Combination therapy for chronic limb ischemia

FIELD: medicine.

SUBSTANCE: combination therapy for chronic limb ischemia is ensured by revascularisation osteomyoplasty performed on the laboratory animal with experimental limb on 7th day after modelling. It is followed with intraperitoneal introduction of L-arginine once a day assuring effective circulation management.

EFFECT: higher clinical effectiveness.

1 ex, 1 tbl


The invention relates to medicine, in particular for experimental surgery and pharmacology.

Closest to the claimed solution is a method of correction of limb ischemia using daily single injection of L-arginine at a dose of from 30 to 200 mg/kg proposed Mavrovski et al. (U.S. Pat. No. 2302239 on 10/07/2007,).

The disadvantage of the described method of treatment of ischemia is that monotherapy with L-arginine affects only one pathogenetic link, while the cascade of biochemical changes in the tissues and the complexity of the pathogenetic mechanisms in ischemia require different methods of treatment.

Promising method combined correction of limb ischemia involving the operation revascularise osteomyelitis, which provides for infiltration of muscle stem cells and angiogenic factors in bone marrow, as well as the introduction of L-arginine in the highest dose of 200 mg/kg, which leads to release of nitric oxide and achievement endotheliumderived, vasodilating and Pro-angiogenic effects.

The technical result of the invention is a method of correction of limb ischemia, including the operation revascularizable osteomyelitic followed by the introduction of L-arginine.

Technical result is achieved by the eat, that on the 7th day after modeling ischemia of extremities operation is performed revascularizable osteomyelitis in the Shin, and then daily intraperitoneally once a day injected L-arginine at a dose of 200 mg/kg, which is indispensible NO donor and regulates tissue perfusion due to endothelium-dependent vazodilatiruyuschego effect.

The METHOD IS AS follows

Experiments carried out on white rats-female line "Wistar", Mature, medium weighing 230-260 g

Modeling of limb ischemia was performed under anesthesia (teminal sodium 35 mg/kg) by deleting the section of the main vessel, including the femoral artery, popliteal artery and primary departments crural artery. Assessment of the microcirculation in the calf muscles of the animal is done using a laser-Doppler flowmeter Biopac systems MP-100 and sensor TSD-144 (USA). For this purpose under General anesthesia (teminal sodium 35 mg/kg) was dissected area of the skin in the anterolateral area of the leg. The entry level of the microcirculation was carried out in five points (middle of the length of the muscle, the point at 3-5 mm above and below, the lateral and the more medially first). Check the level of the microcirculation was performed in groups with a simulated ischemia of the extremities and in groups in the treatment of ischemia of the limb L-arginine, using revascularizable osteomyelitis, as well as the combined metodos attraction operations revascularizable osteomyelitic and the subsequent introduction of L-arginine at a dose of 200 mg/kg The results were considered at 10, 21 and 28 days of observation.

When the statistical processing of the data was calculated the mean value, the error of the mean, standard deviation, significance of differences between groups using t-test. The differences were considered significant at p<0,05.


The level of the microcirculation in the right and left leg muscles intact animals did not differ from each other and averaged 533,2+9,7 P.E. (perfusion units). The results of the evaluation of the microcirculation level in animals with a simulated ischemia of the hind limb and in the groups receiving the treatment are presented in table (table 1).

Table 1.
The level of the microcirculation in the control group and the groups receiving the treatment (Mm in absolute values, n=10)
Group10 days21 days28 days
Chronic limb ischemia (control)209,26,4312,113,9to 369.614,6
Chronic limb ischemia+L-arginine 200 mg/kg 239,511,6*415,419,7*489,418,5*
Chronic limb ischemia+surgery revascularizable osteomyelitic249,169,84*439,2124,18*567,1628,12*
Chronic limb ischemia+surgery revascularizable osteomyelitic+L-arginine 200 mg/kg267,017,29*491,2318,47*x622,8421,12*Hu
* - statistical significant differences compared to control at p<0,05.
xstatistical significant differences compared with the group treated with L-arginine 200 mg/kg at p<0,05.
y- statistically significant differences compared with the group who received surgical treatment at p<0,05.

The table shows that the level of microcirculation after surgery simulation ischemic hind limb falls sharply (with 533,2 P.E. to 209,2 P.E.; p<0,001), and then slowly recovers. At 28 days the level of microcirculation in the control remains significantly lower values, which is registered in the group of intact animals (to 369.6 P.E. against 533,2 P.E.; p<0,001).

The treatment differences between experimental and control groups singing who are already at 10 days: in groups, treated with L-arginine at a dose of 200 mg/kg, surgical and combined treatment of the microcirculation level significantly higher than that in the controls (p<0,05).

A similar picture is observed on the 21st day of the experiment, where the experimental groups are statistically significant differences compared with control at p<0,05.

The maximum differences between experimental groups and control took place at 28 days. Here are recorded the best indicators of the level of microcirculation and a statistically significant difference compared with control at p<0,05. It should be noted that the level of microcirculation in all groups treated did not differ significantly from those in the group of intact animals, suggesting that complete restoration of blood circulation in the limb under the influence of treatment.

The best results are marked in the group of animals treated with the combined treatment, where there are significant differences compared to control at all stages of the experiment, as well as significant differences compared with the group treated with L-arginine at a dose of 200 mg/kg

Thus, the combined operation revascularizable osteomyelitic and L-arginine at a dose of 200 mg/kg has advantages over monotherapy with L-arginine. This allows us to recommend this combination to use and like the most is ERSPECTIVE.

The method of combined treatment of chronic limb ischemia, characterized in that laboratory animal with experimental limb ischemia at 7 days after modeling the ischemic limb to perform surgery revascularizable osteomyelitic and then injected intraperitoneally with L-arginine once a day from 7th to 28th day dose up to 200 mg/kg


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