EFFECTS OF Β-ADRENOBLOCKERS ON MYOCARDIAL REMODELING, IMMUNO-INFLAMMATORY REACTIONS AND ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH ISCHEMIC HEART DISEASE AND CHRONIC HEART FAILURE

Aim. To assess the effect of β-adrenoblockers (BAB) on myocardial remodeling, immuno-inflammatory reactions and endothelial dysfunction in patients with ischemic heart disease and chronic heart failure (CHF).

Material and methods. 84 patients with ischemic CHF of II-IV functional class were involved in the study. They were randomized in two groups. The first group was presented with 43 patients receiving carvedilol in addition to standard therapy for 24 weeks; the second group was presented with 41

patients receiving metoprolol. Echocardiography, 6-minute walk test were applied. Blood levels of primary and secondary lipid peroxidation (LP) products, cytokines, endothelin-1 (ET-1), intercellular adhesive molecule (VCAM-1) were determined.

Results. Both of BAB improved the clinical condition and physical working ability of patients with CHF. Carvedilol in comparison with metoprolol was more effective in myocardial remodeling prevention, inhibition of pro-inflammatory cytokines [tumor necrosis factor alpha (TNF-α), interleukins (IL-1β IL-6)] and LP. Besides carvedilol increased in endothelium-dependent vasodilatation and reduced in ET-1 and VCAM-1 levels.

Conclusion. Long-term carvedilol treatment has anti-inflammatory, antioxidant and endothelium-protective effects as well as improves haemodynamics. 

1. Беленков Ю.Н. ИБС как основная причина сердечной недостаточности. Сердечная недостаточность 2004;5(2):77-8.

2. Adams K.F.Jr, Dunlap S.Н., Sueta C.A. et al. Relation between gender, etiology and survival in patients with symptomatic heart failure. J Am Coll Cardiol 1996;28(7):1781-8.

3. Cleland J.G., Khand A., Clark A. The heart failure epidemic: exactly how big is it? Eur Heart J. 2001;22(8):623-6.

4. Ferrari R, Ceconi C, Curello S, Visioli O. The neuroendocrine and sympathetic nervous system in congestive heart failure. Eur Heart J. 1998;19 Suppl F:F45-51.

5. Patten RD, Udelson JE, Konstam MA. Ventricular remodeling and its prevention in the treatment of heart failure. Curr Opin Cardiol 1998;13(3):162-7.

6. Communal C., Singh K., Pimentel D.R., Colucci W.S. Noreperinephrine stimulates apoptosis in adult rat ventricular myocytes by activation of the beta-adrenergic pathways. Circulation 1988;98(13):1329-34.

7. Mann D.L., Young J.B. Basic mechanisms in congestive heart failure. Recognizing the role of proinflammatory cytokines. Chest 1999;105(3):897-904.

8. Ланкин В.З., Тихазе А.К., Беленков Ю.Н. Свободнорадикальные процессы при заболеваниях сердечно-сосудистой системы. Кардиология 2000;40(7):48-61.

9. Oskarsson H.J., Heistad D.D. Oxidation stress produced by angiotensin too. Implications for hypertension and vascular injury. Circulation 1997;95(3):557-9.

10. Torre-Amione G., Karadia S., Lee J. et al. Expression and functional significance of tumor necrosis factor receptors in human myocardium. Circulation 1995;92(6):1487-93.

11. Kaul N., Siveski-Iliskovic N., Hill M. et al. Free radicals and the heart. J Pharmacol Toxicol Methods 1993;30(2):55-67.

12. Harrison D.G. Endothelial function and oxidant stress. Clin Cardiol 1997;20(11 Suppl 2):II-11-7.

13. Насонов Е.Л., Самсонов М.Ю., Беленков Ю.Н., Фукс Д.А. Иммунопатология застойной сердечной недостаточности: роль цитокинов. Кардиология 1999;39(3):66-73.

