Method for surgical treatment of traumatic splenic lesions with hyaluronic acid-based film

FIELD: medicine, surgery.

SUBSTANCE: one should apply a hemostatic film onto damaged spleen, moreover, as hemostatic material one should apply hyaluronic acid-based film (HA) being chemically associated with 5-aminosalicylic acid and impregnated with ferrum of the following total structural formula:

. Moreover, substitution degree of carboxylic groups with 5-aminosalicylic acid corresponds to 30-50% M. The innovation provides stimulation of fibroblastic activity and accelerated formation of granulations.

EFFECT: higher efficiency of therapy.

8 dwg

 

The present invention relates to medicine, in particular to surgery, and can be used in surgical treatment of patients with traumatic injuries of the spleen.

Despite the many proposed methods of suturing on the spleen during her traumatic injuries, none of them has proved its worth in connection with the eruption of the seams. Often, splenorrhaphy leads to an even more massive bleeding. A special problem remains extensive decapsulate spleen, which often occurs when it is iatrogenic damage. Thus hemostasis in large decapsulated surface to carry out hard enough.

The analogue of the present invention is a method of hemostasis at a superficial injuries of the spleen (II and III degree O.I.S.) dvuhkomnitny biological glue on the basis of fibrin (Tissucol; Measurement, Vienna, Austria), which turns fibrinogen mimic the final phase of the blood clot formation. Together with fibrin collagen is used substance for closing the open surface (Uranüs S., Mischinger H.-J., J. Pfeifer, L. Kronberger, Rabl h, Werkgartner G., Steindorfer p, Kraft-Kirz J. Hemostatic Methods for the Management of Spleen and Liver Injuries World J Surg. 1996 Oct; 20(8):1107-1115). The drawback of this method can be considered as the need to create a dry surface to solidify the adhesive, which can be achieved by vascular compression of the knife and the body within a few minutes. The disadvantages of the use of adhesive composites can be attributed to pronounced inflammatory response, unreliable in patients with severe bleeding and their use only as a supplementary means of hemostasis (Nazarenko, M. Efficacy of CO2laser and plasma scalpel injuries of the liver and spleen. //Proceedings of the VI international Congress of surgeons-hepatologists of CIS ″Topical issues of surgical Hepatology″. - Kiev: Annals of surgical Hepatology. - 1998. - Vol. 3, No. 3. - S-198).

The prototype of the present invention is the use for hemostasis spleen applications wounds drug ″efficiency″ (Nazyrov financial year with a co-author. Hemostasis of the wound surface when the injury of the liver and spleen.//Proceedings of the VI international Congress of surgeons-hepatologists of CIS ″Topical issues of surgical Hepatology″. - Kiev: Annals of surgical Hepatology. - 1998. - Vol. 3, No. 3. - C-199). The disadvantages of this method are that the hemostatic effect occurs in 5-10 minutes, not a high ability to stop bleeding with continued bleeding. In some cases not excluded exclusion hemostatic material with the development of intra-abdominal abscesses. In addition, the drug ″efficiency″ firm Nycomed has high value.

Technical rez is lthat of the present invention is improving the reliability of hemostasis, prevention of postoperative complications.

This technical result is achieved by the fact that at the time of surgical treatment regarding open or closed abdominal trauma with damage to the spleen, after inspection of the abdominal cavity, the elimination of hemoperitoneum and conditions for performing this operation on the damaged surface impose a film based on hyaluronic acid, a chemically related to 5-aminosalicylic acid and impregnated with iron, which when hit on her blood was softened and took the form of the body, tightly his obliga. This method is effective for ongoing bleeding low intensity. Additional fixing film is not required. After that make sanitation of the abdominal cavity and the mandatory control the drainage of the abdominal cavity in the region of the spleen. Re-examined the spleen and the left subphrenic space on the subject of bleeding. Through the use of the proposed method of hemostasis, it is possible to preserve the spleen. The ineffectiveness of this method was used by other methods or splenectomy.

