RU2626567C1 - Method for legg-calve-perthes disease simulation - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to Legg-Calve-Perthes disease (LCPD) model, which can be used to test various treatments and osteonecrosis prevention agents. The simulation method involves introduction of 0.1% epinephrine in the periarticular tissues of the hip joint at a dose of 0.5 ml daily for 1 month. From the 15th day of preparation administration, tractions are applied additionally to the hip joint, including full flexion with limb subsequent extension, daily, 10 times of 3 repetitions, for 15 days.

EFFECT: method increases the simulation reliability due to the effect on different parts of disease pathogenesis with decreased invasiveness and risk of animals death.

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Description

The invention relates to experimental medicine, to models of aseptic necrosis of the femoral head (ANGBC), which can be used to test various treatment methods and means of preventing osteonecrosis.

Among the diseases of the musculoskeletal system in children, leading to social maladaptation, osteochondropathy of the femoral head occupies a leading position. Pathology is one of the most common and disabling orthopedic diseases accompanied by aseptic necrosis of bone tissue. The high prevalence of the disease, the frequent onset of disability at a working age, the need for long and expensive treatment are the main factors that determine the medical and social significance of this pathology. The most relevant study of the lesion of the femoral head, since it significantly affects the quality of life of patients. For a full study and testing of new methods of treating this pathology, a scientist needs to work out all the stages in an animal experiment. This requires the creation of a model of osteonecrosis of the femoral head in the experiment.

In the course of studying the literature, methods for modeling ANGBC on various experimental animals (rats, rabbits, dogs) were identified. The type of animal does not matter, since in all the proposed methods there is a pathogenetic effect on bone tissue, which is of the same type by its anatomical and pathomorphological nature. The difference is only in the proportion of drugs used depending on the weight of the experimental animal [7].

The following are the most famous methods for the formation of aseptic necrosis of bone tissue in the experiment. In the studied literature, there are two main types of the formation of ANGBC in animals in the experiment - these are invasive methods (surgical interventions) and non-invasive (manipulations). The following are operational methods.

The history of the creation of the ANGBC model in an invasive way begins with the work of prof. G.S. Kilchevsky. As early as 1963, a method was proposed for modeling aseptic necrosis of the femoral head. In this method, an intracapsular circular section of the synovial membrane at the base of the neck and ligation of the round ligament are performed. However, the method is invasive, has great trauma and the risk of infection of the joint [4].

Colleagues from the Kharkov Research Institute of Orthopedics and Traumatology under the direction of V.A. Filipenko in 1982 proposed a method for modeling aseptic necrosis of the femoral head, in which they offer direct exposure to liquid in the upper thigh of the experimental animal with liquid nitrogen twice with a cryoprobe with a temperature of 100 degrees at the border of the cartilaginous cover of the head for 5 minutes with an interval of 4 weeks. The authors note the positive results of the proposed method [13].

A number of works are devoted to the study of intraosseous pressure in the pathogenesis of osteonecrosis of the femoral head. So, in 2004, a team of authors led by prof. I.V. Kirgizova proposed a method for creating a model of osteochondropathy of the femoral head in an experiment. Changes in the bone structure characteristic of Perthes disease were achieved by increasing intraosseous pressure. The study was conducted on 10 outbred dogs aged 4-6 months. Around the femur was a sterile stainless steel clamp. The clamp was tightened to compression of the periosteum [5]. However, this version of the model of aseptic necrosis has a major drawback - it is technically complicated due to the need for surgery. Later, in 2008, Kirpichev S.V. defended a thesis of a candidate of medical sciences on the subject “The influence of the value of intraosseous pressure in the femoral head on the formation and choice of surgical treatment of Perthes disease”. In his study, the author proposes a technique for measuring intraosseous pressure in the metaepiphyseal sections of the tubular bones. For the first time, information has been obtained on the relationship between the value of intraosseous pressure and the morphological structure of bone tissue in normal children in various age groups and in osteochondropathy of the femoral head. By changing the intraosseous pressure, it was possible to achieve positive results in the treatment of Perthes disease. The author notes that the application of the proposed method of treatment in the clinic has a positive trend in the pathogenesis of the disease [6].

