity of cytolytic syndrome (Table 1). During the same period of time, the content of bilirubin increased 2.24 times (Table 2). The post-ischemic 3-day period was also characterized by an increase in alkaline phosphatase values by 1.26 times, β-lipoproteins by 1.22 times and a decrease in cholesterol concentration by 1.02 times as compared with the control (Table 2). These changes indicate the development of cholestasis syndrome. Hepatodepressive syndrome at the end of the third day of the postoperative period was manifested by a quantitative decrease in fibrinogen by 1.30 times, PTI by 1.31 times and total protein by 1.16 times compared with baseline data. By the third day, the urea content also sharply increased - by 1.43 times compared to the initial values (Table 3). The limiting values of the products of the FLOOR were recorded on day 3 with an increase in DK and MDA by 1.97 and 2.38 times, respectively, compared with the control (Table 1).

During the biochemical study of the blood serum of experimental animals that underwent ischemia correction with the proposed complex of drugs, after a 30-minute liver ischemia, after a 30-minute reperfusion, a slight increase in the cytolytic syndrome was observed: ALT 1.30 times, ACT 1.28 times, LDH in 1.01 times compared to the control. The peak of enzyme activity was registered on the 3rd day: ALT 1.76 times, ACT 2.22 times, LDH 1.34 times, after which there was a decrease in values. On the remaining observation periods, a significant decrease in transaminase activity was observed against the background of indicators in pharmacologically unprotected individuals: by the seventh day, a decrease in ALT activity was recorded 1.16 times, ACT 1.24 times, LDH 1.14 times with normalization of these indicators by 14 days (tab. 1).

___Table 1

experience conditions time after ischemia (day) ALT ACT LDH DK MDA 1. control - 0.74 ± 0.08 0.46 ± 0.06 1.37 ± 0.15 0.87 ± 0.081 0.072 ± 0.009 2. liver ischemia - 1.48 ± 0.12 1.15 ± 0.07 1.69 ± 0.19 1.29 ± 0.082 0.119 ± 0.006 3. liver ischemia; complex of drugs 0.94 ± 0.04 0.58 ± 0.07 1.37 ± 0.16 0.97 ± 0.083 0.086 ± 0.005 4. liver ischemia one 2.96 ± 0.15 1.73 ± 0.09 2.49 ± 0.11 1.63 ± 0.093 0.166 ± 0.009 5. liver ischemia; complex of drugs one 1.27 ± 0.11 0.69 ± 0.13 1.55 ± 0.09 1,09 ± 0,072 0.094 ± 0.007 6. liver ischemia 3 3.26 ± 0.26 2.12 ± 0.29 3.18 ± 0.21 1.72 ± 0.087 0.169 ± 0.011 7. liver ischemia; complex of drugs 3 1.29 ± 0.14 1.01 ± 0.06 1.81 ± 0.12 1.13 ± 0.089 0, Yu1 ± 0.009 8. liver ischemia; complex of drugs 7 1.10 ± 0.13 0.79 ± 0.08 1.59 ± 0.06 1.08 ± 0.084 0.087 ± 0.004 9. liver ischemia; complex of drugs 14 0.74 ± 0.05 0.45 ± 0.03 1.37 ± 0.07 0.88 ± 0.075 0.075 ± 0.006 10. liver ischemia; complex of drugs thirty 0.74 ± 0.04 0.46 ± 0.06 1.36 ± 0.08 0.85 ± 0.079 0.071 ± 0.009

Significant changes in cholesterol levels, β-lipoproteins, alkaline phosphatase and thymol samples were not observed during all periods of observation.

