Методы диагностики эндотелиальной дисфункции

 Endothelial dysfunction as a crucial factor in the pathogenesis of cardiovascular diseases requires precise and effective diagnostic methods. The review highlights the currently used methods which can be divided into morphological, instrumental, and laboratory ones. Special attention is paid to the so called jar  test, which was  introduced by Professor V.A. Valdman in 1936. The jar test may  serve as a prototype of modern methods for endothelial function assessment.These diagnostic methods can help to identify functional endothelial disorders at the earliest stage. It will significantly expand the possibilities of primary prevention of cardiovascular and a number of other diseases through non-pharmacological and pharmacological correction of endothelial dysfunction.  Проблема эндотелиальной дисфункции как важного звена в патогенезе заболеваний сердечно-сосудистой системы предполагает внедрение эффективных и точных  диагностических методов. В обзоре освещаются наиболее актуальные из применяемых в научной и клинической практике методов, которые условно подразделены на морфологические, инструментальные и лабораторные. Отдельно упомянута предложенная еще в 1936 г. профессором В.А. Вальдманом эндотелиальная баночная проба, которая может служить прообразом современных методов исследования эндотелия.Данные диагностические методики могут способствовать  выявлению функциональных нарушений эндотелия на самом раннем донозологическом уровне, что позволит  существенно расширить возможности первичной профилактики сердечно-сосудистых и ряда других  заболеваний путем немедикаментозной и фармакологической коррекции эндотелиальной  дисфункции.

Изучение влияния приёма пищи на биодоступность, безопасность и переносимость лекарственного препарата Атериксен®, таблетки, 100 мг у здоровых добровольцев

The aim. The primary objective of the study was to evaluate the effect of food on the bioavailability of Aterixen® 100 mg tablet after single oral dose under fasting or fed conditions. The secondary objective was to evaluate the pharmacokinetic parameters, safety, and tolerability of Aterixen® 100 mg tablet after single oral dose under fasting or fed conditions. Materials and methods. Healthy male and female volunteers aged 18 to 45 years were included in the study. Due to lack of data about intra-individual variability of the main pharmacokinetic parameters of the active substance in Aterixen® (XC221GI, 1-[2-(1-Methylimidazol-4-yl)-ethyl]perhydroazin-2,6-dione), an adaptive group sequential approach was used in the study. At Stage I, 24 volunteers were randomized into 2 groups (12 in each group): Group 1 (sequence AAB) received treatment A (administration of the drug under fasting conditions) during period I, treatment A during period II and treatment B (administration of the drug under fed conditions) during period III, Group 2 (sequence BBA) received therapy B during period I, therapy B during period II, and therapy A during period III. In each study period, serial blood samples were collected before and throughout 12 h after administration of the study drug. The quantification of the active substance XC221GI in plasma samples was performed using a validated high-performance liquid chromatography method with mass spectrometric detection. Safety evaluation was performed on the basis of frequency and severity of adverse events (AEs) and serious adverse events (SAEs), which were registered based on complaints, physical examination, laboratory tests, and electrocardiography (ECG). Drug tolerability was evaluated in terms of proportion of volunteers who prematurely discontinued participation in the study due to AE/SAE. Results. 24 randomized volunteers completed the study in compliance with the approved study protocol. The averaged pharmacokinetic curves profiles of XC221GI had similar shapes under fasting and fed conditions. Confidence intervals for the ratio of the geometric means for the primary parameters (AUC(0-t) and Cmax) of XC221GI and AUC(0-∞) were within the 80-125 % acceptance interval, while a small in absolute value, but statistically significant differences were noted in time until Cmax is reached. Throughout the study, 2 volunteers reported AEs (low RBC count, low hemoglobin concentration, and low hematocrit value) after receiving the study drug under fed conditions. All reported AEs were mild. The relationship between AEs and the study drug product was assessed by investigator as doubtful. Conclusion. The results of this study indicate that food does not affect the bioavailability of Aterixen® 100 mg, tablets, and the single oral dose of 100 mg was safe and well tolerated by healthy volunteers.Цель исследования. Первичной целью исследования являлась оценка влияния приёма пищи на биодоступность лекарственного препарата Атериксен®, таблетки, 100 мг после его однократного приёма натощак и после еды. Дополнительная цель заключалась в оценке фармакокинетических параметров, безопасности и переносимости препарата Атериксен® при его однократном приёме в дозе 100 мг натощак и после приёма пищи. Материал и методы. В исследование включали здоровых добровольцев мужского и женского пола в возрасте от 18 до 45 лет. В связи с отсутствием данных о внутрииндивидуальной вариабельности основных фармакокинетических параметров действующего вещества препарата Атериксен® (XC221GI, 1-[2-(1-Метилимидазол-4-ил)-этил]пергидроазин-2,6-дион) в исследовании применялся адаптивный последовательный подход. На Этапе I было рандомизировано 24 добровольца (по 12 в каждой группе): группа 1 (последовательность ААВ) принимала терапию А (приём препарата натощак) в периоде I, терапию А в периоде II и терапию В (приём препарата после еды) в периоде III, группа 2 (последовательность ВВА) принимала терапию В в периоде I, терапию В в периоде II и терапию А в периоде III. В каждом периоде исследования у добровольцев отбирали образцы крови до и в течение 12 ч после приёма препарата исследования. Количественное определение действующего вещества XC221GI в образцах плазмы крови проводилось валидированным методом высокоэффективной жидкостной хроматографии с масс-спектрометрическим детектированием. Безопасность препарата оценивали по количеству и степени тяжести нежелательных явлений (НЯ) и серьёзных нежелательных явлений (СНЯ), зарегистрированных на основании жалоб, данных физикального осмотра, а также по изменениям лабораторных показателей и электрокардиографического исследования (ЭКГ). Переносимость исследуемого препарата оценивали по доле добровольцев, досрочно прекративших участие в исследовании из-за возникновения НЯ/СНЯ. Результаты исследования. 24 рандомизированных добровольца завершили исследование полностью в соответствии с одобренным протоколом исследования. Усреднённые профили фармакокинетических кривых XC221GI при приёме исследуемого препарата натощак и после приёма пищи имели близкие формы. Доверительные интервалы для отношений средних геометрических значений первичных показателей (AUC(0-t) и Cmax) XC221GI, а также AUC(0-∞) соответствовали пределам эквивалентности 80,00–125,00 %, при этом было отмечено небольшое по абсолютной величине, но статистически значимое различие по времени достижения максимальной концентрации исследуемого вещества. На протяжении исследования у 2 добровольцев при приёме препарата после приёма пищи отмечались НЯ в виде снижения количества эритроцитов, концентрации гемоглобина и значения гематокрита. Все зарегистрированные НЯ имели лёгкую степень тяжести. Связь НЯ с исследуемым препаратом по оценке врача-исследователя была расценена как сомнительная. Заключение. Результаты исследования показали отсутствие влияния фактора приёма пищи на биодоступность лекарственного препарата Атериксен®, таблетки, 100 мг, а также его безопасность и хорошую переносимость при однократном приёме здоровыми добровольцами в дозе 100 мг

