RU2279144C2 - Method for modeling femur and pelvic bone anomaly - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: method involves cutting femoral artery branches and acetabular artery in rats to achieve round ligament blood vessels proliferation into femur neck.

EFFECT: usability as basis for developing human bone disorder prophylaxis and treatment methods.

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Description

The present invention relates to medicine, namely to orthopedics, and can be used to model congenital diseases of the femur and pelvic bones, for example, congenital dislocation of the femur in children, which will serve as the basis for developing methods for the prevention of congenital bone pathology in humans.

Known methods for modeling femoral and pelvic dysplasias allow to obtain diseases of the bones of the hip joint by disrupting the integrity of the vessels that feed the bones in the early stage of the postnatal vertebral period, which in the chronic course of the disease can be interpreted as anomalies of the skeleton bones. These models of diseases can be implemented both conservatively and operatively.

Known methods of disturbance of intraosseous vessels immediately after hatching of chicks from eggs or the birth of mammals, justify the use of the proposed method of modeling, impaired development of intraosseous vessels by crossing them, because at the time of the intersection of the vessels, their structure corresponds to that during the period of fetal development, in which congenital underdevelopment of the vascular system of animals occurs, and which are detected after its birth.

With more severe surgical interventions on the elements located in the zone of the hip joint, there is also a violation of the vessels located in the tissues. For example, when crossing a joint capsule, the integrity of the vessels passing through it and providing nutrition to the femoral head in mature individuals is violated (1).

Known methods for the pathological development of bones by ligation and compression of regional vessels, when they are shortening and deformation (2).

Numerous modern methods for modeling osteochondropathies are known, which allow obtaining abnormal bone development when animals reach adulthood. But these changes in bone pathogenesis cannot be attributed to skeletal abnormalities, because they are carried out on bones, the pineal glands of which have bone tissue, bone marrow and blood vessels. Their presence in the pineal glands indicates the absence of intrauterine disorders of the development of the skeleton and the possibility of modeling such diseases in animals in the postnatal period.

A known method of modeling osteodysplasia in animals (3). It consists in the fact that after hatching the pigeon chicks, they perform the intersection of the diaphyseal artery of the tibia. This leads to a delay in bone growth, prolonged preservation of cartilage in the zone of the pineal gland and a delay in the formation of bone nuclei in the lower pineal gland. All this is characteristic of osteodysplasia of the tibia. On the femur, this picture is regarded by clinicians as the first stage of development of a congenital dislocation of the hip.

However, modeling of this disease in birds is impossible, because in evolution and ontogenesis, they do not have the development of bone nuclei in the femur, which occurs in mammals. Therefore, in birds, intersection of the arteries of the head ligament will not contribute to the development of osteodysplasia. Their bone tissue comes to the head from the diaphysis with the growing branches of its artery.

Known methods for the formation of aseptic necrosis of the femoral head, the use of which could lead to the development of abnormalities of the bones of the hip joint. For example, a method for modeling aseptic necrosis of the femoral head (4). It consists in the intersection of retinacular vessels of the femoral neck in rabbits aged 2-2.5 months.

However, if you do not go into a deep study of the structure of the vessels of the hip joint, then the use of this method in newborn rabbits could be an analogue of the invention. Based on the anatomical structure and localization of the retinacular arteries, as well as the age of the rabbits used, the use of this method is unsuccessful. In growing animals, the retinacular vessels do not enter the femoral head - this is prevented by the intraarticular cavity of the synovial membrane (5). The retinacular vessels lying in the capsule go either towards the limb, or towards the greater trochanter, where they are forced to go to the periosteum and bone tissue. From the limb, the vessels cannot enter the head through the joint cavity between the head and the cavity. With any movement, the vessels will break, and the evolution of mammals will end.

From the neck, blood vessels can not pass because at the age of 2-3 months. in rabbits, the growth zone is preserved. It inhibits the growth of blood vessels in the head. In particular, in children, it delays vascular growth up to 3 years (6). The effect obtained by the authors is achieved due to other factors.