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table 2

experience conditions time after ischemia (day) ALT ACT LDH DK MDA 1. control - 0.74 ± 0.08 0.46 ± 0.06 1.37 ± 0.15 0.87 ± 0.081 0.072 ± 0.009 2. liver ischemia - 1.48 ± 0.12 1.15 ± 0.07 1.69 ± 0.19 1.29 ± 0.082 0.119 ± 0.006 3. liver ischemia; complex of drugs 0.94 ± 0.04 0.58 ± 0.07 1.37 ± 0.16 0.97 ± 0.083 0.086 ± 0.005 4. liver ischemia one 2.96 ± 0.15 1.73 ± 0.09 2.49 ± 0.11 1.63 ± 0.093 0.166 ± 0.009 5. liver ischemia; complex of drugs one 1.27 ± 0.11 0.69 ± 0.13 1.55 ± 0.09 1,09 ± 0,072 0.094 ± 0.007 6. liver ischemia 3 3.26 ± 0.26 2.12 ± 0.29 3.18 ± 0.21 1.72 ± 0.087 0.169 ± 0.011 7. liver ischemia; complex of drugs 3 1.29 ± 0.14 1.01 ± 0.06 1.81 ± 0.12 1.13 ± 0.089 0, youth, 009 8. liver ischemia; complex of drugs 7 1.10 ± 0.13 0.79 ± 0.08 1.59 ± 0.06 1.08 ± 0.084 0.087 ± 0.004 9. liver ischemia; complex of drugs 14 0.74 ± 0.05 0.45 ± 0.03 1.37 ± 0.07 0.88 ± 0.075 0.075 ± 0.006 10. liver ischemia; complex of drugs thirty 0.74 ± 0.04 0.46 ± 0.06 1.36 ± 0.08 0.85 ± 0.079 0.071 ± 0.009

The thirty-minute shutdown of the liver from the bloodstream was also accompanied by a slight decrease in PET, total protein and fibrinogen, an increase in the content of bilirubin and urea during the first three days after the operation, with full recovery by 14 days (Tables 2, 3).

Consequently, the combined effect of heptral, mexicor, serotonin adipinate and clarithromycin on the background of 30-minute liver ischemia contributed to a pronounced normalization of biochemical processes, as evidenced by the dynamics of cytolytic and complete relief of cholestatic and hepatodepressant syndromes.

Table 3

experience conditions time after ischemia (day) fibrinogen PTI total protein urea thymol try 1. control - 3.88 ± 0.18 81.7 ± 2.11 70.1 ± 1.12 3.82 ± 0.29 1.43 ± 0.07 2. liver ischemia - 3.12 ± 0.14 80.3 ± 1.97 68.4 ± 2.03 3.97 ± 0.25 1.38 ± 0.07 3. liver ischemia; complex of drugs - 3.75 ± 0.16 80.9 ± 1.98 69.7 ± 1.74 3.83 ± 0.28 1.39 ± 0.04 4. liver ischemia one 3.09 ± 0.15 62.7 ± 1.47 61.3 ± 1.08 4.89 ± 0.33 1.47 ± 0.03 5. liver ischemia; complex of drugs one 3.72 ± 0.13 80.3 ± 1.94 68.8 ± 1.85 3.86 ± 0.26 1.38 ± 0.08 6. liver ischemia 3 2.97 ± 0.23 62.5 ± 1.39 60.4 ± 1.12 5.47 ± 0.25 1.51 ± 0.04 7. liver ischemia; complex of drugs 3 3.62 ± 0.14 79.7 ± 1.73 66.9 ± 1.16 3.91 ± 0.24 1.43 ± 0.06 8. liver ischemia; complex of drugs 7 3.80 ± 0.13 81.2 ± 2.01 68.8 ± 2.09 3.86 ± 0.30 1.44 ± 0.03 9. liver ischemia; complex of drugs 14 3.86 ± 0.16 81.6 ± 2.09 69.7 ± 1.76 3.83 ± 0.19 1.43 ± 0.05 10. liver ischemia; complex of drugs thirty 3.86 ± 0.23 82.5 ± 2.13 70.2 ± 1.19 3.81 ± 0.22 1.42 ± 0.05

Studying changes in the level of accumulation of lipid peroxidation products in the liver tissue after its 30-minute ischemia against the background of complex administration of Heptral, Mexicor, Serotonin adipinate and clarithromycin for all periods of observation, we stated a lower content of DC and MDA compared to the data obtained under the same conditions, but without the use of drugs (Table 1). So, after 30 min, the reperfusion of DC and MDA did not significantly increase, at the same time, being, respectively, 1.34 and 1.36 times lower than similar values without pharmacological support. And on the third day, the gap in testimony had increased to 1.49 (DC) and 1.64 (MDA) times. The same period corresponds to the maximum numerical values of the studied POL products. A comparison with the control data revealed a positive effect of the proposed complex of drugs: compared to the control on the 3rd day, the content of DC increased only 1.32 times, MDA - 1.44 times. In the future, the considered indicators quickly returned to normal by 14 days.