For the production of hemostatic film using hyaluronic acid with the addition of iron. Hyaluronic acid (ha) is one of the main components of connective tissue, ladyship pronounced reparative action. Know the application of this film without impregnation with iron in surgery adhesive disease of the peritoneum for the prevention of adhesions. Hyaluronic acid (ha) is one of the main components of connective tissue, which has expressed a reparative action. An important property of hyaluronic acid is the absence of antigenic activity. Features chemically modified GC obtained from GC and 5-aminosalicylic acid (5-ASA) method, carbodiimide activation of the carboxyl groups of the polysaccharide. Ledger for the experiment was obtained on the basis of the Institute of Chemistry, Bashkir branch of the Russian Academy of Sciences. A modified GA with different degree of substitution of carboxyl groups (from 30% to 50% mole.) received the following way. Like all salicylates, modified GC capable of forming colored complexes with FeCl3that are poorly soluble in water connections. Worked the surface of the films of the modified GC solution of FeCl3and got water-insoluble materials.

Figure 1 shows the chemical formula of obtaining the modified hyaluronic acid.

Figure 2 demonstrated pattern of hemorrhage under the capsule at the edge of the wounds of the spleen through 1 day after the experiment. Paint hematoxylin-eosin. Microphoto, 10, Ob.

Figure 3 - ran the spleen and film through 1 day after the experiment. Paint hematoxylin-eosin. Microphoto, 10, Ob.

Figure 4 - hemostasis injury to the spleen through 1 day after the experiment. Paint hematoxylin-eosin. Microphoto, 10, Ob.

Figure 5 shows a destructive altered cells on the surface of the wounds of the spleen 3 days after the experiment. Paint hematoxylin-eosin. Microphoto, 10, Ob.

Figure 6 shows the proliferation of fibroblasts from the trabeculae in 3 days after the experiment. Paint hematoxylin-eosin. Microphoto, 10, Ob.

7 demonstrated formed delicate connective tissue capsule in the damaged area of the spleen 7 days after the experiment. Paint hematoxylin-eosin. Microphoto, 10, Ob.

On Fig shown granules of iron in the macrophages of the spleen in the immediate vicinity of the injury of the spleen 4 days after the experiment. The Reaction Of Perls. Microphoto, 10, Ob.

The indications for this method are extensive surface rupture of the capsule and superficial damage to the parenchyma of the organ. Contraindications to this method are damage to the spleen, located in the gate body, deep breaks with heavy bleeding, ruptured spleen, profuse bleeding.

Previously conducted an experimental study of 15 adult white rats. Under efern the m anesthesia produced verhnesadovoe laparotomy, the spleen was taken to the wound and made a resection of approximately 1/3 of the spleen in its lower part, and the cut direction was transverse to clinico spleen. Then decapsulated part imposes the appropriate size of the film that completely covers the damaged area with capture capsules. Assesses the condition of the fixed film. The latter was softened and densely adjoined to the affected area parenchyma due to its hygroscopicity. Bleeding through the film was not observed in any case. The wound was stitched. Animals were taken from experiment 1, 3 and 7 day after the experiment. Rats were scored, made a visual assessment of the damage zone, biopsy specimens for histological study.

A day after the conducted experiment visually on the wound surface was determined by the attached plate. On the border is attached to the capsule plate and intact capsule was determined clots, moderate swelling. In histological preparations all the damaged surface of the spleen and adjacent to the damaged zone, the spleen was filled shaped blood cells, especially erythrocytes, leukocytes (figure 2). Blood cells filled the narrow strip between the spleen and the plate (figure 3). The wound passed through the white and red purposelessly, and was traumatized trabeculae, as well as various blood vessels. Existing vessels (arteries of different caliber, arterioles, capillaries, venous sinuses) were in spasams state, i.e. hemostasis was achieved. As a result of injury of the spleen was noted secretion of inflammatory mediators, which was accompanied by enhanced exudation of the liquid portion of blood with subsequent tissue edema, leukocyte migration. When monocytes were attached to the endothelial cells of blood vessels. After attaching and rasplastyvanija leukocytes migrated through intercellular gaps in the perivascular area. The result of tissue damage and excretion of inflammatory mediators produced hemotoksicheskie factors, mainly protein-glycosaminoglycans complexes, whereas one component of this complex is hyaluronic acid attached to the wound surface of the spleen, and contributes to the acceleration of hemostatic processes. The wound surface was uneven configuration (figure 4). At the edge of the damaged parts singly or in groups met lymphocytes and erythrocytes, some of them were subjected to destructive processes.

