RU2338525C1 - Method of restoration of sensitivity of thrombocytes to agonists in conditions of metabolic syndrome - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention concerns restoration of sensitivity of thrombocytes to agonists, i.e. to aggregation inductors at a metabolic syndrome (MS). For this purpose within 3 months carry out the complex therapy including individually picked up hypohigh-calorie diet, the dosed out physical trainings, and also administration of diltiazem on 90 mg 2 times a day and perindopril on 4 mg of 1 times a day in the morning.

EFFECT: decrease of risk of a thrombogenesis at patients metabolic syndrome at the expense of normalisation of sensitivity of thrombocytes to aggregation inductors.

1 ex, 3 dwg, 2 tbl

Description

The invention relates to medicine, namely to hematology.

Analogues of the proposed method for the normalization of increased sensitivity of platelets to aggregation inducers in patients with metabolic syndrome (MS) do not exist.

There are recommendations in the literature on the appointment of a low-calorie diet and physical training for metabolic correction in the metabolic syndrome (Almazov V.A., Blagosklonnaya Y. V., Shlyakhto E.V., Krasilnikova E.I. Metabolic cardiovascular syndrome. St. Petersburg. : Publishing House of St. Petersburg State Medical University. 1999. - 208 pp.) And reducing the degree of abdominal obesity, which is its component, using recommendations that are more focused on the use of a low-calorie diet (Savelyeva L. Modern approaches to the treatment of obesity. // Doctor, 2000, No. 12, - p. 12-14; Kadyrova R. ., Salhanov BA Power in obesity Alma-Ata "Kazakhstan", 1990), or physical training (Moshkov VN Fitness obesity M .: Medicine, 1976. -.. 56)..

To correct metabolic disorders in patients with metabolic syndrome and abdominal obesity, a siophore is used (Dedov I.I., Butrova S.A., Mishchenko B.P., Dzgoeva F.Kh. Use of metformin (siofor) in patients with abdominal type of obesity. // Problems of endocrinology. 2000. - T.46, No. 5. - S.25-29).

In patients with MS, diltiazem and perindopril are used to correct arterial hypertension.

However, never before has a complex consisting of an individually selected hypocaloric diet, dosed physical training, diltiazem and perindopril been used in patients with metabolic syndrome to normalize their increased sensitivity of platelets to inducers of aggregation of adenosine diphosphate (ADP), collagen, thrombin, adrenaline inducers - ADP + adrenaline, ADP + collagen, adrenaline + collagen.

The aim of the invention is the normalization of increased sensitivity of platelets to aggregation inducers in patients with metabolic syndrome.

The essence of the proposed method lies in the fact that after taking blood, stabilizing it with sodium citrate 3.8%, separating blood into plasma and red blood cells by centrifugation to obtain platelet-rich plasma (BTP) on slides, platelet aggregation tests with several inductors and their combinations. Visual assessment of platelet aggregation under these conditions allows with a small volume (0.02 ml) of plasma and a small volume of inducers to evaluate the sensitivity of platelets to aggregation inducers by the development of the aggregation process. With an increase in their sensitivity to inducers, which is recorded by reducing the inducer dose required for aggregation with its isolated use or in a double combination, it is possible to carry out its correction using a hypocaloric diet, physical training, diltiazem 90 mg 2 times a day, and perindopril 4 mg 1 time in the morning.

The inventive method is as follows. After taking 9 ml of blood in 3.8% sodium citrate from patients with MS, a ratio of 9: 1 was centrifuged for 5 min at 1000 rpm to obtain BTP. Part of the plasma is taken, and the remaining centrifuged at 3000 rpm for 20 min, receiving platelet-poor plasma (BeTP). BTP is standardized by the number of platelets by diluting the original BTP with an autologous BeTP sample (up to 200 · 10 ⁹ / L).

From the resulting volume of standardized plasma, 0.02 ml of plasma is selected for each inductor and the studied combination of inductors. The remaining plasma volume can be used for other hematological and biochemical studies.

From the selected volume of standardized plasma, 0.02 ml of plasma and solutions of one or two inductors (FIGS. 1 and 2) with a total volume equal to the volume of the plasma are applied to a glass slide. When using one inductor, its volume is 0.02 ml, when using two, 0.01 ml each.

