RU2388063C2 - Method for simulation of pancreonecrosis in rats - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to experimental medicine, can be used for simulation of an acute destructive pancreatitis. There is offered a surgery-based method for simulation of pancreonecrosis in rats involving midline laparotomy in the length 3.0±0.1 cm. Stomach and duodenum together with pancreas is introduced in a created wound. Transillumination is used to visualise Wirsung's duct of pancreas. Visually aided double ligature with a suture No. 0 is delivered through duodenal mesentery involving a regional vessel and a proximal one-third of the gland duct at the duodenal wall. The ligature is delivered on the right lateral abdominal wall and fastened. The laparotomy wound is closed, and there is an accurate visualisation of Wirsung's duct. The method eliminates injury of kidneys, ureter and great vessels, reduces trauma of mesentery tissues; it allows applying new dosage forms for approbation.

EFFECT: higher probability of successful results of simulation of the given disease.

4 cl

Description

The invention relates to experimental medicine, namely to the experimental form of acute pancreatitis, and can be used to model acute destructive pancreatitis.

Acute pancreatitis is one of the most frequent nosological forms and makes up 3% of cases among urgent diseases of the abdominal organs. Despite the large number of different surgical and conservative methods of treatment, mortality in acute pancreatitis continues to remain high - 10-15%, reaching 30-40% in destructive forms.

High mortality dictates the need to develop new methods of treatment for this serious disease. Tests of new drugs are carried out on a large number of experimental animals with acute pancreatitis.

Modeling of acute destructive pancreatitis in rats, in our opinion, is the most justified, because these laboratory animals have a digestive system similar to humans, also feed on tissues of organic origin, do not require large expenses for the purchase and maintenance.

A known method of modeling acute destructive pancreatitis in rats, including the introduction of a bile salt into the common bile duct, characterized in that 0.3 ml of a buffer solution containing 0.3 g of Tris-hydroxymethyl-aminomethane and 0.6 g is injected into the common bile duct sodium deoxycholate in 100 ml with a pH of 8.8, with a flow rate of 0.07 ml per minute and regulate the area of pancreatic necrosis by applying ligatures above or below the place where the additional pancreatic duct enters the common bile duct, see RF patent No. 2236709.

A known method of modeling acute necrotic pancreatitis, including the destruction of rat pancreatic tissue by Triton X-100, characterized in that a dose of 0.2 ml of a complex consisting of a 1% aqueous solution of X-100 Triton and 10% is injected into the pancreas of an adult rat aqueous solution of the amino acid lysine, taken in equal volumes, receiving formed pancreatic necrosis within 24-72 hours, see RF patent No. 2286608.

The disadvantages of these methods are their pharmacological orientation, and this will not always give a positive result due to the different personality of each experimental rat, in addition, they are quite complicated, because it is necessary to strictly maintain the speed of the input streams.

A known method according to K. Heinkel (1953) and De D Carvalnho (1959), in which hemorrhagic pancreatitis was induced in rats by temporarily compressing the bile duct and introducing transduodenally through the papilla of the nipple under a minimum pressure of 0.6 ml of a 2% solution of sodium tauchlorate or 1 mg trypsin in 0.6 ml of physiological saline or in the same volume of 1 mg of enterokinase and olive oil.

Negative sides

The great complexity of the technique requires opening the lumen of the duodenum and cannulation of the large duodenal papilla. Infection of the abdominal cavity with the contents of the gastrointestinal tract. High incidence of gut suture failure. The duration of the operation. Requires an operating magnifier or an operating microscope, see Sinovets A.S., Levitsky A.P., Michurin V.F. Experimental acute pancreatitis (literature review). // Journal "Pathological physiology". - 1980. - No. 1 - p. 41-46.