There is also a method for modeling aseptic necrosis of the femoral head (7). It consists in a paraarticular daily administration for 20-30 days every 6 hours of 0.1% adrenaline solution in an amount of 0.1-0.3 ml. This method is most rational for the formation of diseases of the skeletal system, because theoretically and practically, it delays the nutrition and growth of organs by narrowing the blood vessels, which can also be in the intrauterine development of an individual. But its use on the fruits of animals is technically impossible. It is impossible to use it on newborn rabbits, and even more so in rats because of aggressiveness. The number of manipulations is so great, even for one day, that the animals will leave their offspring without feeding or resort to cannibalism, which is typical for them. Moreover, this method does not solve the main problem, that is, stopping the growth of blood vessels that form bone tissue in the head. Adrenaline acts as a vasoconstrictor, but the growth of blood vessels does not stop at the same time, which underlies the anomalies of the skeleton. The bone core in the head is formed by the vessels of the round ligament, they go from the side of the abdominal cavity. The introduction of a solution into the joint cavity of one-day-old rabbits is practically impossible, and an increase in its concentration or volume may lead to the death of newborns due to a disorder of the cardiovascular system. Baby rats are even less likely to survive, as their birth weight is significantly less. All of the above indicates the impossibility of using this method.

Closest to the proposed method for the formation of anomalies of the femoral and pelvic bones is a method for excising the femoral artery from the pupartic ligament to the femoral-knee canal in newborn rabbits (8).

After violation of the integrity of the femoral arteries in the first and second series of experiments, anomalies of the femur and pelvis were not obtained.

After excision of the femoral vessels in the third and fourth series of experiments, the author noted a shortening of the femur and a decrease in the bone nucleus in the pineal glands. However, 5-8 months after surgery, in the third series of experiments, restoration of the length of the legs and their individual bones was noted

In the fourth series of experiments, where the femoral artery and vein were excised, the restoration of growth of individual bones and limbs did not occur even 17 months after the operation. That is, the author received an anomaly of the hind legs after the growth of the skeleton of a rabbit.

This model of the formation of bone anomalies is taken as a prototype not only for violation of the integrity of the femoral artery, but also, which is no less important, in terms of the duration of the operation, because it is performed on newborn rabbits. During this period, there are no bone nuclei in the femoral head, and the vessels that feed the femoral head and pelvic bone are in an immature anatomical state. In addition, this method automatically turns off the blood supply to the bones with arteries: diaphyseal, envelopes, retinacular, periosteal.

The disadvantage of the above modeling method is that the abnormal development of the femur was obtained with a rough surgical intervention on large vessels of the thigh. Changes in the femur are accompanied by sharp pathological changes in all segments of the leg, which does not happen with congenital dislocation of the femur in children. Surgery is performed on vessels that do not directly feed the head of the growing femur and elements of the acetabular cavity. Changes in the hip joint are inadequate to changes throughout the hind limb. Thus, this model of abnormality cannot be taken to develop methods for treating abnormally developed femur and pelvic bones in humans.

Based on the existing level of knowledge about the structure and development of the elements of the hip joint and its blood supply, the task was to obtain a model of abnormal development of the hip joint in mammals, which is closest to the pathogenesis of congenital dislocation of the thigh in children, and is also less traumatic.

The problem is solved as follows: modeling of the anomaly of the femoral and pelvic bones is carried out by crossing the branches of the femoral artery.

New in solving the problem is that they additionally cross the acetabular artery in breeding mammals, such as rats, before the growth of the vessels of the round ligament in the femoral head.

Explain the salient features of the proposed method.

The intersection of the acetabular artery in breeding mammals, such as rats, before the round ligament vessels grow into the femoral head, allows us to obtain a model of anomalies in the development of the pelvic and femoral bones, which is closest to the pathogenesis of the disease, similar in children, namely, congenital dislocation of the femur.

We conducted experiments on 28 laboratory white rats in which the intersection of the arteries was carried out on the 18th day after their birth. At the same time, it was assumed that in this period the rat pups can independently take food (in case the mother refuses to feed them after the operation). At the same time, the onset of cartilage cell hypertrophy in the femoral head was noted, which indirectly indicates the passage of blood vessels through the femoral head’s own ligament, but they have not yet penetrated into its cartilaginous tissue. It is during this period that it is easier to find the acetabular artery for its intersection.

The connection between the vessels and the growth of cartilage and bone tissue has been established today, therefore, the lag in the development of the femoral head may be due to malnutrition by the vessels coming from the round ligament of the femoral head into its cartilaginous tissue.