The obtained results indicate that, against the background of the administration of the proposed complex of drugs during an ischemic effect on the liver for 30 minutes, the intensity of the POL processes was significantly slowed down, which prevented the development of ischemic changes in the organ, significantly reduced the risk of possible liver damage due to hypoxia and provided both preventive and and therapeutic effect.

Thus, under the influence of complex exposure to Heptral, Mexicor, Serotonin adipinate and clarithromycin on mafusole, almost all the studied parameters after the third day of observation in their changes had a pronounced positive trend, manifested in the achievement of baseline values by the 14th day of observation.

Examples of specific applications.

Example No. 1. Rabbit No. 2. Operation of July 22, 2014

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After treatment of the surgical field with a 1% chlorhexidine digluconate solution under intravenous hexenal anesthesia (0.03 g / kg), an upper-midline laparotomy was performed, a hepato-duodenal ligament was treated with 4.0 ml of a 0.25% novocaine solution, it was squeezed with an elastic intestinal clamp for 30 minutes Then the elements of the glisson and caval systems of the left external lobe of the liver were ligated with ligatures. Following this, resection of the left external lobe of the liver was performed, with a blunt and sharp separation of the liver along the interlobar sulcus, and imposition of hepatic sutures on the organ stump. After removing the clamp from the hepatoduodenal ligament, hemostasis was monitored and the anterior abdominal wall wound was sutured in layers tightly.

The results of biochemical studies:

08.23.2015 - before surgery: ALT - 0.78 mmol / (h-l); AST - 0.45 mmol / (hl); LDH - 1.42 mmol / (h-l); bilirubin - 13.61 µmol / l; Alkaline phosphatase - 2.37 mmol / (hl); cholesterol - 3.82 mmol / l; β-lipoproteins - 0.29 g / l; fibrinogen - 3.95 mg / l; PTI - 83.1%; total protein - 71.6 g / l; urea - 3.64 mmol / l; thymol test - 1.38 units; DK - 0.94 mmol / g; MDA - 0.068 mmol / g.

08.23.2015 - after 30 minutes of reperfusion: ALT - 1.58 mmol / (hl); ACT - 1.19 mmol / (hl); LDH - 1.83 mmol / (hl); bilirubin - 18.54 μmol / l; Alkaline phosphatase - 3.03 mmol / (h-l); cholesterol - 3.94 mmol / l; β lipoproteins - 0.52 g / l; fibrinogen - 3.7 mg / l; PTI - 79.3%; total protein - 57.9 g / l; urea - 4.12 mmol / l; thymol test - 1.41 units; DK - 1.38 mmol / g; MDA - 0.126 mmol / g.

August 24, 2015: ALT - 3.02 mmol / (h-l); AST - 1.79 mmol / (h-l); LDH - 2.56 mmol / (h-l); bilirubin 26.67 μmol / l; Alkaline phosphatase - 3.18 mmol / (h-l); cholesterol - 3.85 mmol / l; β-lipoproteins - 0.49 g / l; fibrinogen - 3.02 mg / l; PTI - 62.3%; total protein - 59.4 g / l; urea - 4.71 mmol / l; thymol test - 1.49 units; DK - 1.64 mmol / g; MDA - 0.172 mmol / g.