As agonists, it is possible to use ADP, collagen, thrombin, adrenaline and combinations of ADP + adrenaline, ADP + collagen, adrenaline + collagen, the necessary doses of which in this case were lower than with their isolated use. The doses of inducers necessary for aggregation in calves with dyspepsia, and the minimum mutually potentiating doses of inducers in them are lower than standard ones (Tables 1 and 2), which can cause platelet aggregation in healthy calves. Plasma is mixed with inducers with a glass rod and the stopwatch is turned on. The mixture is stirred so that the liquid occupies a circle with a diameter of about 2 cm (figure 3). Shaking the glass in a circular motion in the transmitted light of the illuminator, on a black background they monitor the occurrence of aggregates through a magnifying glass. When distinct aggregates appear, the solution becomes clear and some of the aggregates adhere to the glass, the stopwatch is turned off, fixing the time of platelet aggregation.

From the presented material it follows that, compared with stimulation with one inducer in healthy people, when used in individuals with MS and especially two inductors, a much lower concentration of agonists is required for the development of aggregation, which is likely due to the involvement of several activation mechanisms. It should be noted that the study of the aggregation ability of blood plates with two inductors models the events occurring in the bloodstream in the area of vascular damage and the initiation of the hemostasis process. So, in patients with MS, the patterns found are even more pronounced than in healthy people, due to the increased sensitivity of platelets to aggregation inducers with a lower concentration of inducers necessary for the development of aggregation of blood platelets.

Table 1. Doses of inducers that cause platelet aggregation in their isolated use. Inductors ADF, M Adrenaline, M Collagen dilution of the main suspension Thrombin, units / ml Healthy people, n = 128 0.5 × 10 ^-4 5.0 × 10 ^-6 1: 2 0.125 Patients with MS, n = 119 10 ^-4 -6.0 × 10 ^-6 10 ^-6 -5.0 × 10 ^-7 1: 2.2-1: 3 0,110-0,120 table 2 Minimum mutually potentiating concentrations of aggregation inducers when combined with any agonist. Examined Category ADF, M Adrenaline, M Collagen dilution of the main suspension Thrombin, units / ml Healthy people, n = 128 10 ^-6 2.5-10 ^-7 1: 4 0,100 Patients with MS, n = 119 5.0 × 10 ^-7 -5.0 × 10 ^-8 10 ^-7 -3.0 × 10 ^-9 1: 4,5-1: 8 0,090-0,075

It is possible to diagnose hypersensitivity to aggregation inducers in people with the development of platelet aggregation using isolated inducers in doses for ADP below 0.5 × 10 ^-4 M, adrenaline below 5.0 × 10 ^-6 M, collagen below 1: 2, the dilution of the main suspension and thrombin is below 0.125 u / ml, and with their double combination for ADP it is below 10 ^-6 M, adrenaline is below 2.5 · 10 ^-7 M, collagen is lower than the dilution with the main suspension is 1: 4, thrombin - below 0.100 u / ml. In patients with MS, the minimum doses of inducers that can cause platelet aggregation, in the case of using one agonist or two at the same time, are presented below in Tables 1 and 2.

When detecting an increased sensitivity of platelets to aggregation inducers, patients with MS should be prescribed a hypocaloric diet, dosed physical activity, diltiazem 90 mg 2 times a day, and perindopril 4 mg 1 time in the morning.

To create a negative energy balance in the body of patients, they are recommended an individually selected hypocaloric diet.

The caloric content of the daily diet individually for each patient with MS is calculated in kcal according to the formula:

for women 18-30 years old (0.0621 × body weight, kg + 2.0357) × 240,

31 years-60 years (0.0342 × body weight, kg + 3.5377) × 240,

over 60 years old (0.0377 × body weight, kg + 2.7545) × 240,

for men 18-30 years old (0.0630 × body weight, kg + 2.8957) × 240,

31 years-60 years (0.0484 × body weight, kg + 3.6534) × 240,

over 60 years old (0.0491 × body weight, kg + 2.4587) × 240.

