СЦИНТИГРАФИЯ МИОКАРДА С 123I-МЕТАЙОДБЕНЗИЛГУАНИДИНОМ В ОЦЕНКЕ СИМПАТИЧЕСКОЙ ИННЕРВАЦИИ МИОКАРДА ЛЕВОГО ЖЕЛУДОЧКА У БОЛЬНЫХ ИШЕМИЧЕСКОЙ БОЛЕЗНЬЮ СЕРДЦА С ФИБРИЛЛЯЦИЕЙ ПРЕДСЕРДИЙ

The aim of this study was assessment of cardiac sympathetic activity in patients with atrial fibrillation by planar scintigraphy with 123I-metaIodbenzilguanidine (123I-MIBG).Material and Methods. The study included 28 (average age (57.4 ± 11.6) years) patients with suspected coronary artery disease. All patients to divide 3 groups: 13 patients (group 1) with paroxysmal AF (PAF),6 patients (group 2) with long-standing persistent AF (LSPAF) and 10 patients with no signs of AF (group 3).Planar imaging was performed to study initial (imaging started 20 minutes after MIBG injection 148 MBq 123I-MIBG) and delayed (imaging started 4 hours after 123I-MIBG injection). For the anterior planar 123I-MIBG images, regions of interest were constructed for the heart and upper mediastinum, and the heart-mediastinal ratio (HMR).Results. The delayed HMR in patients with PAF and LSPAF was significantly lower compared that in patients third group (1.59 ± 0.16, 1.54 ± 0.17 and 1.82 ± 0.11 respectively, p < 0.05). The washout rate of 123I-MIBG in patients with PAF and LSPAF was significantly highest compared that in patients with no signs of AF (33.4 ± 17.5, 29 ± 11.7 and 17.2 ± 9.6 respectively, p < 0.05). In assessment of regional sympathetic activity in patients with LSPAF defect accumulation 123I-MIBG in both the early and delayed scintigrams was significantly higher compared with groups of patients with PAF and without AF.Results of this study indicated, that the patients with atrial fibrillation has of regional LV myocardial changes, according with 123I-MIBG imaging. More sympathetic innervation abnormality was observed in patients with long-standing persistent AF.С помощью сцинтиграфии с 123I-метайодбензилгуанидином (123I-МЙБГ) оценивали состояние симпатической иннервации миокарда левого желудочка (ЛЖ) у больных с фибрилляцией предсердий (ФП).Материал и методы. В исследование были включены 28 пациентов с диагнозом «стенокардия, ишемическая болезнь сердца I–II функционального класса», из них 12 больных с пароксизмальной формой ФП (ПФП), 6 больных с длительно персистирующей формой ФП (ДПФП) и 10 пациентов без признаков ФП. По данным планарной сцинтиграфии миокарда оценивали общую симпатическую активность по соотношению «сердце/средостение» (С/Ср) и скорости вымывания индикатора. По данным эмиссионной томографии оценивали регионарную симпатическую активность.Результаты. Анализ результатов показал, что у пациентов с ПФП и ДПФП значение соотношения С/Ср как на ранних, так и на отсроченных сцинтиграммах было достоверно ниже по сравнению с аналогичным показателем у больных без признаков ФП (1,59 ± 0,16; 1,54 ± 0,17 против 1,82 ± 0,11 на ранних сцинтиграммах и 1,49 ± 0,19; 1,46 ± 0,18 против 1,83 ± 0,13 на отсроченных сцинтиграммах соответственно, p < 0,05). Также у пациентов с ПФП и ДПФП была достоверно выше скорость вымывания индикатора по сравнению с группой пациентов без ФП (33,4 ± 17,5; 29 ± 11,7 против 17,2 ± 9,6 соответственно, p < 0,05). При оценке регионарной симпатической активности у пациентов с ДПФП дефект накопления 123I-МЙБГ как на ранних, так и на отсроченных сцинтиграммах был достоверно больше по сравнению с группами больных с ПФП и без ФП.Вывод. У пациентов с ФП имеют место выраженные изменения функционального состояния симпатической нервной системы миокарда ЛЖ по сравнению с группой пациентов без ФП. Наиболее значимые нарушения регионарной симпатической активности наблюдаются у пациентов с ДПФП

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease

NEUROTROPIC MYOCARDIAL SCINTIGRAPHY IN THE EVALUATION OF SUDDEN CARDIAC DEATH PROGNOSIS IN PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY

Objective. To explore the features of cardiac sympathetic activity impairments using neurotropic scintigraphy and singlephoton emission tomography (SPECT) in patients with hypertrophic cardiomyopathy (HCM), including the context of the risk of sudden cardiac death (SCD).Material and methods. 36 patients with HCM, II–IV NYHA CHF grade, underwent cardiac neurotropic scintigraphy and SPECT with 123I-MIBG. 30 patients also underwent cardiac perfusion SPECT with 99mTc-MIBI, standard quantitative parameters of global and local left ventricular sympathetic activity and perfusion impairments were obtained. After 5 years of follow-up, the analysis of the dependence of the frequency of SCD in patients with HCM on the values of the above parameters was performed.Results. All parameters of perfusion and neurotropic myocardial SPECT were significantly different in patients with HCM compared with the control group (p<0.001). According to perfusion SPECT data, significant transient ischemia of the myocardium (SDS>4) in the main group was detected in 32% of cases, while it had a diffuse character and had no connection with certain coronary artery regions. The volume of regional innervation defects (SMSe) in HCM patients significantly exceeded the total volume of perfusion defects (SSS, p<0.001). SMSe and SSS parameters had a direct correlation (r=0.52, p=0.002). SMSe was higher in patients with HCM with arrhythmias (p=0.046), and lower in patients with HCM with manifestations of angina and cardialgia (p=0.04). Based on the results of a five-year follow-up, SCD occurred in 8 patients with HCM. SMSe was a predictor of SCD (AUC=0.76, p=0.01), its value >14 predicted the occurrence of SCD with sensitivity of 87.5% and specificity of 57.1%. The risk of five-year mortality from SCD was significantly higher when SMSe >14 (p=0.024). Conclusion. Neurotropic SPECT in patients with HCM is able to identify a group of patients at high risk of sudden cardiac death

Superimposed single-photon emission computed tomography and X-ray computed tomography of the heart: Methodical aspects

Global radiology and nuclear medicine have recently shown a clear trend towards hybrid (combined, superimposed) studies. Unfortunately, the Russian literature virtually lacks both methodological and research works on this topic. The basis for this paper was the guidelines of the North American Society of Nuclear Medicine and Molecular Imaging, the North American Society of Nuclear Cardiology, and the Society of Cardiovascular Computed Tomography and the principles as jointly set out by the European Society of Nuclear Medicine, the European Society of Radiology, and the European Association of Nuclear Medicine.The purpose of the paper is to familiarize readers with some methodical aspects of performing superimposed single-photon emission computed tomography (SPECT) and X-ray computed tomography (CT) of the heart. This publication discusses the main indications for and contraindications to hybrid cardiological studies and gives other data that are useful to select patients for examination. A patient's preparation and prevention measures are described. There is information on major radiotracers and equipment for superimposed studies. There are imaging parameters and information on the correction of gamma-ray quantum absorption according to CT data. The paper concerns the interpretation of the results of identifying coronary artery calcification and those of CT coronarography and myocardial perfusion scintigraphy. It presents the methodical aspects of superimposition of radionuclide and CT images, the possible sources of errors during superimposed SPECT/CT, and recommendations for making a diagnostic conclusion. The issues of radiation load and radiation safety are discussed

SCINTIGRAPHIC ESTIMATION OF THE SYMPATHETIC INNERVATION OF THE HEART AND MYOCARDIAL PERFUSION IN PATIENTS WITH ATRIAL FIBRILLATION

Aim. The aim of the study was to scintigraphically evaluate the condition of sympathetic innervation of myocardium and coronary microcirculation in patients with atrial fibrillation (AF).Material and methods. Totally 40 patients included with CHD II-III functional class and AH III stage. Of those: 15 patients — with paroxysmal AF (PAF), 15 — with long-lasting persistent AF (LPAF) and 10 patients — without any signs of AF. To evaluate the sympathetic activity of the myocardium all patients underwent scintigraphy with 123I-metaiodbenzylguanidine (123I-MIBG). With planary study of myocardium investigation with 123I-MIBG we assessed regionary sympathetic activity by the relation of “Heart/ Mediastinum” (H/M) and speed of indicator washout. Also all participants underwent myocardial scintigraphy with 99mTc-MIBG to measure coronary microcirculation.Results. Analysis of the data showed that patients with PAF and LPAF the relation of H/M at early and delayed scintigrammes was significantly lower comparing to the same value in the patients without AF (1,57±0,15, 1,54±0,18 vs. 1,82±0,12 on early scintigrammes and 1,47±0,15, 1,46±0,16 vs. 1,83±0,13 on delayed, with p<0,05). Also in PAF and LPAF was significantly higher the velocity of indicator excretion comparing to the group of patients without AF (31,2%±11,5%, 29,4%±10,5% vs. 17,5%±10,3%, resp., p<0,05). By the evaluation of regional sympathetic activity in patients with LPAF the filling defect of 123I-MIBG on early and delayed scintigrammes was significantly higher than in groups with PAF and without AF. In evaluation of coronary microcirculation there were no any significant differences of the perfusion defect among the groups studied.Conclusion. The study showed that in patients with AF there are the most prominent changes in functional conditions of myocardial sympathetic system comparing to the group without AF. At the same time AF does not lead to significant influence on myocardial flow, and the most significant disorders of regional sympathetic activity are visible in patients with long persistent AF