August 25, 2015: ALT - 3.41 mmol / (h-l); AST - 2.33 mmol / (h-l); LDH - 3.29 mmol / (h-l); bilirubin 30.76 μmol / l; Alkaline phosphatase - 3.27 mmol / (h-l); cholesterol - 3.71 mmol / l; β-lipoproteins - 0.45 g / l; fibrinogen - 2.82 mg / l; PTI - 61.4%; total protein - 59.6 g / l; urea - 5.58 mmol / l; thymol test - 1.53 units; DK - 2.7 mmol / g; MDA - 0.179 mmol / g.

By the end of the third day of observation, the animal died.

Example No. 2. Rabbit No. 8. On the day of surgery, 09/05/2015, after treating the surgical field with a 1% chlorhexidine digluconate solution under intravenous hexenal anesthesia (0.03 g / kg), the rabbit was subjected to a laparotomy, injected into the hepatodenal duodenal ligament. slowly serotonin adipate 0.2 mg / kg bodyweight 5.0 mafusol, pressed it with elastic intestinal clamp for 30 minutes Then, a resection of the left external lobe of the liver was performed. After the blockade of the hepatodvaginal duodenal ligament was removed, serotonin adipate 0.2 mg / kg 5.0 times of mafusol was slowly injected into it. Following this, a polyvinyl chloride catheter was placed in the hepatoduodenal ligament, the abdominal cavity was dried, hemostasis was monitored, and the anterior abdominal wall wound was removed in layers, and the catheter was fixed to the skin with a ligature. On the same day, the animal was injected Heptral in the form of a solution for injection was administered at a dose of 10 mg / kg body weight per 10 ⁰⁰ , a Mexicor in the form of a 5% solution was administered at a dose of 10 mg / kg body weight at 14 ⁰⁰ , serotonin adipinate was fed into the catheter at a dose of 0, 5 mg / kg of weight per 75.0 mafusol at a rate of 30 drops per minute at 16 ⁰⁰ , clarithromycin was administered intravenously in an intravenous stream at 10.0 of an infusion solution of mafusol at a dose of 10 mg / kg of weight at 18 ⁰⁰ , and serotonin adipinate into a catheter at a dose of 0 , 5 mg / kg of weight per 75.0 mafusol with a speed of 30 drops per minute at 20 ⁰⁰ ; On the second and third days, serotonin adipate was injected into the catheter at a dose of 0.5 mg / kg of body weight by 75.0 mafusol at a rate of 30 drops per minute at 8 ⁰⁰ , 12 ⁰⁰ , 16 ⁰⁰ and 20 ⁰⁰ , at the end of the third day a catheter from the abdominal the cavities were removed and, from the fourth to the ninth day, the serotonin adipate was administered intravenously, intravenously, at a slow rate of 8 ^00, at a dose of 0.4 mg / kg of body weight by 5.0 mafusol. During the period from the second to the ninth day, inclusive, they were injected intravenously in a slow-paced manner: Heptral in the form of a solution for injections was administered at a dose of 10 mg / kg of body weight at 10 ⁰⁰ , mexicor in the form of a 5% solution was administered at a dose of 10 mg / kg of body weight at 14 ⁰⁰ , clarithromycin administered on 10.0 mafusol infusion solution at a dose of 10 mg / kg body weight at 18 ⁰⁰ .

The results of biochemical studies:

09/05/2015 - before surgery: ALT - 0.76 mmol / (hl); AST - 0.48 mmol / (hl); LDH - 1.35 mmol / (h-l); bilirubin - 13.49 µmol / l; Alkaline phosphatase - 2.51 mmol / (hl); cholesterol - 3.93 mmol / l; β-lipoproteins - 0.32 g / l; fibrinogen - 3.84 mg / l; PTI - 81.6%; total protein - 70.2 g / l; urea - 3.83 mmol / l; thymol test - 1.41 units; DK - 0.89 mmol / g; MDA - 0.075 mmol / g.

09/05/2015 - after 30 minutes of reperfusion: ALT - 0.95 mmol / (hl); ACT - 0.61 mmol / (h-l); LDH - 1.38 mmol / (h-l); bilirubin - 13.66 μmol / l; Alkaline phosphatase - 2.59 mmol / (hl); cholesterol - 3.91 mmol / l; β lipoproteins - 0.33 g / l; fibrinogen - 3.79 mg / l; PTI - 81.1%; total protein - 69.8 g / l; urea - 3.77 mmol / l; thymol test - 1.39 units; DK - 0.95 mmol / g; MDA - 0.086 mmol / g.

