RU2393835C1 - Method of quick optimisation of thrombocyte sensitivity to aggregation inducing factors in patients with arterial hypertension and impaired glucose tolerance - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to haematology and endocrinology, and concerns normalisation of thrombocyte sensitivity to aggregation inducing factors in the patients with arterial hypertension and impaired glucose tolerance. That is ensured by the integrated treatment including graduated physical activity, including daily swimming in a pool for at least 20 minutes a day, and administration of lisinopril in dosage 10 mg once a day in the morning and metformin in dosage 500 mg once a day. The therapeutic course is at least 5 weeks.

EFFECT: complex of specific medical products and physical activity combined with empirically prescribed length of treatment provides complete normalisation of thrombocyte sensitivity to aggregation inducing factors that in turn reduces risk of thrombolytic complications in the given group of patients.

1 ex, 3 dwg, 2 tbl

Description

The invention relates to medicine, namely to hematology and endocrinology.

Analogues of the proposed method for the normalization of increased sensitivity of platelets to aggregation inducers in patients with arterial hypertension (AH) with impaired glucose tolerance (NTG).

There are recommendations in the literature on the appointment of physical training and swimming for metabolic correction in metabolic syndrome elements (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 p.).

Metformin is used in patients with NTG and type 2 diabetes mellitus to reduce insulin resistance.

To correct high blood pressure in hypertension with NTG, lisinopril is used.

However, never before has a treatment complex consisting of dosed physical activity, swimming, metformin and lisinopril been used in patients with hypertension with NTG to normalize their increased sensitivity of platelets to combinations of inducers - adenosine diphosphate (ADP) + adrenaline, ADP + collagen, adrenaline + collagen, ADP + adrenaline + collagen, ADP + adrenaline + thrombin, which can lead to the development of hyperaggregation and vascular microthrombosis, causing deterioration of trophic tissue, the risk of heart attacks and strokes in people with hypertension and NTG.

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

The essence of the proposed method is 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 combinations of inducers are performed. 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 inductors, recorded by reducing the inductor dose required for aggregation when using their double and triple combinations, it is possible to carry out a correction using dosed physical exercises for at least 5 weeks, daily swimming in the pool for at least 20 minutes a day, and Metformin 500 mg 2 times a day and lisinopril 10 mg 1 time per day in the morning.

The inventive method is as follows. After taking 9 ml of blood from the patient in 3.8% sodium citrate in a ratio of 9: 1, it is centrifuged for 5 min at 1000 rpm to obtain BTP. Part of the plasma is taken, and the remaining is centrifuged at 3000 rpm for 20 min, obtaining platelet-poor plasma (BeTP). BTP is standardized according to 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 for each inductor and the studied combination of inductors are selected from the calculation. The remaining plasma volume can be used for other hematological and biochemical studies.

From a selected volume of standardized plasma, 0.02 ml of plasma and two or three inductors solutions (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 at 0.01 ml, three at 0.007 ml.

As agonists it is possible to use ADP, collagen, thrombin, adrenaline in a combination of ADP + adrenaline, ADP + collagen, adrenaline + collagen, ADP + adrenaline + collagen, ADP + adrenaline + thrombin, the required doses of which in this case were lower than with isolated their use, and with any triple combination of inductors even lower. The doses of inducers necessary for aggregation in patients with AH and NTG, 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 people. 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 patients with hypertension and NTG, and especially two and three inducers, a much lower concentration of agonists is required for the development of aggregation, which is probably due to the involvement of several activation mechanisms. It should be noted that the study of the aggregation ability of blood plates with two and three inductors models the events that occur in the bloodstream in the area of vascular damage and the initiation of hemostasis. So, in patients with hypertension and NTG, 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 Standard doses of inducers that cause platelet aggregation when used alone. Inductors ADP, M Adrenaline, M Collagen dilution of the main suspension Thrombin, units / ml Doses 0.5 · 10 ^-4 5 · 10 ^-6 1: 2 0.125

table 2 Minimum mutually potentiating concentrations of aggregation inducers in healthy individuals and patients with arterial hypertension with impaired glucose tolerance with a double and triple combination thereof. Combinations of Platelet Aggregation Inducers Examined Category ADP, M Adrenaline, M Collagen dilution of the main suspension Thrombin, units / ml With one agonist with two agonists with one agonist with two agonists with one agonist with two agonists with one agonist with two agony
stami Healthy people, n = 21 10 ^-6 5 · 10 ^-7 2.5 · 10 ^-7 10 ^-7 1: 4 1: 5 0,100 0,090 Sick people, n = 107 10 ^-7 5 · 10 ^-8 5.0 · 10 ^-8 5-10 ^-8 1: 7 1: 8 0,080 0,070

From tables 1 and 2 it follows that the minimum aggregation-inducing doses of inducers with their combined use are significantly lower than under standard conditions when using the effect on platelets of one agonist. With the simultaneous presence of three inducers in BTP, the doses required for aggregation are even lower than in the case of two inductors. Moreover, in patients with arterial hypertension with impaired glucose tolerance, these values are even lower, which indicates platelet activation expressed in them. The simultaneous use of several inductors brings us closer to the idea of the necessary minimum concentration of inductors in real conditions during the initiation of hemostasis in human vessels.