Tatyanchenko V.K. et al. They proposed a method for modeling aseptic necrosis of the femoral head: The authors propose to inject talcum powder into the joint cavity and to inject subperiosteal coal tar preparation. The method is supplemented by alcoholization of the sacral plexus with 96 ° alcohol. The authors note that after 2 months the animal develops 1 degree of aseptic necrosis of the femoral head, and after 3 months, II degree, and after 4.5 III degree. However, for the implementation of this experiment, access to the joint is necessary, which has the likelihood of inflammatory complications. The authors in the cited publication insist on the main value of the method - the possibility of creating a specific stage of the ANGBC in the experiment. We believe this is not so relevant, since the most promising joint-preserving operations are relevant in the early stages of the disease, while radical (endoprosthetics) are considered operations of “despair”, when the joint can no longer be saved [12].

Colleagues from St. Petersburg Medical University. I.P. Pavlov led by Rasulov P.M. in 2009, a method was published for modeling aseptic necrosis of the femoral head in laboratory animals, including the traumatic effect of opening the hip joint in stages, intersecting the capsule and the round ligament of the hip joint, circular intersection of the neck with removal of the periosteum around the entire perimeter of the neck. The authors note the high reliability of the proposed method. However, its technical and surgical complexity is obvious [10].

In 1986, Gafarov Kh.Z. and co-authors published their experimental studies in the journal Orthopedics and Traumatology on the formation of ANGBC by perforating a sprout plate. The authors proposed tunneling of the femoral neck, followed by perforation of the growth plate and pineal gland with a Kirschner spoke. According to the authors, as a result of this method, a reliable model of osteonecrosis is formed [3]. However, this method does not adequately carry out postoperative femoral head devascularization, as well as multiple damage to the growth plate leads to impaired bone growth and coxarthrosis.

A known method of creating a model of osteonecrosis by disrupting arterial blood supply to bone tissue by creating artificial thrombosis of intraosseous vessels. Thrombosis was created by introducing into the main artery feeding the bone a 50% suspension of finely divided metallic silver in a 2% solution of sterile gelatin until it became completely clogged [11].

Many authors propose methods for ischemia by creating conditions for the violation of blood supply to the head vessels. A number of works are devoted to the alcoholization of nerve plexuses or blood vessels. Pozharsky V.P. et al. in 2007 proposed the introduction of a needle with a mandrin into a test animal (rabbit) into the studied pineal gland under general anesthesia under aseptic conditions. After extracting mandrena from it, 1 ml of a mixture consisting of equal parts of 10% calcium chloride and 96% ethyl alcohol is injected through a needle. The authors explained that the method reproduces an adequate model of aseptic necrosis of the bone tissue of the pineal gland [9].

In 2006, Boyko A.S. He published dissertation research in which he described the method of forming a model of ANGBC, which consists in introducing an experimental animal thrombovar into the subepiphyseal area of the femur. The author insists on a pathogenetically substantiated experimental model of ANGBC. Based on the developed experimental BLKP model, it was proved that one of the main links in the pathogenesis of aseptic necrosis of the femoral head is local hypercoagulation syndrome with impaired venous outflow from the proximal femur epimetaphysis [2]. This pathogenetically substantiated method has much in common with the prototype proposed below from the point of view of the fundamental approach.

Known methods described in patent information sources using the introduction of a solution of adrenaline into the paraarticular tissues of the studied joint of an experimental animal. In 2006, at P.N. P.N. Harmful ”under the supervision of the head of the experimental laboratory, MD Netylko G.I. A method for reproducing a model of segmental osteonecrosis (aseptic necrosis) of the condyles, knee joint in rats was published. The method includes daily paraarticular administration of adrenaline to an animal with age-related osteoporosis and renal osteodystrophy. In this case, 0.2 ml of a 0.1% solution of adrenaline is administered for 6 weeks and twice a week intraarticularly under the patella 0.12 mg of methylprednisolone. The authors note that the method allows you to create a polyetiological experimental process based on impaired microcirculation and venous outflow of the proximal femur [8]. However, the requirements for renal dystrophy complicate the model, as does the need for age-related animals to participate in the experiment.