The prototype is a method in which, under anesthesia, after an upper median laparotomy, a 0.25% novocaine solution with a total volume of 1.0 ml is injected into paranephron, inguinal tissue and small intestine mesentery. The duodenum (duodenum) with the part of the pancreas (pancreas) connected with it by the ductal system is brought into the wound. A microirrigator with a fishing line in the lumen (turnstile) is laid on the front surface of the contact between the pancreatic duct and the duodenum, the ends of which at the upper and lower edges of the contact of the organs through the punctures of the dorsal wall of the abdomen are brought out. The pancreas and duodenum are returned to their original position. Under visual control, the pancreatic duct system is closed by pulling the ends of the microirrigator. The abdominal cavity is irrigated with 0.25% solution of novocaine, drained. Control of hemostasis. The abdominal cavity is sutured in layers tightly. After 60 minutes, fishing line is removed from the lumen of the microirrigator, restoring the patency of the pancreatic duct system. Perforated microirrigator is used both for summing up and for withdrawing medicinal substances and solutions. If this is not necessary, then the latter can be removed along with the fishing line.

The method does not require expensive equipment and materials. The method is not accompanied by the opening of the lumen of the duodenum and cannulation of the large duodenal papilla.

The disadvantages are as follows.

Transillumination of the mesentery of the duodenum, i.e. difficulty in finding the Wirsung duct of the pancreas. The need to use a microirrigator for conducting the thread, which increases the invasiveness of the mesentery of the duodenum, sharply increases the risk of bleeding due to damage to blood vessels. Withdrawal of the microirrigator to the dorsal wall of the abdominal cavity increases the risk of damage to the retroperitoneal vessels and kidneys with the ureters, and also causes compression of the portal vein. There is no clamping of the marginal vessel of the duodenum, which allows us to talk about using only one mechanism for the formation of pancreatic necrosis, which reduces the percentage of successful results of reproducing the model of this disease.

Source

Lugovoi A.O., Zarinskaya S.A., Vladimirov V.G., Popova E.Yu., Bylova N.A. "Modeling of acute destructive pancreatitis in an experiment." Electronic scientific journal "Morphology", 2007, volume 1-2. www.morphology.dp.ua

An object of the invention is to increase the likelihood of successful results in reproducing a model of a given disease.

To solve this problem, a method for modeling pancreatic necrosis in rats is proposed, including surgical intervention, characterized in that the upper median laparotomy is 3.0 ± 0.1 cm long, then the stomach and duodenum are introduced into the resulting wound together with the pancreas and by transillumination visualize the Wirsung duct of the pancreas; then, under the control of vision, double ligature is performed using thread number “0” using a curved stitching surgical needle through the mesentery of the duodenum with capture of the marginal vessel and the proximal third of the duct of the gland at the intestinal wall; then the ligatures are removed on the right side wall of the abdominal cavity and tied, the laparotomy wound is sutured; there is a clear visualization of the virusong duct of the pancreas; excretion of the ligature on the side wall of the abdominal cavity eliminates damage to the kidneys, ureter and large vessels, reduces injury to the mesentery tissue the duration of the disease after surgery is 7 or more days, and this allows the use of new dosage forms for testing.

Thus, this method:

- allows to minimize operation time;

- allows you to get a high reliable result of operations with minimal death of experimental animals, i.e. high repeatability of positive results;

- provides technical simplicity and accessibility of operations;

- provides the possibility of a simulated disease for a long time with the possibility of drug intervention and testing of new dosage forms and drugs for treatment and study of their effect.

It should be noted that the proposed method corresponds to the main economic postulate: “cost-effectiveness” and significantly exceeds all other known methods in terms of this indicator.

Claims (4)

1. A method for modeling pancreatic necrosis in rats, including surgical intervention, characterized in that the upper median laparotomy is performed (3.0 ± 0.1) cm long, then the stomach and duodenum are introduced into the resulting wound together with the pancreas and visualized by transillumination pancreas wirsung duct; then, under the control of vision, double ligature is carried out with thread number "0" through the mesentery of the duodenum with the capture of the marginal vessel and the proximal third of the duct of the gland at the intestinal wall; then the ligatures are removed on the right side wall of the abdominal cavity and tied, the laparotomy wound is sutured. 2. The method according to claim 1, characterized in that there is a clear visualization of the virusong duct of the pancreas. 3. The method according to claim 1, characterized in that the removal of the ligature on the side wall of the abdominal cavity eliminates damage to the kidneys, ureter and large vessels, reduces injury to the mesenteric tissue. 4. The method according to claim 1, characterized in that the duration of the disease after surgery is 7 or more days, and this allows the use of new dosage forms for testing.