Malnutrition during the embryonic period can lead to the later formation of cartilage at the site of mesenchyme and bone tissue at the site of cartilage. This process is considered as the development of chondroosteodysplasia, in which the experimental bone retains its anatomical shape.

After birth, insufficient development of the elements of the hip joint is considered as osteochondrodysplasia, while bone growth is maintained. After the end of bone growth (the disappearance of the cartilaginous epiphyseal growth plate), an irregular anatomical bone is found in the form of a significant reduction in its length, a decrease in its articular end and a change in shape, which is considered as an anomaly in the development of a particular bone. With improper anatomical development of the femur and acetabulum, there is a congenital dislocation of the hip. The disease begins in the prenatal period and, under adverse conditions, ends at the end of the growth of the pelvis and lower limb and can persist until the end of the individual's life.

To model the anomaly, it is important that, normally, the femoral head remains cartilaginous after the birth of the baby for 1-4 months. These terms correspond to the period of preservation of the cartilage tissue in the femoral head in some laboratory animals, for example, rats. To substantiate studies on modeling abnormalities of the pelvic and femur in laboratory rats, we studied the growth of the bones of the femur and pelvis from birth to 1 year. It was found that the cartilage tissue of the femoral head persists in rats up to 60-70 days after their birth. Then a bone core appears in the femoral head. The feeding vessels in the femur are located at the base of the trochanter and femoral head in the amount of 1-3 and the vessels of the round ligament have not yet grown into the femoral head, which corresponds to 17-18 days after the birth of rats.

The patent study on the subclass MKI G 09 B 23/28 and the analysis of scientific and medical information, reflecting the current level of methods for modeling diseases of the hip joint, did not reveal technologies identical to the proposed one.

Thus, the proposed method for modeling the abnormal development of the hip joint is new.

The interconnections and interaction of the essential techniques of the proposed method for the abnormal development of the hip joint ensures the achievement of a new technological result in solving the problem, namely, to provide a less traumatic modeling of congenital dislocation of the femur in mammals, which is closest to a similar disease in children.

The proposed method for modeling abnormal development of the bones of the thigh and pelvis can be widely used in experimental medicine, because can be repeatedly reproduced in any experimental laboratory of a surgical profile.

We conducted experiments on 28 laboratory white rats. Crossing of arteries was carried out on the 18th day after their birth. This was based on the fact that during this period, rat pups can independently take food. This is important if the mother refuses to feed them after surgery. At the same time, the onset of hypertrophy of the cartilage cells in the head was noted, which indirectly indicates the passage of blood vessels through their own ligament of the femoral head, but they have not yet invaded its cartilage tissue. In this period it is already possible to find arteries for their subsequent intersection.

The essence of the proposed method for modeling the abnormal development of the femur and pelvic bones is as follows: in 18-day-old rat pups under light ether anesthesia and under the control of a binocular magnifier with a thin narrow scalpel for microsurgical operations, after treating the skin in the lumbar spine and thigh with a solution of 70 ° ethyl alcohol , make a narrow incision in the projection of the sciatic groove from the inner thigh in the inguinal fold. Carefully pushing the soft tissues with narrow raspators and exposing the bone-cartilaginous surface of the sciatic bone, they find a thin acetabular artery extending from the obturator artery and cross it. This leads to a temporary halt in the growth of blood vessels supplying the acetabular cavity and the femoral head. Then, moving the soft tissues to the top of the greater trochanter, they find the bases of it, the head and the trochanter. Here can be from 1 to 3 nutrient vessels. They lie close to each other, since the bone here is small, which will facilitate their finding and intersection. After that, the edges of the wound are brought together, clamped to each other and treated with a solution of ethyl alcohol. Baby rats are placed in a cage where the mother continues their feeding. Then one-month-old rat pups are transplanted into separate cells. The observation period was 7-365 days from the time of surgery. Withdrawal from the experiment is carried out in pairs of ether every week for 2 months, then every month for 10 months. After euthanasia, the hind legs together with the pelvis are isolated and placed in a 10% solution of neutral formalin. Then an anatomical study and a histological study of the preparations made according to the generally accepted method from the experimental and control legs of the same rats are carried out.