09/06/2015: ALT - 1.29 mmol / (hl); AST - 0.67 mmol / (hl); LDH - 1.55 mmol / (hl); bilirubin 15.02 μmol / l; Alkaline phosphatase - 2.76 mmol / (h-l); cholesterol - 3.89 mmol / l; β-lipoproteins - 0.34 g / l; fibrinogen - 3.73 mg / l; PTI - 80.7%; total protein - 69.2 g / l; urea - 3.85 mmol / l; thymol test - 1.38 units; DK - 1.01 mmol / g; MDA - 0.094 mmol / g.

09/08/2015: ALT - 1.31 mmol / (h-l); AST - 0.94 mmol / (h-l); LDH - 1.78 mmol / (h-l); bilirubin

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15.09 µmol / L; Alkaline phosphatase - 2.81 mmol / (h-l); cholesterol - 3.83 mmol / l; β-lipoproteins - 0.35 g / l; fibrinogen - 3.64 mg / l; PTI - 80.1%; total protein - 67.3 g / l; urea - 3.89 mmol / l; thymol test - 1.41 units; DK - 1.13 mmol / g; MDA - 0.102 mmol / g.

September 12, 2015: ALT - 1.09 mmol / (hl); AST - 0.76 mmol / (h-l); LDH - 1.58 mmol / (h-l); bilirubin 13.54 μmol / l; Alkaline phosphatase - 2.49 mmol / (h-l); cholesterol - 3.86 mmol / l; β-lipoproteins - 0.31 g / l; fibrinogen - 3.73 mg / l; PTI - 81.3%; total protein - 68.8 g / l; urea - 3.85 mmol / l; thymol test - 1.43 units; DK - 1.5 mmol / g; MDA - 0.087 mmol / g.

09/19/2015: ALT - 0.78 mmol / (hl); AST - 0.46 mmol / (h-l); LDH - 1.41 mmol / (h-l); bilirubin 13.49 μmol / l; Alkaline phosphatase - 2.48 mmol / (hl); cholesterol - 3.89 mmol / l; β-lipoproteins - 0.32 g / l; fibrinogen - 3.81 mg / l; PTI - 81.5%; total protein - 70.6 g / l; urea - 3.84 mmol / l; thymol test - 1.43 units; DK - 0.86 mmol / g; MDA - 0.095 mmol / g.

10/07/2015: ALT - 0.75 mmol / (hl); AST - 0.44 mmol / (h-l); LDH - 1.36 mmol / (h-l); bilirubin 13.46 μmol / l; Alkaline phosphatase - 2.47 mmol / (hl); cholesterol - 3.94 mmol / l; β-lipoproteins - 0.30 g / l; fibrinogen - 3.85 mg / l; PTI - 81.9%; total protein - 71.3 g / l; urea - 3.82 mmol / l; thymol test - 1.42 units; DK - 0.87 mmol / g; MDA - 0.074 mmol / g.

The postoperative period was satisfactory.