Microbiological and epidemiological features of microbial associations in septic infections in surgical departments

Introduction: The problem of septic infections (SI) is still an actuality, despite the positive developments in the fight against infectious diseases Objective: The study of the microbiological and epidemiological characteristics of poly etiology of purulent-septic infections in surgical patient's general hospital Materials and methods: Isolation and identification of microorganisms was carried out by conventional methods. To identify clinical and epidemiological features performed a retrospective analysis of incidence, according to official registration in the recording and reporting hospital. Results: 108 strains of microorganisms were aallocated, belonging to the 11 species. Among Assiociants dominated by Staphylococcus aureus (35,18%), Acinetobacter baumannii and Staphylococcus epidermidis. Acinetobacter baumannii and Staphylococcus epidermidis predominated, and among Assiociants among monocultures. Enterobacter agglomerans, Proteus mirabilis recorded only in the association. For surgical patients the most frequent combination of established S.aureus, Staphylococcus epidermidis among themselves, as well as E.coli, Proteus spp., Entero-coccus spp. Most species of microorganisms occurred mainly in the form of associations. In general surgery the figure was equal to 64.3%, dominated by two-component association. The number of multidrug-resistant crops amounted to 25,1% (Acinetobacter baumannii, Staphylococcus aureus, Enterobacter agglomerans). Jaccard coefficient was highest for Staphylococcus aureus Staphylococcus epidermidis (68,9%) and Staphylococcus aureus c Acinetobacter baumannii (47,5%), which corresponds to the synergistic relationship. And in the associations and Staphylococcus epidermidis Acinetobacter koeffitsient 17.1 - has an antagonist relationship. The neutral attitude prevailed over the synergistic and antagonistic. The average incidence of polyetiology infections was 17 per 100. As a result of the study, the following clinical and epidemiological features of polyetiology of infections in surgical patients and risk factors for their development: the leading pathology in polyetiology infections - skin and subcutaneous tissue (70%). The age structure of patients was predominantly older age group (42 to 60), and the average age of the patients was 54. The main type of surgery - opening abscesses, phlegmon, limbs amputation. Poly etiology of infections in patients had more surgical interventions (70.1%) and it was found that more patients with infections were poly etiology necrectomy. Duration of hospital stay was 13.4 days on average. The intensity of the ABT was primarily a course. Conclusions: Organization of the microbiological monitoring of poly-etiology SI, is a necessary part of the surveillance of hospital infections