Closest to the claimed, taken as a prototype, is a method for modeling aseptic necrosis of the proximal epiphysis of the femur, proposed S.S. Berenstein. The author created zones of chronic ischemia with the subsequent development of osteonecrosis of the femoral head in rabbits by daily administration of 0.1-0.3 ml of 0.1% adrenaline into paraarticular tissues after 6 hours for 20-30 days [1]. However, the obvious drawbacks of the method are: the complexity of technical performance in the form of frequent administration of the drug (every 6 hours for a month), this brings additional suffering to the animal, sometimes leading to the death of the experimental animal. The leading disadvantage of this method is the monopathogenetic effect - only on the vascular link of homeostasis.

A new technical result is an increase in the reliability of the method, due to the impact on a greater number of links of pathogenesis, a decrease in the invasiveness and risk of death of the animal.

To achieve a new technical result in a method for modeling aseptic necrosis of the femoral head, including the introduction of 0.1% adrenaline into the periarticular tissues of the hip joint, that adrenaline is administered at a dose of 0.5 ml daily for one month, after which, from 15 days the introduction of the drug additionally carry out traction on the hip joint, which consists in complete flexion followed by extension of the limb, daily, 10 times for 3 repetitions for 15 days.

New in the method is that in the proposed model they produce an effect on two key pathogenesis links - vascular and stress. It is well known that osteochondropathy of the femoral head in children develops as a result of chronic ischemia (vascular link) and excessive physical activity during the growth and maturation of the child (load link). It is no coincidence that the golden rule for treating Perthes disease is to limit the load on the diseased joint [2].

The effect on the vascular link of pathogenesis consists in the introduction of 0.1% adrenaline in a dose of 0.5 ml daily into the tissues of the hip joint for one month.

To administer adrenaline after palpation of the greater trochanter of the right hip joint, a sliding upward movement is performed (towards Spina iliaca anterior posterior) (Figure 1 shows the location and path of insertion of an adrenaline chipping needle).

Further, from the 15th day after the introduction of adrenaline according to the specified scheme, with the appearance of indirect signs of ischemia in the projection of the hip joint (hair loss, peeling of the skin in the area of drug administration), the pathogenesis link is formed daily, which is formed due to physical exertion on the head of the hip joint. The impact includes complete flexion, followed by extension of the investigated limb, which creates pressure on the head of the hip joint and the progression of the ANGBC processes under the conditions of the created regional ischemia of the hip joint. Loads are carried out daily 10 times for 3 repetitions for 15 days.

The proposed method is based on the analysis of the results of experimental studies on rabbits.

Example

At the first stage, 0.1% ADRENALINE (EPINEFRINA) was introduced into the periarticular tissues of the hip joint in a dosage of 0.5 ml daily for 1 month. From 15 days the introduction of the drug was supplemented by traction on the rabbit's hip joint. The impact included complete flexion followed by extension of the test limb, which created pressure on the head of the hip joint. The exercise was carried out daily, 10 times in 3 repetitions for 15 days.

Starting from the first day, the animal felt satisfactory. The pupils did not dilate, the reaction to light against the background of the drug did not suffer. On the part of the respiratory and cardiac contractions, deviations were not noted.

On the 15th day of adrenaline administration, hair loss in the hip joint was revealed, which indicated chronic ischemia of paraarticular tissues at the injection site (Fig. 2a, b).

In FIG. 3 - view of the animal on the 15th day of drug administration: general (a), in the area of the hip joint (b). On day 30, significant hair loss and baldness were observed in the right hip region (Fig. 2a, b).

On the 30th day of administration of the drug, X-ray of the hip joints in direct projection was performed. In FIG. 4a, b shows an overview radiography of the hip joints on the 30th day of drug administration: the contralateral joint (a) and the joint under investigation (b).

On a direct projection radiography of the hip joints, homogenized dimming of the right femoral head in the form of foci of osteonecrosis and spongy osteoporosis characteristic of the initial stage of radiological manifestations of aseptic necrosis of the femoral head was revealed (Fig. 3a). There is a violation of the integrity of the bone tissue by the type of impression fracture (shown by an arrow), which is typical for the second stage of ANGBC (Fig. 3b). The contralateral head of the usual form and structure: a trabecular pattern is traced, the joint space is without pathological changes, homogenized dimming of the head and neck is not observed (Fig. 3a).

