RU2726076C1 - Method for pharmacological correction of experimental critical skeletal muscle ischemia with simvastatin - Google Patents

Abstract

FIELD: medicine.SUBSTANCE: invention refers to medicine, particularly to experimental pharmacology and surgery, and can be used to model critical skeletal muscle ischemia. A method for pharmacological correction of experimental skeletal muscle ischemia with simvastatin involves experimental modeling of critical ischemia of the shin muscles, where simvastatin is administered intragastrically in dose of 1.71 mg/kg once a day, daily for 28 days.EFFECT: invention provides developing a method for pharmacological correction of critical shin muscles ischemia by simvastatin in experimental animals.1 cl, 1 ex, 1 tbl

Description

The invention relates to medicine, in particular to experimental pharmacology and surgery, can be used to correct skeletal muscle ischemia.

Closest to the claimed solution is a method for the correction of limb ischemia using trental (pentoxifylline), a drug that improves microcirculation, described Savelyev B.C., Koshkin V.M. "Critical lower limb ischemia." Chapter 7. Treatment of patients with chronic obliterating diseases of the arteries of the lower extremities. Moscow, 1997. The Publishing House "Medicine", which consists in the intra-arterial, intravenous, intramuscular and oral administration of these drugs in patients to correct peripheral circulation disorders.

The main disadvantage of this method is the limited pathogenetic orientation associated with the absence of an endothelium-dependent vasodilating effect while taking trental. The basis of the mechanism of action of trental is a decrease in blood viscosity and an increase in the elasticity of red blood cells, an improvement in microcirculation, and an increase in oxygen concentration in tissues. The increase in erythrocyte elasticity is apparently due to the inhibition of phosphodiesterase and the resulting increase in cAMP content in red blood cells. A decrease in blood viscosity may be due to a decrease in plasma fibrinogen concentration and inhibition of aggregation of red blood cells and platelets.

While statins act immediately on several links of pathogenesis, at any initial level of cholesterol, statins lead to its decrease, it is important to note the fact that they are characterized not only by lipid-lowering, but also non-lipid (pleiotropic) effects. So, they improve endothelial function, have an antithrombotic effect, reduce the activity of inflammatory processes, inhibit the processes of fibrosis, enhance perfusion and angiogenesis. Thus, the use of simvastatin in critical limb ischemia is quite reasonable.

The technical result of the invention is the development of a method for pharmacological correction of critical ischemia of the leg muscles in experimental animals with simvastatin.

The technical result is achieved by the fact that against the background of modeling critical ischemia of the leg muscles in experimental animals, it is corrected by intragastric administration of simvastatin at a dose of 1.71 mg / kg + 1 time per day for 28 days.

The method is carried out as follows.

The experiments are carried out on white rats of the Wistar line weighing 220-250 g.

Experimental animals were divided into the following groups:

1) intact (n = 30);

2) false-operated animals (skin incision along the thigh along the inner surface with the release of the neurovascular bundle of the thigh and suturing of the wound with a continuous suture) (n = 30);

3) modeling of critical ischemia of the leg muscles (removal of the femoral, popliteal, anterior and posterior tibial arteries and veins, as well as the sciatic nerve) (n = 30);

4) modeling of critical ischemia of the leg muscles and its correction with simvastatin (n = 30).

The critical ischemia of the muscles of the left tibia was simulated under anesthesia (chloral hydrate intraperitoneally 300 mg / kg of weight), by operative removal of a section of the great vessels, including the femoral, popliteal, anterior and posterior tibial arteries and veins, as well as the sciatic nerve.

Correction of critical limb muscle ischemia was performed with simvastatin at a dose of 1.71 mg / kg, intragastrically 1 time per day daily for 28 days.

The level of microcirculation in the calf muscles was determined using Biopac systems equipment: MP100 polygraph with laser Doppler flow meter LDF100C and invasive needle probe TSD144 on days 10, 21, and 28. The registration and processing of laser Doppler flowmetry (LDF) results was performed using the AcqKnowledge software version 3.8.1., Microcirculation values were expressed in perfusion units (PE). The microcirculation level curve was recorded at five points (the middle of the muscle length, points 3-5 mm above and below, lateral and medial of the first) for 30 seconds at each point. From the five values obtained, the average was deduced, which was entered into the protocol and was taken as the level of microcirculation in the calf muscles in this animal. From the 10 obtained values, the average was calculated, which was taken as the level of microcirculation in this group of animals at a given time of the study. Registration of the level of microcirculation is carried out in all experimental groups.

In the statistical processing of data, the average value, the standard deviation value, is calculated. Differences are considered significant at p <0.05.

EXAMPLE OF SPECIFIC PERFORMANCE

The results of assessing the level of microcirculation in animals of the experimental groups are presented in table 1.

Table 1

The results of the assessment of the level of microcirculation in the muscles of the tibia of animals of the experimental groups (M ± m) in perfusion units 10 days (n = 10) 21 days (n = 10) 28 days (n = 10) Intact 528.6 ± 11.04 531.6 ± 12.08 533.4 ± 11 False-operated animals 521.4 ± 11.46 523 ± 13.79 524.1 ± 15.1 Modeling critical shin muscle ischemia 160.5 ± 3.28 * 249.1 ± 7.31 * 302.9 ± 6.46 * Simulation of critical ischemia of the leg muscles and its correction with simvastatin 233.6 ± 7.5 ** 382.6 ± 4.33 ** 468.5 ± 6.75 ** Note: * - p <0.05 in comparison with the intact group of animals; ** - p <0.05 compared with a group of animals with critical ischemia of the tibia muscle

The average microcirculation level in the intact muscle of the tibia of rats was 531 ± 12 PE (perfusion units).

In the group of false-operated animals, the average value of the level of microcirculation in the muscles of the left tibia at all periods does not significantly differ from the indicators in the group of intact animals (523 ± 13 PE). In the group of modeling critical ischemia of the leg muscles, the level of microcirculation at all periods led to a significant decrease in the level of regional blood flow in the ischemic muscle of the leg drumstick of rats (10th day p <0.05, 21st day p <0.05; 28th day p <0.05).

Correction with simvastatin contributed to a significant increase in the level of regional blood flow in the ischemic muscle of the tibia of rats compared with the indices of the group of animals with critical ischemia of the tibia muscle at the corresponding time (10th day p <0.05, 21st day p <0.05; 28- e day p <0.05). The level of microcirculation in this group on day 28 is approaching that in the group of intact animals.

Thus, the results obtained allow us to state the pharmacological correction of skeletal muscle ischemia with simvastatin due to the stimulation of neoangiogenesis.

Claims (1)

A method for pharmacological correction of experimental skeletal muscle ischemia with simvastatin, including experimental modeling of critical ischemia of the leg muscles, where simvastatin is administered intragastrically at a dose of 1.71 mg / kg once a day, daily for 28 days.