By an anatomical study, it was found that on the 365th day after the intersection of the acetabular artery and the branches of the femoral artery, the presence of a displacement of the reduced head of the femur relative to the acetabular cavity was revealed. This led to the formation of a disease in rats adequate to congenital dislocation of the hip in humans.

The implementation of the invention is illustrated by examples of the dynamics of the development of anomalies of the growing bones of the thigh and pelvis in breeding mammals, in particular rats, when considering histological preparations and anatomical formations.

Example 1. The age of the rat is 60 days. Operated at the age of 18 days according to the above method. On the histological preparation, underdevelopment of the head of the femur and pelvic bones was noted (see the appendix to the description of figure 1).

The height of the control head of the right femur is 600 μm, the experimental head of the left femur is 450 μm. The height of the growth zones in the experimental and control bones is the same and equal to 100 microns.

In the control head of the femur there is a bone core 400 microns high, in the experimental left head it is absent. Thus, on day 42, osteodysplasia of the femur and pelvic bones was detected, which should be interpreted as the first stage of the development of anomalies of the bones of the hip joint.

Example 2. The age of the rat is 365 days. Operated at the age of 18 days according to the method described above. In an anatomical study of hip and pelvic preparations, i.e. when opening the hip joint, a displacement of the femoral head to the edge of the limb was revealed, due to its small inner diameter (1 mm) and large head diameter (2 mm) (see the appendix to the description of figure 2). The volume of the internal cavity of the cavity decreased due to the growth of chondro-fibrous tissue, which moved the head to the edge of the limb and it is covered with a capsule of fibrous tissue. Such standing of the head with congenital dislocation of the thigh in a person’s children is called lateralization of the head or subluxation. But in this case, we must talk about a complete dislocation, because the head is shifted to the entire depth of the cavity. The displacement of the head up did not occur due to the sparing attitude of the rat to the operated limb and the proliferation of connective tissue in the area of the acetabular roof, which further prevents the displacement of the head up.

In this case, the length of the control bone of the thigh is 33.5 mm, of the experimental bone - 30.0 mm.

The diameter of the control head of the thigh is 3 mm, the experimental - 2 mm. The thickness of the control limb is 0.3 mm, the experimental - 2-2.5 mm. The depth of the control cavity is 3 mm, the experimental - 1 mm. The diameter of the control cavity: outer - 4 mm, inner - 3.4 mm; in the experimental cavity: outer - 5 mm, inner - 1 mm.

Changes in the elements of the femur and acetabulum indicate an abnormal development of the bones of the thigh and pelvis. This suggests that a year after the operation, a model of congenital dislocation of the hip was obtained.

Thus, the proposed “Method for modeling anomalies of the femur and pelvic bones” allows to obtain a model of abnormal development of the hip joint in mammals, which is closest to the pathogenesis of congenital dislocation of the femur in children, and is also less traumatic.

Information sources

1. Kabak S.L., Feshchenko S.P., Anischenko E.P. Osteoarticular system. Morphological and biochemical aspects of formation. - Minsk: Science and technology, 1990. - 181 p.

2. Stekolnikov B.A. The effect of vasoconstriction on the growth of limbs // Orthopedist., Traumatol. and prosthetics. - 1927. - Prince I. - S. 42-46.

3. A.S. USSR No. 1353431, A 61 B 17/56. Bull. inventions, 1987, No. 43.

4. A.S. USSR No. 1668991, G 09 V 23/28. Bull. inventions, 1991, No. 29.

5. Vorobyov V.P. Human anatomy. - M., 1932. - T.I. - 702 s.

6. Latypov A.D. Analysis of the causes of complications of conservative treatment of congenital dislocation of the hip and measures to prevent them. Abstract ... Dr. med. sciences. - M., 1969. - 48 p.

7. A.S. USSR No.2009547. Bull. Inventions, G 09 V 23/28. 1994, No. 5.

8. Leskiv M.V. On the effect of reduced blood circulation of the pelvic limb on the growth of its bones // Archive of Anatomy. - 1969. - Issue 12. - S. 100-104.

Claims (1)

A method for modeling anomalies of the femoral and pelvic bones by crossing the branches of the femoral artery, characterized in that the rats additionally cross the acetabular artery to grow the vessels of the round ligament into the femoral head.

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