VENTRICULAR EXTRASYSTOLIA IN PATIENTS WITH NON-ST ELEVATION ACUTE CORONARY SYNDROME: ASSESSING THE RISK OF LIFE-THREATENING VENTRICULAR ARRHYTHMIAS (CLINICO-EXPERIMENTAL STUDY)

The study aimed to assess the risk of life-threatening ventricular arrhythmias (LTVA) in patients with non-ST elevation acute coronary syndrome (ACS) and ventricular extrasystolia (VE) developing in the first 24 hours of ACS. In 46 dogs, VE with early, postponed post-depolarisation, re-entry and ischemic mechanisms was modelled. In total, 168 patients with non-ST elevation ACS and Class II-V Lawn VE were examined. All patients underwent general clinical examination as well as the assessment of late ventricular potentials (LVP), QT interval dispersion (QTd), and heart rate turbulence (HRT). In the experimental study, persistent ventricular tachycardia and/or ventricular fibrillation developed in 100%, 75%, and 85,71% of the animals with early post-depolarisation, re-entry and ischemic VE mechanisms, respectively. In the clinical study, LTVA was observed in 13,76 % of ACS patients, including 69,32 % with arrhythmia development in the first 3 days. Positive predictive value for LVP, QTd>80 ms and pathologic HRT was no more than 42%. LTVA risk could be assessed by the formula: LTVAR = А ÷ В, where LTVAR is LTVA risk in units, A – linear deviation of corrected pre-ectopic interval (ms) for at least 20 ventricular extrasystoles, calculated separately for left and right VE, and B – analysed ventricular extrasystole number (per hour). LTVAR<0,5 could be a marker of high LTVA risk, with positive predictive value of 96,34%, in non-ST elevation ACS patients with VE

Clinical assessment of transoesophageal electrostimulation in first-diagnosed Type I atrial flutter

In total, 1283 patients with coronary heart disease and fist-diagnosed atrial flutter (AFL) episodes were followed up from 1996 to 2007. In all participants, AF was treated with transoesophageal electrocardiostimulation (TOECS). Sinus rhythm was restored in 83,48 %: in 67,3 % without any antiarrhythmic therapy (AAT), and in others - with AAT before TOECS. The best effect was observed in patients receiving amiodarone or its combination with chinidin durules. Only in 2,88 %, AFL or atrial fibrillation remained after TOECS

EVALUATION OF HEART RATE AUTONOMOUS REGULATION IN PATIENT AFTER MYOCARDIAL INFARCTION

200 coronary patients after a myocardial infarction were studied in order to examine the influence myocardial infarction (MI) localization and depth, as well as sex and age, complications, concomitant conditions and treatment may have on heart rate variability (HRV). HRV was evaluated on the 10-14th day of myocardial infarction with a 5-minutes ECG record. Women demonstrated longer RR intervals, predominant CV, dRR, NN50 and RMSSD, tended to have higher TP and SD, LF/HF, IN and IRV were greater than in men. Thus women had higher parasympathetic tone. Age showed no influence on HRV, most likely because almost all patients were within the same age group (52-62 years). In inferior-posterior MIs as compared to anterior %LF was decreased and %HF, %VLF were higher, reflecting greater vagal tone in inferior MIs. In Q-MIs decreased SD and TP were observed. Concomitant hypertension increased the impact of %VLF, implying switch of regulation to a lower humoral-metabolic level . Concomitant diabetes mellitus decreased NN50, LF/HF, VPR, IRV and IN, reflecting cardiac neuropathy. Exacerbation of heart failure demonstrated worsened HRV and markedly decreased %HF and HFnu, implying parasympathetic influences being most depressed. Early postinfarctional angina was associated with greater LFnu and %LF, also reliably decreasing %VLF which is mot likely due to significant stress of the sympathetic branch. b-Blockers increased RR, increasing RMSSD, NN50 and %HF, demonstrating vagal influence under their action. ACE inhibitors shortened RR increasing HFnu and decreasing %VLF implying activation of the parasympathetic branch of the nervous system with simultaneously decreased humoral and metabolic influences. There were no differences in HRV depending on previous MIs and treatment with aspirin or nitrates

