Rational Pharmacotherapy in Cardiology

Advanced search


Full Text:


The review is devoted to the modern data about mechanisms of cardiovascular dysfunction in patients suffering diabetes mellitus type 2, especially to the role of oxidative stress. It is determined that oxidative stress is involved in the development of myocardial ischemia, reperfusion-syndrome, en￾dothelial dysfunction and atherogenesis. There are data that angiotensin converting enzyme inhibitor, zofenopril, has both cardio- and vasoprotective activities as well as antioxidative effect. These features are rationales to use it in patients with ischemic heart disease and diabetes mellitus.

About the Authors

K. S. Lexina
Moscow State medico-stomatological University
Russian Federation
Chair of therapy and family medicine

N. Y. Timofeeva
Moscow State medico-stomatological University
Russian Federation
Chair of therapy and family medicine

V. S. Zadionchenko
Moscow State medico-stomatological University
Russian Federation
Chair of therapy and family medicine

G. G. Shehian
Moscow State medico-stomatological University
Russian Federation
Chair of therapy and family medicine

K. A. Aldushina
Moscow State medico-stomatological University
Russian Federation
Chair of therapy and family medicine


1. Профилактика неинфекционных болезней: опыт и перспективы. Под ред. Е. Лепарского. ВОЗ, Женева, 1991.

2. Задионченко В.С., Яковлева М.С., Шехян Г.Г., Миронова М.А. Применение карведилола в комплексной терапии больных инфарктом миокарда с зубцом Q. Тер арх 2005;477(8):14-9.

3. Haffner S.M., Lehto S., Ronnemaa T., et al. Mortality from coronary heart disease in subjects with type 2 diabetes and nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 1998;339:229-34.

4. Melchior T, Kober L, Madsen CR, et al. Accelerating impact of diabetes mellitus on mortality in the years following an acute myocardial infarction. TRACE Study Group. Trandolapril Cardiac Evaluation. Eur Heart J 2000;21:1937-43.

5. Дедов И.И., Александров А.А. Диабетическое сердце: Causa Magna. Сердце 2004;3(1):5-8.

6. Панченко Е.П. Ишемическая болезнь сердца и сахарный диабет - коварный тандем. Сердце 2004; 3(1): 9-12.

7. Stamler J, Vaccaro O, Neaton J, et al. Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the multiple risk factor intervention trial. Diabetes Care 1993;16:433-44.

8. Clark CM Jr, Perry RC. Type 2 diabetes and macrovascular disease: epidemiology and etiology. Am Heart J 1999;138(5 Pt l ):S330-3.

9. Torp-Pedersen C, Rask-Madsen C, Gustafsson I, et al. Diabetes mellitus and cardiovascular risk: just another risk factor? Eur Heart J Suppl 2003;5:F26-32.

10. Granger CB, Califf RM, Young S. et al. Outcome of patients with diabetes mellitus and acute myocardial infarction treated with thrombolytic agents. The Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) Study Group. J Am Coll Cardiol 1993;21:920-5.

11. Timmis AD. Diabetic heart disease: clinical considerations. Heart 2001;85:463-9.

12. Woodfield SL, Lundergan CF, Reiner JC, et al. Angiographic findings and outcome in diabetic patients treated with trombolytic therapy for acute myocardial infarction: the CUSTO-1 experience. J Am Coll Cardiol 1999;28:1661-9.

13. Mokhtar N., Lavoie J-P., Rousseau-Migneron S., Nadeau A. Physical training reverses defect in myocardial energy production in heart of cronically diabetic rats. Diabetes 1993;42:686-7.

14. Hail JL, Stanley WS, Lopaschuk GD, et al. Impaired pyruvate oxidation but not glucose uptake in diabetic pig heart during dobutamine stress. Am J Physiol 1996;271:H2320-9.

15. Chen V, Ianuzzo D, Fong BC, Spitzer JJ. The effects of acute diabetes on myocardial metabolism in rats. Metabolism 1984;33:1078-84.

16. Chatham JC, Forder JR. A 13C-NMR study of glucose oxidation in the intact functioning rat heart following diabetes-induced cardiomyopathy. J Mol Cell Cardiol. 1993;25(10):1203-13.