The coefficient obtained remains unchanged with minimal physical activity, multiplied by 1.3 for moderate and 1.5 for high physical activity (as a rule, in patients with MS the level of physical activity is low).

3 main meals and 2 intermediate meals are recommended. With the regular skipping of one of the main meals, the frequency of obesity increases significantly, a positive correlation between obesity and skipping breakfast is also revealed. The following daily calorie distribution is recommended: breakfast - 25%, 2nd breakfast - 10%, lunch - 35%, afternoon tea - 10%, dinner - 20%.

To compile the patient’s menu, special tables are used with indications of the chemical composition and calorie content of the products, given that the main sources of energy are proteins (1 g contains 4 kcal), fats (9 kcal), carbohydrates (4 kcal) and alcohol (7 kcal).

The second component of the proposed method is feasible regular physical training.

In real life conditions, it is possible to carry out three forms of physical activity: 1) morning hygienic gymnastics (exercise); 2) therapeutic and preventive gymnastics; 3) fractional physical exercises throughout the day.

1. Morning hygienic gymnastics (exercise).

Morning exercises should be done after sleep before breakfast in a ventilated room. Under the influence of classes, the body is freed from the state of inhibition of physiological processes that occurs during sleep.

The sequence of exercises involves alternating the load on various muscle groups (arms, legs, body). Exercises are performed with a gradually increasing excursion of breathing, stretching, limited use of force conditions. The breathing during exercises should be free, rhythmic, without delay, mainly through the nose; the exhalation should be longer than the inhalation (inhalation 2-3 s, exhale 3-5 s).

With good health, the load can be strengthened by the number of repetitions, speeding up the pace, increasing the amplitude of movements and reducing pauses between exercises.

With fatigue, you should reduce the load, increase the duration of pauses between exercises, fill them with calm breathing.

After gymnastics, you need to go to a wipe or take a shower.

Morning exercises should cause a sense of vitality, increased activity, better health and performance.

If you feel unwell, develop shortness of breath or pain in the heart and behind the sternum, you should temporarily interrupt classes and consult a doctor.

During the day, patients with MS are recommended preventive gymnastics. Depending on the initial training, it is possible to use at the beginning of a lightened version of physical activity, and subsequently a strengthened version.

2. Complexes of therapeutic and preventive gymnastics for persons suffering from MS.

2.1. A lightweight version of therapeutic gymnastics.

Exercise 1. Standing. Walking is calm with a gradual acceleration and deceleration of 1-2 minutes. During the exercise, a gradual deepening of breathing.

Exercise 2. Circular movements in the shoulder joints. When breeding - inhale, while mixing - exhale with a slight tilt of the body and retraction of the abdominal wall - 6-8 times. Fingers touch shoulders, elbows pressed to the body.

Exercise 3. Standing, hands on the belt. Alternately transferring the severity of the body from one leg to the other with slight bending of the legs in the knee joint, without taking the feet off the floor. Do the exercise 10-16 times with muscle tension in the legs.

Exercise 4. Standing, legs spaced shoulder width apart, hands on the belt. Torso forward, touch left sock with your right hand. 4-6 times alternately. When the position is straightened, inhale; when tilted, exhale. Looking forward.

Exercise 5. Standing, arms along the torso. At the same time, take straight arms and one leg to the sides with alternating leg abductions. 4-6 times in each direction alternately. A wave of arms and legs, breathing free, do not hold.

Exercise 6. Standing, legs to the sides, hands in front of the chest, palms down. With the turn of the body, spread your arms to the sides with the turn of the palms up - inhale. Return to the starting position with a slight tilt of the body forward - exhale. 3-5 times in each direction alternately. Coordinate breathing with the movement of the body and hands. By the end of the exhalation, retract the wall of the abdomen.

Exercise 7. Standing, hands free. Walking freely - 1 min, then with high flexion of the hips - 10-20 movements, followed by a transition to a quiet walk - 1-2 minutes. Rhythmic breathing, medium depth.

Exercise 8. Sitting on the edge of the chair, hands on the waist. Bending back and bending forward of the body. Repeat 6-10 times. Do not hold your breath.

