ISSN 2409-9988 2017 N2(4) INTER COLLEGАS 2017 Vol. 4 No.2 OFFICIAL JOURNAL OF KHARKIV NATIONAL MEDICAL UNIVERSITY ISSN 2409-9988 EDITOR-IN-CHIEF: Vladimir Lesovoy, MD, PhD, professor, rector of KNMU EDITORIAL BOARD: Tetiana Ashcheulova, MD, PhD, professor, KNMU Valeriy Boyko, MD, PhD, professor, KNMU Olga Kovalyova, MD, PhD, professor, FESC, KNMU Volodymyr Korostiy, MD, PhD, professor, KNMU Vitalii Makarov, MD, PhD, professor, KNMU Olena Riga, MD, PhD, professor, KNMU Evhen Ryabokon, MD, PhD, professor, KNMU Igor Taraban, MD, PhD, professor, KNMU Iryna Tuchkina, MD, PhD, professor, KNMU Tetyana Chumachenko, MD, PhD, professor, KNMU Igor Zavgorodnii, MD, PhD, professor, KNMU Gulya Alimbayeva, MD, PhD, Associate professor, Kazakh National Medical University, Almaty, Kazakhstan Irina Böckelmann, MD, PhD, professor, Otto-von-Guericke-Universität, Magdeburg, Deutschland Ala Curteanu, MD, PhD, Associate professor, Mother And Child Institute, Chisinau, Moldova Igor Huk, MD, PhD, professor Vienna General Hospital, University Medical School, Vienna, Austria Birgitta Lytsy, MD, PhD, Uppsala University, Sweden Ed Maes, MD, PhD, Centers for Disease Control and Prevention, Atlanta, Georgia, USA Gayane G. Melik-Andreasyan, MD, PhD, professor, Director of Research Institute of Epidemiology, Virology and Medical Parasitology after A.B.Alexanian, Yerevan, Armenia Branislav Milovanovic, MD, PhD, professor, University Hospital Bezanijska Kosa, Belgrade, Serbia Peter Nilsson, MD, PhD, professor, Lund University, Malmo, Sweden. Elmars Rancans, MD, PhD, professor, Riga Stradins University, Latvia Adam Rzechonek, MD, PhD, Associate professor, Wroclaw Medical University, Poland Milko Sirakov, MD, PhD, professor, President of European Association of Paediatric and Adolescent Gynaecology, Bulgary Arunas Valiulis, MD, PhD, professor, Clinic of Children's Diseases and Institute of Public Health, Vilnius University Medical Faculty, Vilnius, Lithuania DEPUTY EDITOR: Valeriy Myasoedov, MD, PhD, professor, vice-rector of KNMU ASSOCIATE EDITORS: Vitaliy Gargin, MD, PhD, professor, KNMU Volodimir Korobchanskiy, MD, PhD, professor, KNMU EXECUTIVE SECRETARY: Tetyana Chaychenko, MD, PhD, associate professor, KNMU Recommended for publishing by Scientific Council of Kharkiv National Medical University 29 - Jun - 2017 Correspondence address: 61022, Kharkiv, Nauki Avenue, 4 e-mail: collegas@ukr.net URL: http://inter.knmu.edu.ua/pub Periodicity: 4 times a year © Inter Collegas, 2017 mailto:collegas@ukr.net INTER COLLEGAS, VOL. 4, No. 2 (2017) ~ 50 ~ ISSN 2409-9988 Table of Contents MEDICAL HISTORY LEGAL REGULATION OF MEDICAL ACTIVITY IN RUSSIAN EMPIRE BY MEDICAL CHARTER PDF Novikov D.O. 52-56 CARDIOLOGY & CARDIAC SURGERY INTRAOPERATIVE TYPE A AORTIC DISSECTION REPAIR (case report) PDF ABDURAKHMANOV A.A., OBEID M.A., EHRLICH M. 57-60 METFORMIN AND LEFT VENTRICULAR HYPERTROPHY IN PATIENTS WITH COMORBIDITY DEMYDENKO G. 61-64 PEDIATRICS MODERN VIEWS OF GERD IN CHILDREN: PROBLEMS AND PERSPECTIVES (review) PDF Slobodianiuk O.L. 65-71 PARTICULAR QUALITIES OF THE TREATMENT IN PRE-SCHOOL AGE CHILDREN SENSITIZED TO HOUSE DUST MITES ALLERGEN PDF Sharikadze O.V. 72-78 DIAGNOSIS EVALUATION OF INFANT DEVELOPMENT USING A GUIDE FOR MONITORING CHILD DEVELOPMENT PDF Riga O.O., Gonchar M.O., Uryvayeva M.K., Samsonenko V.I., Shulga A.A. 79-82 ALAGILLE SYNDROME AS A CHALLENGING CLINICAL CASE IN PEDIATRIC PRACTICE (case report) PDF Hajiyeva N.A. 83-85 DIAGNOSIS AND TREATMENT OF SEPSIS IN AN INFANT WITH CONGENITAL LACTASE INSUFFICIENCY (case report) PDF Sirenko T.V., Plahotna O.N., Zdybskaya E.P., Khalturyna T.A., Gaidamaka L.N. 86-90 http://inter.knmu.edu.ua/pub/article/viewFile/46/45 http://inter.knmu.edu.ua/pub/article/view/46 http://inter.knmu.edu.ua/pub/article/viewFile/46/45 http://inter.knmu.edu.ua/pub/article/view/46 http://inter.knmu.edu.ua/pub/article/viewFile/45/44 http://inter.knmu.edu.ua/pub/article/view/46 