14. Васюк Ю.А., Дударенко О.П., Ющук Е.Н. и др. «Цитокиновая» модель патогенеза хронической сердечной недостаточности и возможности нового терапевтического подхода к лечению декомпенсированных больных. Рациональная фармакотерапия в кардиологии 2006;(4):63-70.

15. Cannon R.O. Role of nitric oxide in cardiovascular disease: focus on the endothelium. Clin Chem 1998;44:1809-19.

16. Packer M., Coats A. J., Fowler M.B. et al. Effect of carvedilol on survival in severe heart failure. N Eng J Med 2001;344(22):1651-8.

17. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial. Lancet 2001;357:1385-90.

18. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 1999;353:2001-7.

19. Poole-Wilson P.A., Swedberg K., Cleland J.G. et al. Comparison of carvedilol and metoprolol in clinical outcomes in patients with chronic heart failure. Carvedilol or Metoprolol European Trial (COMET) randomized controllied trial. Lanced 2003;362:7-13.

20. Васюк Ю.А., Козина А.А., Ющук Е.Н. и др. Особенности диастолической функции и ремоделирования левого желудочка у больных артериальной гипертензией и ишемической болезнью сердца. Сердечная недостаточность 2003;4(4):190-2.

21. Bolland J.L., Koch H.P. The course of an oxidation reaction in polyisoprenes and allied compounds. IX. The primary thermal oxidation products of ethyl linoleate. J Chem Soc 1945;112:444-5.

22. Bidlack W.R., Tappel A.L. Fluorescent products of phospholipids during lipid peroxidation. Lipids 1973;8(4):203-7.

23. Coletta A.P., Louis A.A., Clark A.L. et al. Clinical trials update from the European Society of Cardiology: CARMEN, EARTH, OPTIMAAL, ACE, TEN-HMS, MAGIC, SOLVD-X and PATH-CHF II. Eur J Heart Fail 2002;4(5):661-6.

24. Packer M., Antonopoulos G.V., Berlin J.A. et al. Comparative effects of carvedilol and metoprolol on left ventricular ejection fraction in heart failure: results of a meta-analysis. Am Heart J. 2001;141(6):899- 907.

25. Yaoita H., Sakabe A., Maehara K., Maruyama Y. Different effects of carvedilol, metoprolol and propranolol on left ventricular remodeling after coronary stenosis or after permanent coronary occlusion in rats. Circulation 2002;105:975-980.

26. Закирова А.Н., Мухаметрахимова А.Р., Закирова Н.Э. Состояние систолической функции левого желудочка и активность провоспалительных цитокинов при остром инфаркте миокарда. Сердечная недостаточность 2005;6(4):14-6.

27. Тепляков А.Т., Дибиров М.М., Болотская Л.А. и др. Модулирующее влияние карведилола на активацию цитокинов и регресс сердечной недостаточности у больных с постинфарктной дисфункцией сердца. Кардиология 2004;44(9):50-7.

28. Ferrari R., Agnoletti L., Comini L. et al. Oxidative stress during myocardial ischemia and heart failure. Eur Heart J 1998;19 Suppl B:B2- 11.

29. Dandona P., Karne R., Chanim H. et al. Carvedilol inhibits reactive oxygen species generation by leukocytes and oxidative damage to amino acids. Circulation 2000;101(2):122-4.

30. Алмазов В.А., Ситникова М.Ю., Иванов С.Г. и др. Карведилол в лечении больных хронической сердечной недостаточностью: клинические и метаболические эффекты. Сердечная недостаточность 2001;2(2):68-70.

31. Ситникова М.Ю., Хмельницкая К.А., Иванов С.Г. и др. Влияние терапии метопрололом – CR/XL на состояние эндотелия, некоторые показатели атеросклероза и системы гемостаза у пациентов хронической сердечной недостаточностью ишемической этиологии. Сердечная недостаточность 2002;4(14):169-71.