Exercise 9. Sitting on the edge of the chair, focus with tassels on the edge of the chair, and with your feet somewhat in front of the chair. Squats with an emphasis on the edge of the chair - 4-6 times. When squatting, exhale.

Exercise 10. Standing sideways to the back of the chair, hold on to it with one hand. Swing your free straight arm with your legs back. Return to starting position. Repeat 4-6 times with each hand and foot. Do not hold your breath.

Exercise 11. Standing, legs apart, arms at the waist. Turns the body to the right and left - 6-10 times alternately. Do not turn your head, look forward.

Exercise 12. Standing, legs together, arms down. To spread your arms to the sides - inhale, bend your leg at the knee and press your hands to your stomach - exhale. 3-5 times each leg in turn. Strive to maintain balance; as you exhale, draw in your stomach.

Exercise 13. Standing, legs together, hands down. Lateral slopes of the body with bending of the opposite arm ("pump"). Do not hold your breath, strive for a greater excursion of movement.

Exercise 14. Standing. Walking is calm with uniform breathing of medium depth. 1-2 minutes

Exercise 15. Lying on a rug with a pillow placed under the head. Go to the half-sitting position and hug the bent hips - exhale, return to the starting position - inhale. Do not hold your breath. Strive in a half-sitting position to maintain balance. Run 4-6 times.

Exercise 16. Lying, arms to the sides, legs apart. Semicircular movements with the right straight leg to the left with the turn of the pelvis - exhale - return to the starting position - inhale. 3-5 times in each direction. Alternately left and right with the greatest possible excursion of the leg movement, while maintaining the emphasis of the hands on the floor.

Exercise 17. Sitting on the floor: a) get on all fours; b) move to a kneeling position; c) raise your hands up - inhale, tilt the body, and take your hands back - exhale. When tilting, belly retract. Repeat 4-6 times; e) move to a standing position, and then to a prone position; f) self-massage of the abdomen with small semicircular movements in a clockwise direction - 1-2 minutes. Rest 2 min; g) calm breathing; h) exercise in protruding (calm) and retracting (active) the abdominal wall. Combine abdominal retraction with expiration through the mouth. Repeat 4-6 times.

Exercise 18. Standing, arms bent. Vigorous walking on the spot or in a room with high flexion of the hips and waved arms - 20-30 steps. Do not hold your breath.

Exercise 19. Sitting on a chair, legs apart, hands on the waist or rest against the edge of the chair. Circular movements of the pelvis with retraction of the abdomen when the pelvis is brought back. 4-6 times in each direction.

Exercise 20. Standing. Calm walking with breathing of an average depth of 2-3 minutes.

With the initial sufficient training or exercise tolerance arising during the classes, the following set of exercises can be used.

2.2. A reinforced version of therapeutic gymnastics.

Exercise 1. Standing. Walking calm with rubbing the palms of the chest, abdomen, lower back. It takes 1-2 minutes.

Exercise 2. Standing, arms down. Simultaneous bending with tension and free “throwing” of arms forward, to the sides and up 12-16 times. When bending, exhale; when leveling, inhale.

Exercise 3. Standing, arms at the waist, legs shoulder width apart. Lateral movements of the pelvis to the right and left, back and forth. It is performed 6-10 times alternately. Breathing is free.

Exercise 4. Standing, feet shoulder width apart, arms down. Circular movements of straight arms in the shoulder joints, 6-10 times with maximum excursion, do not hold your breath.

Exercise 5. Standing, arms in front of the chest, bent at the elbows. Walking with high flexion of the hips, with the touch of hands. 6-10 times each leg in turn. The movements are vigorous, while flexing the thigh - exhale through the mouth.

Exercise 6. Walking calm 1-2 minutes.

Exercise 7. Sitting on the edge of the chair, hands on the waist. Bending and bending of the body. The exercise is performed 8-10 times. The movements are energetic. When straightening, inhale; when bent, exhale.

Exercise 8. Standing sideways to a chair, hold on to the back, the other hand at the waist. Alternating swings with a straight leg forward with the greatest possible excursion. Leg sweep combined with exhalation. It is carried out 4-6 times.

