RU2438192C1 - Ischemia correction method - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: ischemia is simulated on an animal's hind limb. That is ensured by removing a portion of great vessel including a femoral artery, a popliteal artery and initial portions of shin arteries. It is followed by 10-minute cross-clamping of the femoral artery of a contralateral limb and 30-minute reperfusion (distant pre-conditioning).

EFFECT: effective ischemia treatment ensured by stimulated neovasculogenesis.

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Description

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

It was found that tissue resistance to ischemia can increase as a result of preconditioning caused by short episodes of ischemia - reperfusion. (Katagawa et al., 1991, Vlasov T.D. et al. 2004, Sharp F.R. et al., 2004).

Interesting from the point of view of practical use is the phenomenon of distant (remote) preconditioning, the essence of which is that short-term episodes of ischemia of one organ (kidney, mesentery, lower limb) increase the resistance of other organs to severe ischemic damage.

Closest to the claimed solution is a method for correcting limb ischemia with a single daily administration of L-arginine at a dose of 30 to 200 mg / kg, proposed by M.V. Pokrovsky et al., Patent for invention RU 2302239 C1.

However, this solution is possible only with the use of the drug, which entails a number of side effects.

The objective of the invention is to develop a method for the correction of ischemia, excluding the use of drugs.

The task is achieved by the fact that in order to correct ischemia modeled on the hind limb, a laboratory animal undergoes remote preconditioning, carried out by a 10-minute contraction of the femoral artery of the contralateral limb, followed by 30-minute reperfusion.

The method is carried out as follows.

The experiments were carried out on white Wistar female rats weighing 200-220 g. Ischemia was simulated on the hind limb under anesthesia (chloral hydrate 50 mg / kg ip) by removing a section of the main vessel, including the femoral artery, popliteal artery, and the initial parts of the leg artery.

Distant preconditioning is performed by a 10-minute contraction of the femoral artery of the contralateral limb, followed by a 30-minute reperfusion.

Microcirculation in the muscles of the tibia of the animal is assessed using a Biopac-systems MP-100 laser-Doppler flowmeter and TSD-144 sensor (USA). To do this, under anesthesia (chloral hydrate 50 mg / kg of weight intraperitoneally), a section of skin is excised in the anterolateral region of the leg region. The microcirculation level is recorded at five points (the middle of the muscle length, points 3-5 mm above and below, lateral and medial of the first).

The microcirculation level is recorded in the group of animals with ischemia modeled on the hind limb and in the group of animals that underwent correction of hind limb ischemia by distant preconditioning.

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

EXAMPLE OF SPECIFIC PERFORMANCE

The experiments were carried out on white rats male Wistar line weighing 200-220 g

The level of microcirculation in the right and left muscles of the leg of intact animals did not differ from each other and amounted to 533.2 ± 9.7 p.u. (perfusion units).

Experimental animals were divided into the following groups:

1) modeling of ischemia (n = 20);

2) modeling of ischemia + distant preconditioning (n = 20).

Ischemia was modeled on the hind limb under anesthesia (chloral hydrate 50 mg / kg ip) by removing a portion of the main vessel, including the femoral artery, popliteal artery, and the initial parts of the leg arteries. In the second group of animals, distant preconditioning was performed with a 10-minute contraction of the femoral artery of the contralateral limb followed by a 30-minute reperfusion.

Microcirculation in the muscles of the leg of the animal was assessed using a Biopac-systems MP-100 laser-Doppler flowmeter and a TSD-144 sensor (USA) on days 21 and 28. To do this, under anesthesia (chloral hydrate 50 mg / kg ip), a section of skin was excised in the anterolateral region of the leg. The microcirculation level is recorded at five points (the middle of the muscle length, points 3-5 mm above and below, lateral and medial of the first). The microcirculation level curve was recorded 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 10 obtained values, the average was deduced, which was taken as the level of microcirculation in this group of animals at a given time of the study.

The results of assessing the level of microcirculation in animals with modeling of hind limb ischemia and in the group of animals that underwent correction of ischemia modeled on the hind limb by distant preconditioning are presented in the table.

Table 1 The results of assessing the level of microcirculation in the muscles of the leg (M ± m) 21 days (n = 10) 28 days (n + 10) Limb ischemia 322.43 ± 13.9 361.454 ± 11.955 Limb ischemia + distant preconditioning 450.33 ± 27.3 * 712.3 ± 14.575 * * - p <0.05 compared with a group of animals with limb ischemia ** - p <0.05 compared with a group of animals with limb ischemia treated with L-NAME

The table shows that the level of microcirculation after surgery to model ischemia of the hind limb at 21 days 322.43 ± 13.9 p.u., at 28 days - 361.454 ± 11.955 p.u., which is significantly lower than the value in the group of intact animals (p <0.001).

Against the background of correction by distant preconditioning for 21 days, the level of microcirculation significantly increases to 450.33 ± 27.3 p.u. (p <0.05), and by 28 - up to 712.3 ± 14.575 b.p. (p <0.0000000087).

Thus, the results obtained make it possible to ascertain the correction of ischemia by distant preconditioning.

Claims (1)

A method for correcting ischemia, including modeling it on the hind limb of a rat, characterized in that the distant preconditioning is performed on the laboratory animal by 10 minutes of contraction of the femoral artery of the contralateral limb followed by 30 minutes of reperfusion.