After 3 days of the experiment, the wound surface was smoother surface. A large part of the freely located lymphoid cells were subjected to destructive p is acessem, especially often mentioned karyopyknosis and karyorhexis cells. Degenerative changes showed some cellular elements of the spleen, located in the immediate vicinity of the line of damage, they diffuse and intensively stained (figure 5). Near degenerating cells were located as lymphocytes, and erythrocytes. In the damage zone of the splenic blood vessels of moderate blood, sinuses filled with leukocytes and erythrocytes, however, perivascular edema persisted. At some distance from the damaged area red and white pulp without severe pathology. It was noted some of venous stasis, whereas arterial blood vessels intact.

At the edge of the damaged connective tissue sheath thickened by increasing the number of fibroblasts They are closely associated with connective tissue formations of the trabeculae of the spleen (6). Therefore, the wound surface of the spleen began to cover delicate scar tissue due to proliferating and synthetically active fibroblasts, which ensured the effectiveness of wound healing. Migration of fibroblasts began with the edges of the wound, however, their movement into the wound is not a continuous layer, and by ″crawling″ cells with different intensity. Cell migration in wound surface accompanied the axis gradual synthesis of very thin fibrillar fibers. As mentioned, with the development of fibroblastic cells from the remaining edges of the connective tissue sheath, the formation of connective tissue structures and realized by fibroblasts numerous trabeculae. This fusiform or mnogochastichnye fibroblasts of the connective tissue septa pulled to the surface area and gradually sprawled on the wound surface. First they had a single location. Fibroblasts closely adjoined to the lymphocytes of the red and white pulp. The wound defect spleen were closed mainly due to the concentric contraction of wound edges, however the size of the regenerate gradually decreased by the displacement of fibroblasts and connective tissue septa of the body. Thus, wound closure was due to two interrelated sources: the development of the connective tissue capsule of the wound edges and the migration and proliferation of fibroblasts of the connective tissue trabeculae body. Cells are moved towards each other and gradually formed a continuous thin connective capsule. However, still remained small areas of wound surface, devoid of fibroblast sheath.

On the 7th day after the experiment in the vast majority of injured surface of the spleen was even, in some months the Ah surface had a very winding course (Fig.7). The wound was completely closed tender connective tissue structure. While the fibroblasts had two - or three-layer arrangement. Young fibroblasts began to synthesize the characteristic components of the intercellular substance of the connective tissue (glycosaminoglycans and collagen fibers). In the synthesis of extracellular matrix of loose connective tissue with active participation of Mature fibroblasts. Collagen fibers are very thin, had a bed is weakly meandering course on the background of the basic substance formed of loose connective tissue. Along with proliferative processes mentioned the death of some fibroblasts mechanism of apoptosis with parallel collagenolytic activity other fibroblasts and macrophages regenerate. In most cases, there is a weakening signs of developing vascular dystonia in the area caused mechanical injury of the spleen. Blood vessels stroma and parenchyma of the spleen were no significant changes in the venous sinusoids of the temperate blood, red and white pulp of the spleen without visible changes in the immediate vicinity of superimposed plates of hyaluronic acid, and in remote areas from the trauma of the body.

To determine the functional status in the damaged area of the spleen was performed assessment of the degree of elimination of old and damaged red blood cells, as well as toxic effects on immunocompetent cell reaction Perls to determine iron in macrophages. Histochemical reaction for iron was determined only in the red pulp, white pulp activity was determined only in the marginal zone, where it was noted moderate reaction for iron. The splenic cords and venous sinusoids of the red pulp of the spleen contained a large number of macrophages expressing high reaction for iron. Macrophages with iron granules are mainly located in the splenic cords, and the cells are evenly distributed in the immediate vicinity of the injury of body, and in other parts of the spleen (Fig).

Thus, hyaluronic acid promotes proliferation accelerates synthetic activity of fibroblasts marginal zone of the injured of the capsule and trabeculae of the spleen, ensuring the formation of granulation tissue angiogenesis, prevents inflammation and adhesions. The use of hemostatic plate has no toxic effect on macrophages, keeping the metabolism of iron. The combination of the two components in the plate was allowed to achieve coagulation and adhesion properties, which stimulates fibroblastic activity and accelerates the formation of granulations.

The method of surgical treatment of Tr is maticevski damage to the spleen, carried out by applying the hemostatic film on a damaged spleen, characterized in that as a hemostatic material used film based on hyaluronic acid (ha), chemically related to 5-aminosalicylic acid and impregnated with iron, General structural formula

the degree of substitution of carboxyl groups of 5-aminosalicylic acid is from 30 to 50 mol.%.



 

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