Exercise 9. Standing, legs apart, arms to the sides. Tilts the body forward with a touch of the right brush of the left toe of the foot, the other hand is pulled up. Return to starting position. Combine the slope with the exhale, while straightening, inhale 4-6 times.

Exercise 10. Walking calm with breathing of medium depth. 1-2 minutes

Exercise 11. Standing, hands in a fist and lowered: a) bending the arms at the elbows with force and unbending them with the back, with the greatest possible straightening and tension and a delay in tension for 2-3 seconds. Standing, hands on the waist; b) half-squats, followed by lifting on toes and straining the legs. The exercise is performed 4-6 times with the greatest possible rectification and tension and a delay in the stress state for 2-3 seconds.

Exercise 12. Sitting on the edge of a chair. In the position of the leg raised and bent at the knee joint, alternately shake the tibia and thigh muscles with the hands. Reduce muscle tension. 1-2 minutes

Exercise 13. Sitting on the edge of the chair, straight legs divorced. Breeding and mixing straight arms and legs. When breeding, inhale, while mixing, exhale. It is carried out 4-8 times.

Exercise 14. Standing. Walking is calm with the transition to a rhythmic calm run (jogging) in place or with movement. If tired, go for a walk with moderate breathing. 2-5 minutes

Exercise 15. Lying on the mat. Simultaneous lifting of the body and legs as you exhale. 4-6 times. Arms and legs straightened, keep balance.

Exercise 16. Lying on the mat, emphasis with brushes on the floor. Cross movement with straight legs - “scissors”. 4-8 times. Do not hold your breath.

Exercise 17. With a quick straightening of the legs, move to a sitting position, then lie down. You can help with a wave, 4-6 times.

Exercise 18. Lying on your back, legs bent. Calm breath 4-6 times.

Exercise 19. Lying on your back, arms spread apart with the emphasis of the hands on the floor. With the turn of the pelvis to the left, bend the legs, turn the pelvis with the legs crossed to the right and stretch the legs. Repeat such circular movements with legs 3-6 times in each direction alternately. Do not tear your hands off the floor. Do not hold your breath.

Exercise 20. Lying on your back, arms and legs apart. Alternate turns of the body to the right and left with the laying of one hand on the other. Do not move your legs. With arms apart, inhale, while turning, exhale. It is carried out 3-6 times.

Exercise 21. Lying on your back, arms along the body: a) turn on your left side; b) turn on the right side; c) go to the supine position; d) get on your knees; e) move to a standing position; f) walking in a place with high hip flexion and arm movement - 20-30 steps; g) sit on the mat; h) lie on your back, calm breathing. Repeat the whole complex 3-4 times.

Exercise 22. Standing. Walking calm with breathing of medium depth - 1-2 minutes.

Exercise 23. Standing, legs spaced the width of the foot, hands on the waist. Circular motion of the pelvis, right and left 6-8 times. Do not hold your breath.

Exercise 24. Standing with legs wide apart, hands in front of the chest. Alternately bending the leg with the transfer of body weight to it with stretching the arms to the toe of the bent leg. 4-6 times in each direction. The other leg is straight. When straightening - inhale, while tilting - exhale.

Exercise 25. Standing, legs spaced shoulder width apart, arms at the waist. Circular head movements 4-10 times in each direction.

Exercise 26. Standing, legs spaced shoulder-width apart, arms at the waist. Tilt the body to the right, pulling the left hand up - inhale. Return to starting position - exhale. 4-6 times alternately.

Exercise 27. The same, arms to shoulders. Circular movements of the hands with a maximum excursion in the shoulder joints, when breeding - inhale, while reducing and retracting the walls of the abdomen - exhale. The breath is deep.

Exercise 28. Standing. Calm walking and breathing of medium depth. Reduced overall load. 1-2 minutes

3. Fractional exercise throughout the day.

A patient with MS is a patient with a number of concomitant disorders and, above all, the cardiovascular system. This circumstance limits the simultaneous use of great physical activity in the process of morning gymnastics, as well as in the main occupation of therapeutic and prophylactic gymnastics. That is why an increase in the physical activity of people suffering from MS should be carried out by distributing physical activity in small doses throughout the day. This method of increasing the physical activity of patients with MS should be considered as a fractional load method.

