EFFECTIVENESS OF PHARMACOTHERAPY FOR NORMALIZATION OF THE BRAIN NATRIURETIC PEPTIDE, RENINE-ANGIOTENSINALDOSTERONE SYSTEM ACTIVATION AFTER SURGICAL REVASCULARIZATION OF MYOCARDIUM IN POSTINFARCTION CARDIOSCLEROSIS PATIENTS

Aim.  The  research  on  medical  technologies   for  optimization  of complication prevention and of post-surgery management of patients with coronary heart disease  (CHD) with ejection fraction (EF) of the left ventricle (LV) <40% in surgical revascularization of the heart.

Material and methods. In the controlled, randomized study of 103 CHD patients with severe systolic dysfunction of the LV, the effectiveness  of aortic  coronary  bypass  surgery  was  studied.  All  patients  underwent clinical investigations,  where  the  severity of patient’s  condition  was assessed, as the risks of surgery by EuroSCORE, severity of heart failure signs  by the  clinical condition  scale,  echocardiography, clinical and chemistry lab. Aldosterone levels were studied  with immune enzyme assay,  brain natriuretic peptide  — with immune enzyme assay,  redox potential (NAD/NADP) with the Sigma-Aldrich system, procollagen III of N-end peptide — with the test-system USCN, Statistics was done on the software Statistica 8.0.

Results. The inclusion to pre-operation  preparing of patients  of a drug with positive inotropic properties  and decreasing the level of systemic inflammation syndrome, dosage of 2 ampules intravenously during 3 days before operation and with following 7-day post-surgery, in CHD patients with significant LV  dysfunction  influences  positively the  symptoms  of chronic heart failure, initiates the deremodeling of the heart — significantly decreases the end-systolic size and increases EF LV, reduces  pulmonary hypertension, significantly decreases the duration of artificial ventilation, timing of inotropic support, duration of stay in ICU. It is shown that the level of brain  natriuretic  peptide  (NT-proBNP) in plasma  does  negatively correlate  with EF LV (r=-0,69,  p<0,01)  and redox-potential  NAD/NADP (r=-0,89; p=0,0001). At the background of Adenotsin® treatment there is significant decrease of NT-proBNP level by the 7th day after operation by 55%, the level of renin decreases, of aldosterone  and procollagen type III in blood, that confirms the positive prognosis of treatment.  There are no negative events in the drug course of implication for the studied category of patients.

1. Bockeria LA, Alshibaya MM, Bendeliani NG, et al. Secondary prevention of cardiovascular complications in the late period after surgical treatment of ischemic heart disease in the context of practical health service. Clin Physiol Circulation 2011; 4: 69-75. Russian (Бокерия Л. А., Алшибая М. М., Бенделиани Н. Г. и др. Вторичная профилактика сердечно-сосудистых осложнений в отдаленном периоде после хирургического лечения ишемической болезни сердца в условиях практического здравоохранения. Клиническая физиология кровообращения 2011; 4: 69-75).

2. Bokeria LA, Busiashvili IIu, Alshibaya MM, et al. Treatment of patients with coronary heart disease and postinfarction rupture of interventricular septum: actual questions at present. Cardiology & Cardiovascular Surgery 2012; 1: 5-12. Russian (Бокерия Л. А., Бузиашвили Ю. И., Алшибая М. Д. и др. Лечение больных ишемической болезнью сердца с постинфарктным разрывом межжелудочковой перегородки: актуальные вопросы на современном этапе. Кардиология и сердечно-сосудистая хирургия. 2012; 1: 5-12).

3. Cannata A, Camparini L, Sinagra G, et al. Pathways for salvage and protection of the heart under stress: novel routes for cardiac rejuvenation. Cardiovasc Res 2016; 111: 142-53.

4. Kunadian V, Pugh A, Zaman AG, et al. Percutaneous coronary intervention among patients with left ventricular systolic dysfunction: a review and meta-analysis of 19 clinical studies. Coron Artery Dis 2012; 23(7): 469-79.

5. Hamad MAS, van Straten AHM, Schonberger JPAM, et al. Preoperative ejection fraction as a predictor of survival after coronary artery bypass grafting: comparison with a matched general population. J Cardiothoracic Surgery 2010; 5: 29-40.

