DYNAMICS OF THE FUNCTIONAL STATE OF THE GENOME OF THE PERIPHERAL BLOOD NEUTROPHILS IN PATIENTS WITH CHRONIC HEART FAILURE

Summary. The aim of the work was to study the cytogenetic changes of neutrophils indicators in the peripheral blood of patients with chronic heart failure (CHF), depending on its stage and dynamics influenced by complex therapy. Methods. The study involved 59 patients with CHF, the average age (68.2±7.3) years, 26 patients with CHF FC III NYHA (group I) and 33 – NYHA FC IV (group II). Depending on the treatment, the patients were divided into the protocols A (22 patients: 12 – with CHF FC III NYHA, 10 – with CHF FC IV NYHA, receiving basic therapy), B (25 patients: 14 – with CHF FC III NYHA, 11 – with CHF FC IV NYHA, treated by arginine glutamate in the complex treatment) and C (22 patients with CHF FC IV treated by arginine glutamate in the complex treatment and arginyl-alpha-aspartyl-lysyl-valyl-tyrosyl-arginine). General clinical examination was performed. Functional status of the genome (FSG) of peripheral blood neutrophils was evaluated by analysis of interphase nuclei according to Feulgen in modification of L.Ye. Kovalchuk. Index of chromatization (IC) was calculated by the ratio of cells (in their nuclei euchromatin dominates) to the number of cells with heterochromatin; nucleolus index (NI) – according to the ratio of nuclei that had nucleolus to all of the studied nuclei; figure of morphologically altered nuclei (MAN) – as percentage of cells with pathologically altered nuclei. Content of tumour- necrotizing factor alpha (TNFa) in the blood was determined by ELISA method. Statistical methods were used. Research results. Analysis of the research results revealed changes in cytogenetic parameters of peripheral blood neutrophils in patients with CHF, depending on its stage. IC reduction in patients of group I at 11.30%, group II - at 27.03% (p<0.05) was established compared with healthy, that may indicate a decrease in the activity of transcription, as the first step of gene expression, and decrease of cell differentiation. NI decreased in patients of group I at 16.64%, group II – at 33.44% (p<0.05) compared with healthy, indicating a reduction in total cell metabolism and functional activity violations of nucleolar apparatus that grow with increase of stage CHF. MAN index in patients of group I increased at 52.26%, group II – at 89.70% (p<0.05) compared with healthy vacuolated nuclei prevailed, with deep intussusceptions of karyolemma, with no euchromatin and heteropyknotic. Content TNFa in blood grew with increasing degree of heart failure: heart failure in patients with stage IIA it was (28.54±2.20) pg/ml (p<0.05), heart failure stage IIB – (53.07±2.96) pg/ml (p<0.05) compared to (19.25±1.23) pg/ml in healthy. The correlation between the MAN index and the content of TNFa in blood was (r = + 0.39; p<0.05), which indicates multiple-factor progression of CHF. After the performed treatment in patients with CHF who were treated with basic therapy, cytogenetic indicators of peripheral blood neutrophils probably did not change from baseline. The use of arginine glutamate in the complex treatment of patients according to the protocol B helped normalize the IC and NI and a significant reduction of MAN in the presence of CHF FC III in NYHA and less pronounced positive dynamics of indicators of FSG in the presence of CHF IIB stage FC IV in NYHA (p<0.05). In patients with CHF FC IV in NYHA the additional use of arginyl-alpha-aspartyl-lysyl-valyl-tyrosyl-arginine in the complex treatment helped to improve the effectiveness of treatment as for the positive dynamics of indicators of FSG peripheral blood neutrophils. Conclusions. Violation of the functional state of the genome is more pronounced in patients with CHF IIB stage FC IV in NYHA compared with patients with CHF IIA stage FC III in NYHA. The use of arginine glutamate and arginyl-alpha-aspartyl-lysyl-valyl-tyrosyl-arginine in the complex treatment of patients with CHF promotes positive dynamics of FSG indicators of peripheral blood neutrophils.