Depending on the real life conditions of patients with MS suffering from various degrees of abdominal obesity, various exemplary fractions of various loads can be recommended to increase physical (motor) activity throughout the day.

Option 1.

Exercise 1. Sitting - spread your elbows to the sides - inhale, stretch your arms forward with tension - exhale, 4-6 times.

Exercise 2. Sitting - stand up with the deflection of the body and sit down - 8-10 times.

Exercise 3. Sitting - an imitation of the movements of a boxer with a possibly large rotation of the body - 10-12 times.

Option 2

Exercise 1. Standing - walking with high hip flexion - 16-30 times.

Exercise 2. Standing - circular movements of the head to the right and left - 3-8 times in each direction.

Exercise 3. Standing - legs spread apart - imitation of the movement of the pigtail - 10-12 times.

Exercise 4. Sitting - transition to a standing position - 10-12 times.

Option 3

Exercise 1. Walking is calm - 1 min.

Exercise 2. Walking accelerated - 1 min.

Exercise 3. Walking with a high flexion of the hips and alternate wave of hands 20-30 times.

Exercise 4. Walking calm with breathing - 1-2 minutes; the run is calm on the spot or with movement around the room - 2-5 minutes.

Option 4

Walking walk of various extent.

Option 5

Physical labor in various versions and of various durations depending on the conditions (cleaning the premises, home maintenance, work on cleaning the territory, garden works, etc.).

In addition to individually selected non-drug treatment, patients with MS should be prescribed diltiazem 90 mg 2 times a day and perindopril 4 mg 1 time in the morning.

The method allows to normalize the sensitivity of platelets to aggregation inducers in patients with MS within 3 months of treatment, translating it to a level characteristic of healthy people. Subject to the following recommendations, it is possible to exclude an increase in the sensitivity of platelets of MS patients to aggregation inducers, which will significantly reduce the risk of thrombotic complications, prolonging their life.

Example. Patient M. 53 years old, 74 kg (body mass index of 29.7 kg / m ^2), age 8 MS examined in outpatient settings. Blood was taken from the patient and examined with an estimate of the minimum dose of inducers, causing platelet aggregation with a number of isolated inducers and their combinations. A decrease in the doses of isolated inducers necessary for the development of platelet aggregation was detected (ADP 4.0 × 10 ^-5 M, collagen 1: 2.5 dilution of the main suspension, 0.120 u / ml thrombin, 5.0 × 10 ^-7 M adrenaline) and their double combination (ADP - 10 ^-7 M, collagen 1: 5 dilution of the main suspension, adrenaline -10 ^-7 M, thrombin 0.090 u / ml), which indicated an increase in the sensitivity of platelets to aggregation inducers.

The patient was prescribed a complex of a hypocaloric diet (1736.4 kcal), physical training, diltiazem 90 mg 2 times a day, and perindopril 4 mg 1 time in the morning. This allowed after 3 months to reduce body weight (65 kg body mass index of 26.1 kg / m ²⁾ and a fully normalized sensitivity to inducers of platelet aggregation. When using isolated inducers and their combinations, the concentration necessary for aggregation corresponded to the norm (ADP 0.5 × 10 ^-6 M, collagen 1: 2 dilution of the main suspension, thrombin 0.125 u / ml, adrenaline 5.0 × 10 ^-6 M), with a double combination - ADP 10 ^-6 M, collagen 1: 4 dilution of the main suspension, adrenaline 2.5 × 10 ^-7 M, thrombin 0.100 u / ml, which eliminated the risk of thrombotic disorders.

Compliance with the recommendations given to patients made it possible to subsequently prevent recurrence of increased platelet sensitivity to aggregation inducers and mitigate the risk of platelet disturbances.

Claims (1)

A method of restoring platelet sensitivity to aggregation inducers in the metabolic syndrome by applying an individually selected hypocaloric diet, dosed physical training, 90 mg diltiazem 2 times a day, and 4 mg perindopril 1 time in the morning.

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