It is possible to diagnose hypersensitivity to aggregation inducers in patients with hypertension with NTG with the development of platelet aggregation using isolated inducers at doses lower than those indicated in Table 1, and when they are double and triple in combination below those listed in Table 2 for healthy people. In patients with hypertension with NTG, typical concentrations are given in table 2.

When detecting increased sensitivity of platelets to aggregation inducers, hypertensive patients with NTG are prescribed dosed physical activity for 5 weeks, daily swimming in the pool for at least 20 minutes a day and metformin 500 mg 2 times a day and lisinopril 10 mg 1 time per day in the morning.

The inventive method is as follows.

The first component of the proposed method is feasible regular physical training. A possible variant of physical activity is given below.

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 aired. indoors. 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 hypertension with NTG are recommended therapeutic and prophylactic 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 prophylactic gymnastics for persons suffering from hypertension with NTG.

2.1. A lightweight version of therapeutic gymnastics.

Exercise 1. Standing. Walking is calm with a gradual acceleration and deceleration of 1-2 minutes. When performing 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 exhale, 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 inclinations 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 the son-in-law to a lying 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 classes, the use of the following set of exercises is possible.

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 upwards 12-16 times. When bending, exhale, while 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 pelvis turning 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 the 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. Reducing the total load 1-2 minutes

3. Fractional exercise throughout the day.

A patient with hypertension with NTG is a patient with disorders of 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 individuals suffering from hypertension with NTG should be carried out by distributing physical activity in small doses throughout the day. This method of increasing the physical activity of hypertensive patients with NTG should be considered as a fractional load method.

Depending on the real life conditions of hypertensive patients with NTG, various exemplary options for fractional 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.).

The second component of the proposed method is daily swimming in the pool for at least 20 minutes a day, the third is the administration of metformin 500 mg 2 times a day, the fourth component is lisinopril 10 mg 1 time per day in the morning

The method allows to normalize the sensitivity of platelets to aggregation inducers in patients with hypertension with NTG within 5 weeks of treatment, translating it to a level characteristic of healthy individuals. Subject to the following recommendations to the patient, it is possible to exclude the increased sensitivity of platelets of individuals with hypertension and NTG to aggregation inducers, which will significantly reduce their risk of thrombotic complications - strokes and heart attacks.

Example. Patient A., 42 years old, with arterial hypertension and impaired glucose tolerance, registered in the clinic for arterial hypertension in a community clinic, was examined as planned.

The level of platelet aggregation in a patient was evaluated with combinations of inducers: ADP + adrenaline, ADP + collagen, adrenaline + collagen, ADP + collagen + adrenaline, ADP + adrenaline + thrombin. The minimum mutually potentiating aggregation concentration in the case of two inducers was 10 ^-7 M for ADP, 1: 7 for collagen dilution of the main suspension of collagen, adrenaline - 5.0 · 10 ^-8 M, thrombin - 0.080 units / ml. In the case of the simultaneous use of three inductors, their minimum concentration was lower. For ADP - 5.0 · 10 ^-8 M, for collagen - 1: 8 dilution of the main suspension, adrenaline - 5.0 · 10 ^-8 M, thrombin - 0.070 u / ml.

The development of platelet aggregation with such minimal mutually potentiating doses of inducers indicates a violation (activation) of platelet aggregation function.

The patient was prescribed adequate antihypertensive therapy with lisinopril 10 mg once a day, dosed physical activity, daily swimming in the pool for at least 20 minutes a day and metformin 500 mg 2 times a day. This allowed after 5 weeks of treatment to bring the minimum mutually potentiated doses of inducers that cause platelet activation to the level of healthy people. The minimum mutually potentiating aggregation concentration in the case of two inducers was 10 ^-6 M for ADP, 1: 4 dilution of collagen for the main collagen suspension, adrenaline 2.5 · 10 ^-7 M, thrombin 0.100 u / ml. In the case of the simultaneous use of three inductors, their minimum concentration was lower. For ADP -5 · 10 ^-7 M, for collagen - 1: 5 dilutions of the main suspension, adrenaline - 10 ^-7 M, thrombin - 0.090 u / ml.

Thus, platelet activation in response only to mutually potentiating doses of inducers characteristic of healthy people indicates normal platelet function in the examined.

The patient was recommended to continue to comply with her recommendations.

Claims (1)

A method for quickly optimizing the sensitivity of platelets to aggregation inducers in patients with arterial hypertension with impaired glucose tolerance, including the administration of dosed physical activity for at least 5 weeks, daily swimming in the pool for at least 20 minutes per day, administration of lisinopril 10 mg once a day in the morning and metformin 500 mg 2 times a day.

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