Authors
Fejziev E.E.1, Sukovatyh B.S.1, Zatolokina M.A.1, Belous A.S.2, Trubnikova E.V.2
1 Kursk State Medical University, Kursk
2 Research Laboratory «Genetics», Kursk State University, Kursk
Abstract
Aims: To study the effect of simvastatin on trophic changes in skeletal muscles in experimental critical limb ischemia.
Materials and methods: We investigated the effectiveness of pharmacotherapy for this disease with simvastatin (Simvastatin, Pharmstandard-leksredstva, Russia). Calf muscle ischemia was simulated in Wistar rats. Formed 4 groups of animals, 20 individuals: intact; falsely operated; with simulated critical ischemia without treatment (control group); with critical ischemia and simvastatin monotherapy (orally 1.71 mg / kg, daily, once for 28 days, experimental group). The level of blood microcirculation in the leg muscles was measured on the 21st and 28th days. At the same time, 10 animals were withdrawn from the experiment by anesthesia overdose and histological preparations of the leg muscles were prepared.
Results: The level of regional blood flow significantly (p <0.05) increased in the experimental group compared to the control. Macroscopically, the muscles of animals in the experimental groups did not differ from the muscles of intact animals, microscopically, a decrease in the number and size of necrotic areas characteristic of ischemic muscles of rats that did not receive treatment was observed.
Conclusions: The effectiveness of therapy for critical lower limb ischemia, simulated in rats with simvastatin, was shown. The level of blood microcirculation in the affected leg muscles of the animals of the corresponding experimental group on the 28th day was significantly one and a half times higher (in perfusion units) than in the animals of the control group. Morphological study of the leg muscles of rats in the group with the correction of critical ischemia with simvastatin showed a decrease in the number and size of necrotic areas. The study allows us to recommend the use of statins, in particular simvastatin, for the treatment of patients with critical limb ischemia, both in outpatient and inpatient practice.
Keywords: ischemia, lower limbs, correction, simvastatin, rats.
References
1. Katelnickij II, Livadnjaja ES. Methods for the treatment of patients with obliterating atherosclerosis of the arteries of the lower extremities in critical ischemia. Sovremennye problemy nauki i obrazovanija. 2014; (3). (In Russ).
2. Patent RUS 2497203 ot 27.10.2013. Pokrovskij MV, Kolesnik IM, Hodov SV, Pokrovskaja TG, Dolzhikov AA, Efremenkova DA, et al. A method for pharmacological correction of skeletal muscle ischemia with sildenafil, including in I-name-induced nitric oxide deficiency. (In Russ).
3. Kovalenko V, Kalitko I, Temrezov M, et al. Possibilities of treating patients with atherothrombotic lesions of the arteries of the lower extremities. Vrach. 2010; (3): 55–8. (In Russ).
4. Chervjakov JuV, Staroverov IN, Nersesjan EG, et al. Therapeutic angiogenesis in the treatment of patients with chronic obliterating diseases of the arteries of the lower extremities. Blizhajshie i otdalennye rezul’taty. Angiologiya i sosudistaya hirurgiya. 2012; 18(3): 19–27. (In Russ).
5. Walter DH, Krankenberg H, Balzer JO, et al. Intraarterial administration of bone marrow mononuclear cells in patients with critical limb ischemia: a randomized-start, placebo-controlled pilot trial (PROV-ASA). Circ Cardiovasc Interv; 2011 Feb 1; 4(1): 26–37.
6. Fesenko JeV, Proshhaev KI, Poljakov VI. Pleiotropic effects of statin therapy and their role in overcoming the problem of polymorbidity. Sovremennye problemy nauki i obrazovanija. 2012; (2). (In Russ).
7. Arutjunov GP, Bojcov SA, Voevoda MI, et al. Correction of hypertriglyceridemia to reduce the residual risk in diseases caused by atherosclerosis. Zakljuchenie Soveta jekspertov Rossijskogo kardiologicheskogo obshhestva, Rossijskogo nauchnogo medicinskogo obshhestva terapevtov, Evrazijskoj associacii terapevtov, Nacional’nogo obshhestva po izucheniju ateroskleroza, Rossijskoj associacii jendokrinologov i Nacional’noj issledovatel’skoj ligi kardiologicheskoj genetiki. Racional’naja Farmakoterapija v Kardiologii. 2019; 15(2): 282–8. (In Russ).
8. Patent RUS 2734158 ot 18.03.2020. Fejziev Je.Je., Belous A.S., Sukovatyh B.S., Trubnikova E.V. A method for modeling critical ischemia of the lower extremities in experimental rat animals. (In Russ).
9. Kolesnik IM, Lazarenko VA, Pokrovskij MV. Effect of pharmacological preconditioning with sildenafil and vardenafil on the state of the microvasculature in ischemic skeletal muscle. Chelovek i ego zdorov’e. 2015; (1): 83–6. (In Russ).
10. Pokrovskaja TG, Chuljukova TN, Pokrovskij MV, Filippenko NG. Endothelioprotective dose-dependent effects of sildenafil in combination with L-arginine in experimental modeling of L-NAME-induced nitric oxide deficiency. Biomedicina. 2010; 1(5): 118–20. (In Russ).
11. Soloveva AE, Kobalava ZhD. Prospects for anti-inflammatory therapy of atherosclerosis. Klinicheskaja farmakologija i terapija, 2014; 23(3). (In Russ).