Thus, the proposed simulation method is easy to execute 0.1% adrenaline, that adrenaline is administered in a dose of 0.5 ml daily for one month, which ensures reliable formation of a model of osteonecrosis in an experimental animal due to the impact on two links of the pathogenesis of ANGB. The method is minimally invasive, eliminates the use of surgical intervention, which prevents the possible suffering of the animal. Also, in practice, the risk of animal death is reduced. Using the proposed model makes it possible to practice with it the tactics of surgical correction of ANGBC (Perthes disease) in the experiment, which can improve the results of surgical treatment of this pathology in the clinic, and also has high social significance.

Information sources

1. Berenstein S.S. "A method for modeling aseptic necrosis of the femoral head." RF patent №2009547 dated 03.15.1994

2. Boyko A.S. "Comprehensive treatment of Legg-Calve-Perthes disease in children" diss. for the degree of candidate honey. Sciences, Rostov-on-Don, 2006

3. Gafarov Kh.Z., Yusupov R.F. “On the surgical treatment of Perthes disease” // Orthopedics and Traumatology. - 1986. - No. 11. - S. 9-13.

4. Kilchevsky G.S. "Avascular necrosis of the femoral head in the experiment", Orthopedics, traumatology and prosthetics, 1963 - No. 7. - S. 30-34.

5. Kirgizov I.V., Gorbunov N.S., Kirpichev S.V. et al. "A way to create a model of osteochondropathy of the femoral head." RF patent No. 2229167 dated 10/18/2004

6. Kirpichev S.V. “The influence of the value of intraosseous pressure in the femoral head on the formation and choice of surgical treatment of Perthes disease” diss. for the degree of candidate honey. Sciences, Krasnoyarsk, 2008

7. Lopukhin Yu.M. "Experimental Surgery" M .: - 1971. - 283 p.

8. Netylko G.I., Bozhko A.M., Zaitseva M.Yu. et al. "The way to create a model of osteoporosis in a rabbit in an experiment." RF patent No. 2480843 of 04/27/2013

9. Pozharsky V.P., Egorova S.A., Egorov N.A. et al. "A method for modeling epiphyseal aseptic necrosis in an experiment." RF patent No. 2300812 of 06/10/07

10. Rasulov P.M., Kornilov N.V., Bolshakov O.P. "A method for modeling aseptic necrosis of the femoral head in laboratory animals." RF patent No. 2354313 dated 05/10/09

11. Stetsula V.P., Talko I.I., Shtin V.P. et al. “Experimental aseptic necrosis of the humerus in dogs” // Orthopedics and traumatology. - 1963. - No. 7. - S. 74.

12. Tatyanchenko V.K., Ovsyannikov A.V., Sikilinda V.D. et al. “A method for modeling aseptic necrosis of the femoral head” RF Patent No. 2069015 of 11/10/1996

13. Filipenko V.A., Malyshkina S.V., Grandfather N.V. et al. “A method for modeling aseptic necrosis of the femoral head” RF Patent No. 1141444 of 02.23.1085

Figure 1 - place and trajectory of the introduction of the needle for chipping with adrenaline.

Figure 2a, b - view of the animal on the 15th day of drug administration: general (a), in the area of the hip joint (b).

Figure 3a, b - view of the animal on the 30th day of drug administration: general (a), in the area of the hip joint (b).

Figure 4a, b - survey radiography of the hip joints on the 30th day of administration of the drug: contralateral joint (a) and the studied joint (b).

Claims (1)

A method for modeling aseptic necrosis of the femoral head by introducing 0.1% of adrenaline into the periarticular tissues of the hip joint, characterized in that adrenaline is administered in a dose of 0.5 ml daily for 1 month, after which traction is additionally carried out from the 15th day of administration on the hip joint, including complete flexion and subsequent extension of the limb, daily, 10 times in 3 repetitions for 15 days.

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