Example No. 3. Rabbit No. 15. On the day of the surgery, 09/19/2015, after treating the surgical field with a 1% chlorhexidine digluconate solution under intravenous hexenal anesthesia (0.03 g / kg), a rabbit was laparotomy and a duodenal ulcer was injected into the hepatoduodenal ligament slowly serotonin adipate 0.2 mg / kg bodyweight 5.0 mafusol, pressed it with elastic intestinal clamp for 30 minutes Then, a resection of the left external lobe of the liver was performed. After the blockade of the hepatodvaginal duodenal ligament was removed, serotonin adipate 0.2 mg / kg 5.0 times of mafusol was slowly injected into it. Following this, a polyvinyl chloride catheter was placed in the hepatoduodenal ligament, the abdominal cavity was dried, hemostasis was monitored, and the anterior abdominal wall wound was removed in layers, and the catheter was fixed to the skin with a ligature. On the same day, the animal was injected Heptral in the form of a solution for injection was administered at a dose of 10 mg / kg body weight per 10 ⁰⁰ , a Mexicor in the form of a 5% solution was administered at a dose of 10 mg / kg body weight at 14 ⁰⁰ , serotonin adipinate was fed into the catheter at a dose of 0, 5 mg / kg of weight per 75.0 mafusol at a rate of 30 drops per minute at 16 ⁰⁰ , clarithromycin was administered intravenously in an intravenous stream at 10.0 of an infusion solution of mafusol at a dose of 10 mg / kg of weight at 18 ⁰⁰ , and serotonin adipinate into a catheter at a dose of 0 , 5 mg / kg of weight per 75.0 mafusol with a speed of 30 drops per minute at 20 ⁰⁰ ; On the second and third days, serotonin adipate was injected into the catheter at a dose of 0.5 mg / kg of body weight by 75.0 mafusol at a rate of 30 drops per minute at 8 ⁰⁰ , 12 ⁰⁰ , 16 ⁰⁰ and 20 ⁰⁰ , at the end of the third day a catheter from the abdominal the cavities were removed and, from the fourth to the ninth day, the serotonin adipate was administered intravenously, intravenously, at a slow rate of 8 ^00, at a dose of 0.4 mg / kg of body weight by 5.0 mafusol. During the period from the second to the ninth day, inclusive, they were injected intravenously in a slow-paced manner: Heptral in the form of a solution for injections was administered at a dose of 10 mg / kg of body weight at 10 ⁰⁰ , mexicor in the form of a 5% solution was administered at a dose of 10 mg / kg of body weight at 14 ⁰⁰ , clarithromycin administered on 10.0 mafusol infusion solution at a dose of 10 mg / kg body weight at 18 ⁰⁰ .

The results of biochemical studies

09/19/2015 - before surgery: ALT - 0.75 mmol / (h-l); AST - 0.44 mmol / (h-l); LDH - 1.36 mmol / (h-l); bilirubin - 13.38 µmol / l; Alkaline phosphatase - 2.47 mmol / (hl); cholesterol - 3.88 mmol / l; β-lipoproteins - 0.30 g / l; fibrinogen - 3.85 mg / l; PTI - 82.1%; total protein - 71.3 g / l; urea - 3.83 mmol / l; thymol test - 1.41 units; DK - 0.85 mmol / g; MDA - 0.071 mmol / g.

09/19/2015 - after 30 minutes of reperfusion: ALT - 0.94 mmol / (hl); ACT - 0.56 mmol / (hl); LDH - 1.33 mmol / (h-l); bilirubin - 13.72 µmol / l; Alkaline phosphatase - 2.64 mmol / (h-l); cholesterol - 3.90 mmol / l; β lipoproteins - 0.32 g / l; fibrinogen - 3.82 mg / l; PTI - 80.9%; total protein - 70.1 g / l; urea - 3.85 mmol / l; thymol test - 1.35 units; DK - 0.89 mmol / g; MDA - 0.091 mmol / g.

09.20.2015 g .: ALT - 1.27 mmol / (hl); AST - 0.68 mmol / (h-l); LDH - 1.56 mmol / (h-l); bilirubin 15.05 μmol / l; Alkaline phosphatase - 2.79 mmol / (h-l); cholesterol - 3.91 mmol / l; β-lipoproteins - 0.33 g / l; fibrinogen - 3.74 mg / l; PTI - 80.1%; total protein - 67.9 g / l; urea - 3.87 mmol / l; thymol test - 1.34 units; DK - 1.5 mmol / g; MDA - 0.096 mmol / g.

09/22/2015: ALT - 1.29 mmol / (hl); AST - 1.03 mmol / (h-l); LDH - 1.81 mmol / (h-l); bilirubin 15.10 µmol / l; Alkaline phosphatase - 2.83 mmol / (hl); cholesterol - 3.82 mmol / l; β-lipoproteins - 0.35 g / l; fibrinogen - 3.63 mg / l; PTI - 80.3%; total protein - 65.8 g / l; urea - 3.90 mmol / l; thymol test - 1.39 units; DK - 1.14 mmol / g; MDA - 0.105 mmol / g.