REGARDING QT DISPERSION IN ACUTE MYOCARDIAL INFARCTION

Regarding QT dispersion in acute myocardial infarction

Principal factors affecting sudden death risk in myocardial infarction patients

Aim. To assess prognostic value of clinical and functional factors in regard to sudden cardiac death (SCD) risk in patients after myocardial infarction (MI). Material and methods. In total, 420 patients were examined at Day 10-14 after MI; follow-up period lasted for 14 years. General clinical examination, echocardiography, 24-hour electrocardiography (ECG) monitoring, late ventricular potentials (LVP) detection, active orthostatic test (AOT), heart rate variability (HRV) assessment at baseline and during functional tests, as well as psychological testing, were performed. SCD risk was assessed by Cox multi-factor analysis and Kaplan-Meier survival curve method. Results. According to Cox multivariate regression analysis, the most important predictors included the following: LVP, HRV reduction, left ventricular ejection fraction <40%, ventricular arrhythmias, previous MI, and hypotension in AOT. Prognostic accuracy and positive predictive value of this model were high enough to assess SCD risk. Conclusion. To assess SCD risk in MI patients, complex clinical and functional factors - SCD predictors – should be measured

CURRENT METHODS OF ENDOTHELIAL DYSFUNCTION ASSESSMENT AND THEIR POSSIBLE USE IN THE PRACTICAL MEDICINE

A review contains a description of the most common methods of evaluation and monitoring of "endothelial dysfunction" that are assessed in terms of their information content and applicability in the practice of medicine. The term "endothelial function" is interpreted primarily as a function of the regulation of capillary blood flow, carried out by the expense of the dynamic change of the phase of vasoconstriction and vasodilatation in vessels of resistive type (in accordance with the changing needs of cellular metabolism). Assessment of endothelial dysfunction is understood as a generalized indicator of the extent and nature of violations of the regulation of peripheral circulation. It includes an assessment of imbalances between endotheliumdependent vasoconstrictor and vasodilating factors or mismatch of the local and central regulation of capillary blood flow in response to various functional tests or other effects (eg, cold test, or test with local ischemia). All methods of endothelial dysfunction assessment in the survey are divided into invasive and non-invasive. The main feature of invasive methods lies in the direct effect on the endothelium of the coronary or other vessels by introducing into these vessels vasoactive substances such as acetylcholine. Response to the test (vasoconstriction or vasodilation) is evaluated by coronary angiography or by ultrasound. Non-invasive methods of the assessment of endothelial dysfunction or functions of regulation of the peripheral circulation are regarded as the most promising for widespread use. There are two basic methods that underlie functional tests: methods PAT (peripheral arterial tone) and PHG (polyhepatography). Assessment of endothelial dysfunction in many modern scientific researches is important. They are regarded as the causative factors of many different diseases. Such assessments can be useful in everyday medical practice. Assessment of endothelial function provides the clinician with critical information essential for a personalized selection of therapy. In particular, for taking into account the individual characteristics of the local and central regulatory system response of peripheral blood circulation in the various functional tests, or other effects

Clinical and psychological factors affecting sudden death risk in myocardial infarction patients

Aim. To assess prognostic value of clinical and psychological factors in regard to sudden cardiac death (SCD) risk in patients after myocardial infarction (MI). Material and methods. In total, 420 patients were examined at Day 10-14 after MI; follow-up period lasted for 1-4 years. General clinical examination, echocardiography, 24-hour electrocardiography (ECG) monitoring, late ventricular potentials (LVP) detection, active orthostatic test (AOT), heart rate variability (HRV) assessment, psychological testing, if necessary – coronary angiography and endocardial electrophysiological examination were performed. Results. In the first post-MI year, SCD incidence was 6,7%. SCD risk was predicted by anterior MI localization, left ventricular (LV) aneurysm, heart failure, pre-syncope in anamnesis, hypotension during AOT, sinus tachycardia, left bundle block, anxiety and depression symptoms, leukocytosis and monocytosis in acute AMI period, alcohol abuse in anamnesis, treatment features (no beta-adrenoblockers; diuretic therapy). In multivariate analysis, the most important clinical factors included previous MI, hypotension in AOT, LV ejection fraction, ventricular arrhythmias by 24-hour ECG monitoring, HRV and LVP assessment data. Conclusion. Due to high SCD rates in MI patients, SCD risk should be assessed as early as during hospitalization, using relevant clinical and psychological parameters. If needed, detailed examination and secondary SCD prevention measures should be performed