http://inter.knmu.edu.ua/pub/article/view/46 http://inter.knmu.edu.ua/pub/article/viewFile/45/44 http://inter.knmu.edu.ua/pub/article/view/46 http://inter.knmu.edu.ua/pub/article/viewFile/45/44 http://inter.knmu.edu.ua/pub/article/viewFile/45/44 http://inter.knmu.edu.ua/pub/article/view/46 http://inter.knmu.edu.ua/pub/article/view/46 http://inter.knmu.edu.ua/pub/article/viewFile/45/44 INTER COLLEGAS, VOL. 4, No. 2 (2017) ~ 51 ~ ISSN 2409-9988 A CLINICAL CASE OF SUCCESSFUL REHABILITATION OF A CHILD WITH UNDINE SYNDROME (CCHS-CONGENITAL CEN- TRAL HYPOVENTILATION SYN-DROME, ONDINE SYNDROME, OMIM 209880) PDF Grechanina Yu., Bugaeva E., Biletska S. 91-95 PSYCHIATRICS EXPERIENCE OF EXTENDING ANTIPSYCHOTIC AID TO WOMEN WITH EPILEPSY COMPLICATED BY PSYCHOTIC DISORDERS PDF Strelnikova I. M., Kozhina H. M. 96-101 http://inter.knmu.edu.ua/pub/article/view/45 http://inter.knmu.edu.ua/pub/article/view/45 http://inter.knmu.edu.ua/pub/article/viewFile/45/44 http://inter.knmu.edu.ua/pub/article/viewFile/45/44 INTER COLLEGAS, VOL. 4, No. 2 (2017) ~ 61~ ISSN 2409-9988 CARDIOLOGY Demydenko G.V. METFORMIN AND LEFT VENTRICULAR HYPERTRO- PHY IN PATIENTS WITH COMORBIDITY Kharkiv National Medical University, Ukraine Abstract: Essential hypertension (EH) remains an important challenge, due to leading positions in morbidity and mortality not only in Ukraine, but also worldwide. Recent studies have suggested that metformin can inhibit cardiomyocyte apoptosis and improve cardiac function. Aim of the study was to investigate metformin influence on left ventricular structure and function in patients with essential hypertension with concomitant type 2 diabetes (T2D). Materials and methods: the study involved 120 patients with essential hypertension (EH), who were divided into three groups according to comorbid state: 60 patients with EH and T2D; 30 with EH with prediabetes; 30 with EH without dysglycemia. Carbohydrate criteria, left ventricle structure and function were analyzed before and after 12 weeks of metformin treatment. Results. Metformin treatment results in fasting glycaemia and insulin resistance diminished by 21.79 % and 26.84 %. Echocardiography in 12 weeks metformin treatment showed a significant decrease in left ventricle myocardium mass by 6.1 % and left ventricle posterior wall thickness by 2.3 %. More pronounced changes in patients with EH and T2D were associated with glucotoxicity, lipotoxicity, a decrease in insulin resistance and pleiotropic metformin effects. Conclusion. Metformin has positive influence on the structure and function of left ventricle, increasing EDV and LV hypertrophy regression. These findings may provide a potential effectiveness for patients with T2D at risk of developing pathological cardiac hypertrophy. KeyWords: essential hypertension, type 2 diabetes, left ventricle hypertrophy, metformin. ———————————————————— INTRODUCTION Essential hypertension (EH) remains an important public challenge, because of its leading positions in mor- bidity and mortality not only in Ukraine, but also world- wide [1]. Hypertension in obese patients in over 60% of cases is associated with glucometabolic disturbances, such as insulin resistance and glucose intolerance [2]. Moreover, diabetes develops in 2 % of treated hy- pertensive patients every year [3, 4]. Pathological left ventricular hypertrophy is a crucial pathological condition that triggers several serious cardiac events, including ar- rhythmias, heart failure, and sudden death. Recent studies have suggested that metformin can inhibit cardiomyocyte apoptosis and improve cardiac function [5]. However, whether metformin has an inhibitory effect on cardiac hypertrophy hasn’t been clarified. ———————————————— Corresponding Author: Demydenko Ganna, PhD, professor of Department of Fundamentals of Internal Medicine N1, Fundamentals of Bioethics and Biosafety of Kharkiv National Medical University. E-mail: demydenkoganna@gmail.com 2.1 Purpose Aim of the study was to investigate metformin’s influence on left ventricular structure and function in patients with essential hypertension with concomitant type 2 diabetes (T2D). 