6. Zannad F. Aldosterone and heart failure. Hypertension 2014; 16: 98-102.

7. Lange JM. Discontinuation of renine angiotensine aldosterone blockade system did not reduced post coronary surgery renal failure. Int J Cardiovasc Res 2015; 4: 6-12.

8. Edelman F, Tomachitz A, Wachter R, et al. Serum aldosterone and its relationship to left ventricular structure and geometry in patients with preserved left ventricular ejection fraction. Eur Heart J 2012; 33 (2): 203-12.

9. Tziakas DN, Chalikias GK, Stakos D, et al. Independent and additive prognostic ability of serum carboxy-terminal telopeptide of collagen type-I in heart failure patients: a multi-marker approach with high-negative predictive value to rule out long-term adverse events. European. J Cardiovasc Prevention & Rehabilitation 2012; 19: 62-71.

10. Lopez B, Gonzalez A, Hermida N, et al. Myocardial fibrosis in chronic kidney disease: potential benefits of torasemide. Kidney Int 2008; 74(suppl 111): S19-23.

11. Sukoyan GV, Oganov RG. Signal mechanisms of cardioprotection and new strategies for heart failure prevention and treatment. Profilac Medicine 2012; 15(2): 23-32). Russian (Сукоян Г. В., Оганов Р. Г. Сигнальные механизмы кардиопротек-ции и новые стратегии превенции и лечения сердечной недостаточности. Профилактическая медицина 2012; 15(2): 23-32).

12. Donetskaya OP, Tulupova VA, Shuldeshova NV, et al. Pharmacological correction of plasma redox-potential and endothelial dysfunction in ischemic heart failure. Cardiovascular Therapy and Prevention 2012; 11(1): 54-8. Russian (Донецкая О. П., Тулупова В. А., Шульдешова Н. В. и др. Фармакоррекция редокс-потенциала плазмы и дисфункции эндотелия при сердечной недостаточности, обусловленной ишемической болезнью сердца. Кардиоваскулярная терапия и профилактика 2012; 11(1): 54-8).

13. Pillai VB, Sundaresan NR, Kim G, et al. Exogenous NAD blocks cardiac hypertrophic response via activation of the SIRT3-LKB1-AMP-activated kinase pathway. J Biol Chem 2010; 3133-44.

14. Houtkooper RH, Auwerx J. Exploring the therapeutic space around NAD+. JCB 2012; 199(2): 205-9.

15. Fima M, Guido B, Paul McK, et al. Pro-B-Type Natriuretic Peptide1_TO Circulates in the General Community: Plasma Determinants and Detection of Left Ventricular Dysfunction. JACC 2011; 57: 1386-95.

16. Tomaschitz A, Marz W, Pilz S, et al. Aldosterone/renin ratio determines peripheral and central blood pressure values over a broad range. JACC 2010; 55: 2171-80.

17. Guggilam A, Cardinale JP, Mariappan N, et al. Central TNF inhibition in attenuated neurohumoral excitation in heart failure: a role of superoxide and nitric oxide. Basic Res Cardiol 2011; 106(2): 273-86.

18. Bockeria LA, Malikov VE, Arzymanyan MA, et al. Rational pharmacological correction of the systemic inflammatory response syndrome in patients with decrease contractile function. Bull. Cardiovasc Surgery. Hematologia 2008; 2: 45-53. Russian (Бокерия Л. А., Маликов В. Е., Арзуманян М. А. и др. Рациональная фармакор-рекция синдрома системного воспалительного ответа у больных со сниженной сократительной функцией сердца. Бюлл сердечно-сосудистой хирургии. Гематология 2008; 2: 45-53).

19. Verdin E. NAD+ in aging, metabolism, and neurodegeneration. Science 2015; 350(6265): 1208-13.

20. Wang S, Xing Z, Vosler PS, et al. Cellular NAD Replenishment Confers Marked Neuroprotection Against Ischemic Cell Death Role of Enhanced DNA Repair. Stroke 2008 39(9): 2587-95.