17. Wall SR, Lopaschuk GD. Glucose oxidation rates in fatty acid-perfused isolated working hearts from diabetic rats. Biochem Biophys Acta 1989;1006:97-103. 18. Avogaro A, Nosadini R, Doria A, et al. Myocardial metabolism in insulin-deficient diabetic humans without coronary artery disease. Am J Physiol 1990;258:E606-18.

18. Дедов И.И., Александров А.А. Диабетическое сердце: основные закономерности. М.: ЭНЦ РАМН, 2004.

19. Lopaschuk GD. Advantages and limitations of experimental techniques used to measure cardiac energy metabolism. J. Nucl Cardiol 1997;4:316-28.

20. Liepinsh E, Vilskersts R, Loca D, et al. Mildronate, an inhibitor of carnitine biosynthesis, induces an increase in gamma-butyrobetaine contents and cardioprotection in isolated rat heart infarction. J Cardiovasc Pharmacol. 2006;48(6):314-9.

21. Меерсон Ф.З. Патогенез и предупреждение стрессорных и ишемических повреждений сердца. М.: Медицина,1984.

22. Opie LH. Cardiac metabolism-emergence, decline and resurgence. Part 1. Cardiovasc Res 1992;26:721-33.

23. Galderisi M, Anderson KM, Wilson RW, Levy D. Ehocardiographic evidence for existence of a distinct diabetic cardiomyopathy (the Framingham Heart Study). Am J Cardiol 1991;68:85-9.

24. Stone PH, Muller JE, Hartwell T, et al. The effect of diabetes mellitus on prognosis and serial left ventricular function after acute myocardial infarction: contribution of both coronary disease and diastolic left ventricular dysfunction to the adverse prognosis. J Am Coll Cardiol 1989;14:49-57.

25. Cleland SJ, Petrie JR, Small M, et al. Insulin action is associated with endothelial function in hypertension and type 2 diabetes. Hypertension 2000;35:507-11.

26. Taylor A.A. Pathophysiology of hypertension and endothelial dysfunction in patients with diabetes mellitus. Endocrinol Metab Clin N Am 2001;30:983-97.

27. Rask-Madsen C, Ihlemann N, Krarup T, et al. Insulin therapy improves insulin-stimulated endothelial function in patients with type 2 diabetes and ischemic heart disease. Diabetes 2001;50:2611-8.

28. Зенков Н.К., Кандалинцева Н.В., Ланкин В.З., Меньщикова Е.Б., Просенко А.Е. Фенольные биоантиоксиданты. Новосибирск: Издательство СО РАМН, 2003.

29. Зенков Н.К., Ланкин В.З., Меньщикова Е.Б. Окислительный стресс. Биохимический и патофизиологические аспекты. Москва: МАИК «Наука/Интерпериодика», 2001.

30. Ланкин В.З., Тихазе А.К., Беленков Ю.Н. Антиоксиданты в комплексной терапии атеросклероза: PRO ET CONTRA (Пособие для врачей). Москва: РКНПК МЗ РФ, 2006.

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

32. Ланкин В.З., Тихазе А.К., Беленков Ю.Н. Свободнорадикальные процессы в норме и при патологических состояниях (Пособие для врачей). М.: РКНПК МЗ РФ, 2001.

33. Климов А.Н., Никульчева Н.Г. Обмен липидов и липопротеидов и его нарушения. СПб.: Питер, 1999.

34. Lankin VZ, Tikhaze AK, Osis YG. Modeling the cascade of enzymatic reactions in liposomes including successive free radical peroxidation, reduction, and hydrolysis of phospholipid polyenoic acyls for studying the effect of these processes on the structural-dynamic parameters of the membranes. Biochemistry (Mosc) 2002;67(5):566-74.

35. Esterbauer H, Gebicki J, Puhl H, Jurgens G. The role lipid peroxidation and antioxidants in oxidative modification of LDL. Free Radic Biol Med 1992;13(4):341-90.