2.2 Subjects & Methods The study involved 60 patients with EH and T2D, who were examined according to National and European Recommendations of T2D Treatment [6, 7]. Metformin was prescribed after titration period in average dosage of 1000 – 2000 mg. Comparison group comprised 30 patients with EH and prediabetes. Also 30 patients with EH without accompanied dyglycemia were recruited in the study. Antihypertensive treatment was similar in the groups. Taking into account that metformin is not allowed for prescription to the patients with prediabetes, such patients received life style modification recommendations. The results were analyzed before and in 12 weeks treatment period. The aim of antihypertensive treatment was to achieve the level of arterial pressure of ≤ 140/85. Antiglycemc treatment was consideredsuccessful in case of HbA1c level ≤ 7 %. mailto:demydenkoganna@gmail.com INTER COLLEGAS, VOL. 4, No. 2 (2017) ~ 62 ~ ISSN 2409-9988 Inquiring, inspection and laboratory investigations were provided according to the recommendations of Ukrainian Society of Cardiology and ESC/ESH recommendations [8]. The study was approved by local institutional review board committees, and all participants provided written informed consent. All subjects underwent measurements of height, weight at the baseline visit. Body mass index (BMI) was calculated as weight in kilograms divided by the square of the height in meters (kg/m2). Three measurements of systolic blood pressure (SBP) and diastolic blood pressure (DBP) were taken using a standardized sphygmomanometer on the right arm, after a 15-minute rest in a sitting position; the average of the three measurements was used as subject’s blood pressure. A blood specimen was collected after overnight fasting into a tube with further centrifuging and freezing for investigations. Carbohydrate metabolism was evaluated on the basis of plasma glucose, insulin, glycated hemoglobin (HbA1c) that were measured both at fasting, and after 120 min of standard glucose tolerance test (OGTT). For insulin measurements the laboratory set DRG® Insulin (DRG Instruments GmbH, Germany, Marburg) was used. Echocardiography was rendered to all the patients. М- і В-regimens of echolocation according to Ukrainian and European recommendations were used to estimate the structure and function of the left ventricle. [9] Statistical representation of the results is mean and standard error of mean (M±SE). The difference between groups was calculated using Kruskal-Wallis test. A p value of less than 0.05 was considered to be statistically significant. Conflict of interests There is no conflict of interests. 3 RESULTS AND DISCUSSION Last decade showed many cardiovascular effects of metformin, which seemed significant in prophylaxis and control of cardiovascular diseases. First UKPDS study showed a 36 % decrease in all deaths, 42 % in T2D, a 39 % decrease in myocardial infarction lethality and 41 % in stroke [10]. Scientific data suggest that cardioprotective effects of metformin are associated with lipid the enhancement of metabolism, improvement of endothelial function and vessel reactivity, control of hemostatic disorders [11 - 13]. As previously shown in our study, metformin treatment resulted in a decrease in fasting glycemia and insulin re- sistance by 21.79 % and 26.84 % and reduction in ab- dominal fat deposition by 5.54 %. Improvement of endothe- lial function in metformin treatment was associated with an increase in endothelial nitric oxide synthase by 8.43%, a decrease in inducible nitric oxide synthase by 20.62 %, with nitric oxide bioavalibility enhancement by 36.6 % by decreasing S-nitrozothiol level. Twelve weeks of metformin treatment showed a positive