Clinical Physiology of Circulation

Chief Editor

Leo A. Bockeria, MD, PhD, DSc, Professor, Academician of Russian Academy of Sciences, President of Bakoulev National Medical Research Center for Cardiovascular Surgery


Новые данные о механизмах влияния фармакологического лечения на гипертрофию миокарда у пациентов с обструктивной формой гипертрофической кардиомиопатии

E-mail: Сведения доступны для зарегистрированных пользователей.

Link: Clinical Physiology of Blood Circulaiton. 2013; (): -

Full text:  

Abstract

Objective. To study peculiarities of influence of various groups of pharmacologic agents on hypertrophy development at the cellular level in patients with obstructive form of hypertrophic cardiomyopathy.
Material and methods. Our study included 38 patients (mean age 39.339.3±12.6 years) with obstructive form of hypertrophic cardiomyopathy (HTCM) who underwent surgical treatment. Various groups of pharmacologic agents were used in preoperative stage: 34 patients (90%) took beta-adrenergic blocking agents, 4 patients (10%) – calcium channel-blocking agents, 30 patients (79%) – angiotensin-converting enzyme inhibitors and 28 patients (74%) – aldosterone antagonists. Myocardial biopsy was obtained from interventricular septum during myectomy. Proliferative capacity of myocardium was evaluated with immunoconfocal microscopy for the expression in cardiomyocytes (CM) of proliferation marker (Ki67) along with cardiogenic cell differentiation marker (alpha sarcomeric actin). Cardiomyocytes stem cells precursors were defined according to stem cells marker expression (c-kit) in combination with cardiomyogenic cell differentiation marker (alphasarcomeric actin). Myocardial fibrosis and cardiomyocyte hypertrophy intensity was evaluated with light microscopy.
Results. There are proliferative active cardiomyocytes of various maturity (large Ki67+/±-sarc+ 128/106 CМ and small Ki67+/±-sarc+ 190/106 CМ) as well as cardiac resident stem cells (c-kit+/ ±-sarc+ 50,9/106 CМ) in the myocardium of adult patients. Significantly more left ventricle end-diastolic volume (100.4±36.6 and 75.8±18.5 ml, p=0.01) and less proliferative active cardiomyocytes (146/106 CМ and 2261/106 CМ, p=0.002) were revealed in the patients who received angiotensin-converting enzyme inhibitors. Significantly less proliferative active mature cardiomyocytes (1092/106 CM and 3084/106 CМ, p=0.008)and resident cardiac stem cells (1091/106 CМ and 8224/106 CМ, p=0.01) were revealed in the patients who received beta-adrenergic blocking agents. Significantly less cardiac hystiocyte hypertrophy intensity (22.9±4.9 and 26.7±4 mkm, p=0.018) and less proliferative active small cardiomyocytes (981/106 CМ and 2261/106 CМ, p=0.02) were revealed in the patients who received aldosterone antagonists.
Conclusion. Angiotensin-converting enzyme inhibitors and aldosterone antagonists influence myocardial proliferative potential and development of myocardial hypertrophy due to proliferative active small cardiomyocytes loss. Aldosterone antagonists influence cardiomyocytes hypertrophy intensity facilitating their decrease. І-adrenoblockers facilitate myocardial resident stem cells loss and decrease mature cardiomyocytes proliferative activity. Thus blocking sympathetic system and various components of renin-angiotensin-aldosterone system results in myocardial proliferative potential loss and facilitates development rates loss of myocardial hypertrophy which should be taken into consideration in the treatment of patients with hypertrophic cardiomyopathy, particularly obstructive form.

References

Чудиновских Ю.А. Резидентные стволовые клетки сердца и их роль в развитии гипертрофии миокарда: Дис. ... канд. мед. наук. М., 2011. 136 с.

              <br>Brilla C. et al. The cardiac structure-function relationship and the renin-angiotensin-aldosterone system in hypertension and heart failure // Curr. Opin. Cardiol. 1994. Vol. 9. (Suppl.). Р. 2-10.

              <br>Cambronero F., Marin F. et al. Biomarkers of pathophysiology in hypertrophic cardiomyopathy: Implications for clinical management and prognosis // Eur. Heart J. 2009. Vol. 30. Р. 139-151.

              <br>Cingolani H. E., Ennis I. L. Sodium-hydrogen exchanger, cardiac overload, and myocardial hypertrophy // Circulation. 2007. Vol. 115, № 9. Р. 1090-1100.

              <br>Karamzin M., Que Liu et al. Aldosterone increases NHE-1 expression and induces NHE-1-dependent hypertrophy in neonatal rat ventricular myocytes // Hypertension. 2003. Vol. 42. Р. 1171-1177.

              <br>Maron B.J., McKenna W.J., Danielson G.K. et al. American College of Cardiology/ European Society of Cardiology Clinical Expert Consensus Document on Hypertrophic Cardiomyopathy. A report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for Practice Guidelines// JACC. 2003. Vol. 42. Р. 1687-1713.

              <br>Maron B.J., Towbin J.A., Thiene G. et al. Contemporary definitions and classification of cardiomyopathies // Circulation. 2006. Vol. 113. Р. 1807-1816.

              <br>Sciarretta S., Paneni F., Chin D. et al. Role of the renin-angiotensin-aldosterone system and inflammatory processes in the development and progression of diastolic dysfunction // Clinical Science. 2009. Vol.116. Р. 467-477.

              <br>Sun Y., Weber K. T. Cardiac remodelling by fibrous tissue: Role of local factors and circulating hormones// Ann. Med. 1998. Vol. 30 (Suppl.). Р. 3-8.

              

 If you found mistakes, select text and press Alt+A