Influence of autologous bone marrow fraction and simvastatin on microcirculation of leg muscles in experimental critical ischemia of the lower limbs

Abstract

Introduction. The effectiveness of cell therapy at the stage of critical limb ischemia is insufficient for regression of clinical manifestations of the ischemic process. Aim – to develop an experimental model of critical limb ischemia and to study the effect of the combined use of bone marrow autocells and simvastatin on the perfusion of ischemic tissues and the dynamics of the clinical picture of the ischemic process. Materials and methods. The experimental study was carried out on 180 male Wistar rats, divided into 6 groups of 30 animals each. In the first group (intact), the level of microcirculation in the muscles of the hind limb was determined. In the second group (sham-operated), the neurovascular bundle of the thigh was isolated and the wound was sutured with a continuous suture. In the third group, chronic critical ischemia of the leg muscles was modeled by removing the femoral, popliteal, anterior and posterior tibial arteries and veins, and damage to the peripheral nerve. In the fourth group, critical ischemia of the leg muscles was treated with simvastatin, in the fifth group – with the mononuclear fraction of autologous bone marrow, in the sixth one – with simvastatin and the mononuclear fraction of autologous bone marrow. The level of microcirculation in the leg muscles was determined using laser Doppler flowmetry LDF 100C and invasive needle sensor TSD144 on days 10, 21 and 28. Results. In the second group, a statistically insignificant decrease in the level of microcirculation was noted. In the third group, the level of regional blood flow in the ischemic muscle of the leg of rats on the 10th day was 2.5 times, on the 21st day – 1.7 times and on the 28th day 1.4 times less than in the group of intact animals. At the same time, in the fourth group after the administration of simvastatin to the animals, the regional blood flow increased 1.4; 1.5 and 1.5 times; in the fifth group, with the introduction of the mononuclear fraction of the bone marrow to animals at all periods, 1.6 times; in the sixth group after the combined administration of bone marrow cells and simvastatin – 2.0; 1.8 and 1.7 times. By the end of the experiment, in the animals of the fourth and fifth groups, it was possible to stop the progression of clinical manifestations, and in animals of the sixth group, their regression was achieved. Conclusion. The combined use of bone marrow cells and statins allows bringing the level of perfusion of ischemic tissues to normal and achieving regression of the clinical picture of the ischemic process by the end of the experiment.