trend not only in carbohy- drate and lipid parameters with insulin sensitivity and endothelial function improvement, but it also resulted in an increase in apelin level by 33.3 %, attenuating of vascu- lar endothelial growth factor by 22.0 %, a decrease in on- costatin M and interleukin-6 by 18 % and 15 %, respectively. [14, 15]. Therefore, assessing the obtained data, we are looking for metformin impact on LV. Table 1 presents crite- ria of LV structure and function according to dysglycemia level. Linear sizes were found to increase in patients with EH and comorbid state as compared to patients with EH without dysglycemia. LV myocardial wall thickness and LV myocardial mass were significantly higher in case of EH and T2D comorbidity. Table 1. Left ventricle structure and function criteria in patients with EH according to comorbid state, Me±SЕ. Group Parameter Patients with EH Patients with EH and predi- abetes Patients with EH and T2D р (Krus- kal- Wallis ANOVA) EDS, cm 4.86±0.05 5.05±0.07 4.91±0.07 >0.05 ESS, cm 3.08±0.05 3.30±0.05 3.14±0.06 >0.05 EDV, ml 112.21±2.8 122.44±4.3 115.70±3.8 >0.05 ESV, ml 38.39±1.48 45.96±3.37 40.82±2.08 >0.05 PWT, cm 1.14±0.01 1.12±0.02 1.18±0.02 <0.05 LVММ, gr 214.51±6. 213.44±8.4 224.96±8.8 <0.05 EDS – end-diastolic size; ESS – end-systolic size; EDV - end- diastolic volume; ESV – end-systolic volume; PWT – posterior wall thickness; LVММ – left ventricle myocardial mass Echocardiography in 12 weeks of metformin treatment (Table 2) showed a significant decrease in LVMM by 6.1 %, LVT by 2.3 %. Patients with EH with concomitant prediabe- tes and without comorbidity were not shown to have signif- icant differences in LV EDV, PWT, LVMM. More pronounced INTER COLLEGAS, VOL. 4, No. 2 (2017) ~ 63 ~ ISSN 2409-9988 changes in patients with EH and T2D were associated with glucotoxicity, lipotoxicity, a decrease in insulin resistance and pleiotropic metformin effects [16]. Table 2 LV structure and function parameters in patients with EH and T2D after 12 weeks metformin treatment, as com- pared to patients with EH and prediabetes and ones without comorbid state. Parameter Group EDS, сm ESS, cm EDV, ml ESV, ml PWT, cm LVMM, g Patients with EH 4.66± 0.05 3.04± 0.05 109.9 ±1.95 37.92 ±2.02 1.11± 0.02 211.21 ±5.85 Patients with EH and prediabetes 5.01± 0.02 3.25± 0.05 120.9 ±3.12 45.06 ± 2.65 1.11± 0.02 210.30 ±6.02 Patients with EH and T2D 4.78± 0.05 3.10± 0.02 112.8 ±2.65* 40.78 ±2.01 1.15± 0.02* 211.46 ±5.41* р (Kruskal- Wallis ANOVA) >0.05 >0.05 <0.05 >0.05 >0.05 <0.05 *- р <0.001 (Wilcoxon test), comparing to data before treat- ment; EDS – end-diastolic size; ESS – end-systolic size; EDV - end-diastolic volume; ESV – end-systolic volume; PWT – poste- rior wall thickness; LVММ – left ventricle myocardial mass The MET-REMODEL, a double blind, randomized, place- bo-controlled trial showed that metformin was effective in regression of the independent cardiac risk factor of LVH in insulin resistant patients with CAD. Positive result may help clinicians identify a new mechanism for LV regression by administering metformin. This may also lead to investi- gating the mortality benefit of Metformin in patients with CAD and LVH [17]. Metformin is known as an activator of AMP-activated protein kinase (AMPK). Zhang C.X. et al. used cultured cardiomyocytes to examine the effects of metformin on the AMPK-endothelial NO synthase (eNOS) pathway. The findings of the study indicated that long-term treatment with metformin could attenuate ventricular hypertrophy induced by pressure overload via activation of AMPK and a downstream signalling pathway involving eNOS-NO [18] The investigation of the Yong-nan Fu revealed that long- term administration of metformin may attenuate cardiac hypertrophy induced by pressure overload in nondiabetic mice, and this attenuation is highly dependent on AMPK activation. 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