Effect of drug therapy for chronic obliterating diseases of lower-limb arteries on the state of the microcirculatory bed

Uchkin I.G.^1,2, Zudin A.M.^1,2, Bagdasaryan A.G.², Fedorovich A.A.^3,4

1) Chair of Hospital Surgery, Medical Department, Russian University of Friendship of Peoples,
2) Department of Vascular Surgery No2, N.A. Semashko Central Clinical Hospital No2, Open Joint-Stock Company "Russian Railways",
3) Department of New Diagnostic Methods, Institute of Clinical Cardiology named after A.L. Myasnikov of the Russian Cardiological Research and Production Complex under the RF Public Health Ministry,
4) Federal Scientific Centre of the Russian Federation Institute of Biomedical Problems under the Russian Academy of Sciences, Moscow, Russia

Search for an optimal method of conservative treatment of patients presenting with chronic obliterating disease of lower limb arteries (CODLLA) still remains an important and hitherto unsolved problem. Comparative studies of different drugs and objective assessment of their efficacy may be carried out using the method of laser Doppler flowmetry (LDF) with wavelet analysis of fluctuations in blood flow.

Objective. The study was aimed at assessing efficacy of using Actovegin in conservative treatment of patients presenting with chronic obliterating disease of the lower extremities induced by occlusive and stenotic lesions of the arterial bed.

Materials and methods. The study included a total of 80 patients with stage 2B chronic ischaemia of the lower limbs. The patients were subdivided into two groups. Group One comprised 40 patients undergoing a course of intravenous infusions of Actovegin (at a dose of 250 ml, 4 mg/ml) as monotherapy for 10 days. Group Two comprised 40 patients receiving intravenous infusion of dextranes, as well as pentoxyphyllin at a dose of 100 mg/day. The state of microcirculation before and after the course of the infusion therapy was assessed by means of LDF with wavelet analysis of blood follow fluctuations. The basal blood flow was registered at a temperature of +32°C for 10 minutes followed by a thermal test, i.e., heating to +42°C for 30-40 minutes.

Results. The course of infusion therapy in Group One patients was followed by an increase of the amplitude of myogenic fluctuation by 56% (p=0.006) and a decrease in the index of blood flow shunting (p=0.1) with basal perfusion, as well as an increase in the maximum level of perfusion (p=0.006). Group Two patients showed were found to have only statistically significant shortening of the time of reaching the maximum level of thermal hyperaemia. The increase of the pain-free walking distance averagely amounted to 58.8% in Group One patients and 60.7% in Group Two (p=0.068). Patients of the both groups showed satisfactory tolerance of the carried out therapy. No undesirable adverse events were observed.

Conclusions. LDF with wavelet analysis of fluctuations of blood flow makes it possible to thoroughly study the mechanisms of action of therapeutic agents on microcirculation in patients with CODLLA. The use of Actovegin as monotherapy in CODLLA patients leads to a decrease in the myogenic tonus of precapillary arterioles and capillary sphincters, to a decrease in the arteriolar-venular shunting of blood flow with predominant supply of blood to the capillary bed, to an increase in the oxide-synthase function of the endothelium of microvessels (endothelioprotective effect), as well as to an increase in the maximum level of thermal vasodilatation. Hence, Actovegin may be considered as a promising therapeutic agent for pharmacotherapy of CODLLA.

KEY WORDS: eripheral artery diseases, pharmacotherapy, Actovegin, microcirculation, laser Doppler flowmetry, wavelet analysis.

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