36. Witztum J.L., Steinberg D. Role oxidized low-density lipoprotein in atherogenesis. J Clin Invest 1991;88(6):1785-92.

37. Maggioni AP. ACE inhibitor treatment after myocardial infarction. Eur Heart J 1999;Suppl Q:7-10.

38. Hall AD, Murray GD, Ball SG. Follow-up study of patients randomly allocated ramipril or placebo for heart failure after acute myocardial infarction: AIRE Extension (AIREX) Study. Acute Infarction Ramipril Efficacy. Lancet 1997;349:1493-7.

39. Scribner AW, Loscalzo J, Napoli C. The effect of angiotensin converting enzyme inhibition on endothelial function and oxidant stress. Eur J Pharmacol 2003;482(1-3):95-9.

40. Pepine CJ, Celermajer DS, Drexler H. Vascular health as a therapeutic tagert in cardiovascular disease. University of Florida, 1998.

41. Keidar S, Kaplan M, Hoffman A, et al. Angiotensin II stimulates macrophage-mediated lipid peroxidation of LDL. Atherosclerosis 1995;115:201-15.

42. Scholkens BA, Landgraf W. ACE inhibition and atherogenesis. Can J Physiol Pharmacol. 2002;80(4):354-9.

43. McFarlane SI, Kumar A, Sowers JR. Mechanisms by which angiotensin-converting enzyme inhibitors prevent diabetes and cardiovascu￾lar disease. Am J Cardiol. 2003;91(12A):30H-37H.

44. Opie LH, Schall R. Old antihypertensives and new diabetes. J Hypertens 2004;22:1453-8.

45. Cominacini L, Pasini A, Garbin U, et al. Zofenopril inhibits the expression of adhesion molecules on endothelial cells by reducing reactive oxygen species. Am J Hypertens 2002;15(10 Pt 1):891-5.

46. Subissi A, Evangelista S, Giachetti A. Preclinical profile of zofenopril: an angiotensin converting enzyme inhibitor with peculiar cardioprotective properties. Cardiovasc Drug Rev 1999;17(2):115-33.

47. de Nigris F, D'Armiento FP, Somma P, et al. Chronic treatment with sulfhydryl angiotensin-converting enzyme inhibitors reduces susceptibility of plasma LDL to “in vitro” oxidation, formation of oxidationspecific epitopes in the arterial wall, and atherogenesis in apolipoprotein E knockout mice. Int J Cardiol 2001;81(2-3):107- 15.

48. Buikema H, Monnink SH, Tio RA, et al.: Comparison of zofenopril and lisinopril to study the role of the sulfhydryl-group in improvement of endothelial dysfunction with ACE-inhibitors in experimental heart failure. Br J Pharmacol. 2000;130(8):1999-2007.

49. Ambrosioni E., Borghi C., Magnani B. The effect of the angiotensinconverting-enzyme inhibitor zofenopril on mortality and morbidity after anterior myocardial infarction. The Survival of Myocardial Infarction Long-Term Evaluation (SMILE) Study Investigators. N Engl J Med 1995;332:80-5.

50. Borghi C, Ambrosioni E; Survival of Myocardial Infarction Long-term Evaluation-2 Working Party. Double-blind comparison between zofenopril and lisinopril in patients with acute myocardial infarction: results of the Survival of Myocardial Infarction Long-term Evaluation-2 (SMILE-2) study. Am Heart J 2003;145:80-7.

51. Borghi C, Ambrosioni E; Survival of Myocardial Infarction Long-term Evaluation Study Group. Effects of zofenopril on myocardial ischemia in post-myocardial infarction patients with preserved left ventricular function: the Survival of Myocardial Infarction Long-term Evaluation (SMILE)-ISCHEMIA study. Am Heart J. 2007;153(3):445.e7-14.

52. Borghi C, Bacchelli S, Esposti DD, et al. Effects of the early ACE inhibition in diabetic nonthrombolyzed patients with anterior acute myocardial infarction. Diabetes Care. 2003;26(6):1862-8.

For citation:


Views: 398

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

ISSN 1819-6446 (Print)
ISSN 2225-3653 (Online)