09/26/2015: ALT - 1.10 mmol / (hl); AST - 0.81 mmol / (h-l); LDH - 1.63 mmol / (h-l); bilirubin 13.59 μmol / l; Alkaline phosphatase - 2.52 mmol / (hl); cholesterol - 3.84 mmol / l; β-lipoproteins - 0.32 g / l; fibrinogen - 3.76 mg / l; PTI - 80.9%; total protein - 67.5 g / l; urea - 3.87 mmol / l; thymol test - 1.42 units; DK - 1.7 mmol / g; MDA - 0.086 mmol / g.

10/05/2015: ALT - 0.75 mmol / (hl); AST - 0.45 mmol / (hl); LDH - 1.38 mmol / (h-l); bilirubin 13.45 μmol / l; Alkaline phosphatase - 2.47 mmol / (hl); cholesterol - 3.90 mmol / l; β-lipoproteins - 0.33 g / l; fibrino

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10.21.2015 g .: ALT - 0.74 mmol / (hl); AST - 0.42 mmol / (h-l); LDH - 1.34 mmol / (h-l); bilirubin 13.39 µmol / l; Alkaline phosphatase - 2.44 mmol / (hl); cholesterol - 3.89 mmol / l; β-lipoproteins - 0.33 g / l; fibrinogen - 3.86 mg / l; PTI - 81.7%; total protein - 70.2 g / l; urea - 3.79 mmol / l; thymol test - 1.44 units; DK - 0.86 mmol / g; MDA - 0.075 mmol / g.

The postoperative period was satisfactory. The results suggest that the use of the proposed method for the prevention and treatment of the effects of ischemic effects on the liver with complex intravenous administration of Heptral, Mexicor, Serotonin adipinate and clarithromycin on mafusole according to our proposed scheme for 30 minutes of liver ischemia reduced the intensity and contributed to the normalization of biochemical processes , prevented the violation of the structure of the hepatic parenchyma, the development of cytolytic, cholestatic and hepatodepressive syndromes and associated pronounced functional morphological changes, thereby preventing the development of ischemic changes in the organ, which significantly reduced the severity of possible liver damage due to oxygen starvation and provided not only a protective, but also a therapeutic effect.

Thus, the proposed method allows us to extend the safe terms of bleeding the liver up to 30 minutes, provides treatment, correction and prevention of ischemic and reperfusion injuries of the liver tissue and its microcirculatory bed that occur during resection of this organ in temporary shutdown conditions from the blood circulation, helps prevent massive bleeding during liver surgery.

Claims (1)

CLAIM A method of treating ischemic liver damage during its resection, including clamping the hepatoduodenal ligament, administering serotonin adipinate: during the operation, into the hepatodenal duodenal ligament before clamping and immediately after its release at 0.2 mg / kg of body weight into 5.0 ml of infusion solution mafusol jet slowly, then after surgery - on this day in the catheter placed in the hepatoduodenal ligament, at a dose of 0.5 mg / kg of weight per 75.0 ml of the infusion solution of mafusol at a rate of 30 drops per minute at 16 ⁰⁰ and 20 ⁰⁰ , and on the second e and third day - ⁰⁰ 8, 12 ^00, 16 ⁰⁰ and 20 ^00, then at the end of the third day the catheter was removed from the abdominal cavity and the fourth to ninth day daily serotonin adipate slowly administered intravenously in a dose of ⁰⁰ 8 0.4 mg / kg weight per 5.0 ml of mafusol infusion solution, additionally carry out slow intravenous injection once a day, starting from the day of surgery for nine days: Heptral in the form of injection solution at a dose of 10 mg / kg of weight at 10 ⁰⁰ , mexicor as a 5% solution at 10 mg / kg 14 ⁰⁰ clarithromycin 10.0 mafusola liter infusion solution at a dose of 10 mg / kg body weight ⁰⁰ to 18.