Electroencephalography as a Tool for Assessment of Brain Ischemic Alterations after Open Heart Operations

Cardiac surgery is commonly associated with brain ischemia. Few studies addressed brain electric activity changes after on-pump operations. Eyes closed EEG was performed in 22 patients (mean age: 45.2 ± 11.2) before and two weeks after valve replacement. Spouses of patients were invited to participate as controls. Generalized increase of beta power most prominent in beta-1 band was an unambiguous pathological sign of postoperative cortex dysfunction, probably, manifesting due to gamma-activity slowing (“beta buzz” symptom). Generalized postoperative increase of delta-1 mean frequency along with increase of slow-wave activity in right posterior region may be hypothesized to be a consequence of intraoperative ischemia as well. At the same time, significant changes of alpha activity were observed in both patient and control groups, and, therefore, may be considered as physiological. Unexpectedly, controls showed prominent increase of electric activity in left temporal region whereas patients were deficient in left hemisphere activity in comparison with controls at postoperative followup. Further research is needed in order to determine the true neurological meaning of the EEG findings after on-pump operations

Size of Left Cardiac Chambers Correlates with Cerebral Microembolic Load in Open Heart Operations

Background. Microemboli are a widely recognized etiological factor of cerebral complications in cardiac surgery patients. The present study was aimed to determine if size of left cardiac chambers relates to cerebral microembolic load in open heart operations. Methods. Thirty patients participated in the study. Echocardiography was performed in 2-3 days before surgery. A transcranial Doppler system was used for registering intraoperative microemboli. Results. Preoperative left atrium and left ventricular end-systolic and end-diastolic sizes significantly correlated with intraoperative microembolic load (rs = 0.48, 0.57 and 0.53, Ps < .01, resp.). The associations between left ventricular diameters and number of cerebral microemboli remained significant when cardiopulmonary bypass time was included as a covariate into the analysis. Conclusions. The present results demonstrate that increased size of left heart chambers is an influential risk factor for elevated cerebral microembolic load during open heart operations. Mini-invasive surgery and carbon dioxide insufflation into wound cavity may be considered as neuroprotective approaches in patients with high risk of cerebral microembolism

Perioperative glycemic control in patients with coronary artery disease and diabetes mellitus type 2 undergoing coronary artery bypass grafting: results of pilot study

BACKGROUND: According to different studies, diabetes mellitus type 2 (DM2) is associated with higher mortality after undergoing coronary artery bypass grafting (CABG). Perioperative hyperglycaemia, even in non-DM2 patients, is associated with adverse outcomes after CABG. Thus, successful perioperative blood glucose control (BGC) is mandatory to reduce the risk of death and postoperative complications. Nowadays, the most effective method for BGC in the operating room is still unknown. AIMS: To assess the continuous glucose monitoring (CGM) efficacy in association with insulin pump therapy in patients with coronary artery disease (CAD) and DM2 undergoing CABG in intra- and early postoperative periods. METHODS: The study involved 97 patients undergoing isolated CABG. Patients were divided into two groups: 48 patients with DM2 and 49 patients without DM2. In both groups of patients, we used CGM in intra- and early postoperative periods (72 hours). In some patients with DM2, CGM was associated with insulin pump therapy (MiniMed Paradigm Veo 554/754) to successfully control postoperative glucose level. Besides commonly used tests (such as HbA1C and lipid profile), we analysed high sensitive C-reactive protein (hs-CRP) levels before surgery, and then at 1 hour, 12 hours and 7 days after CABG in order to estimate their prognostic value. RESULTS: During the 48 hours after CABG, there was a trend towards having higher glucose levels in both groups of patients with and without DM2 according to CGM. In patients with DM2, the glucose level was significantly increased (р&lt;0,05). Insulin pump therapy resulted in glycemic control improvement in early follow-up (72 hours). Moreover, there were no hypoglycaemic episodes in patients on insulin pump therapy and also in patients prescribed bolus insulin therapy. We revealed the trend towards lower rate of postpericardiotomy syndrome (PCTS) in patients on insulin pump therapy compared to patients prescribed bolus insulin therapy in the early postoperative period (p=0,1). Hs-CRP level was lower in patients with DM2 who were on insulin pump therapy compared to patients prescribed bolus insulin therapy in the early postoperative period (р&lt;0,05). This most likely confirms that insulin pump therapy decreases systemic inflammatory response. CONCLUSIONS: Thus, we demonstrated the CGM feasibility, safety and efficacy in association with insulin pump therapy in patients with DM2 undergoing CABG

ОБЕСПЕЧЕННОСТЬ ВЫСОКОТЕХНОЛОГИЧНОЙ МЕДИЦИНСКОЙ ПОМОЩЬЮ ПО ПРОФИЛЮ «СЕРДЕЧНО-СОСУДИСТАЯ ХИРУРГИЯ» ЖИТЕЛЕЙ СУБЪЕКТОВ РОССИЙСКОЙ ФЕДЕРАЦИИ В 2021 ГОДУ

Highlights: The article presents data on the availability of various types of high-tech cardiovascular care services to residents of subjects of the Russian Federation. The authors used original methodology based on the data of the Healthcare Administration of the subjects of the Russian Federation. The obtained data were compared with the data from the Federal Tax Service Office No. 12, and 14, demographic and socio-economic indicators of the subjects of the Russian Federation. The results of the analysis open up new opportunities for studying the causes of pronounced differences in the provision of high-tech cardiovascular care to the population of the country's regions and taking appropriate regulatory measures, thus contributing to practical healthcare. Aim. To analyze the provision of high-tech cardiovascular care (HTCC) to residents of the Russian Federation regions in 2021 taking into account social and economic factors.Methods. The data from the original form designed in A.N. Bakulev National Medical Research Center of Cardiovascular Surgery containing information on the number of patients who underwent cardiovascular surgeries were compared with the data from the Federal Tax Service Office follow-up forms No.12 and No.14, taking into account demographic and social-economic factors of the RF regions according to the Federal Service of State Statistics. 74 regions were included into the analysis. The following methods of univariate statistics were used: Spearman’s and Kendall’s rank correlation, measures of central tendency and variance were calculated. Intergroup comparison was carried out using Mann-Whitney two-tailed test and Kruskall-Wallis one-way analysis of variance.Results. The mean provision of HTCC included in the Section I of the Free Health Care Policies for Citizens (HTCC-1) was 1910 surgeries per 1 million population, provision of HTCC included in the Section II (HTCC-2) – was 789.5, respectively. We have noted the negative correlation between the amount of HTCC -1 and HTCC -2 surgeries and hypertension mortality (p = 0.034). The mortality from other acute CAD correlated negatively with the provision of coronary artery bypass grafting (CABG, p = 0.034). The authors also noted the negative correlation between the provision of HTCC -2 surgeries and circulatory diseases (CD) overall incidence (p = 0.032), primary CD incidence (p = 0.014), CAD overall incidence (p = 0.034) and more. The region’s economic development level influenced the provision of HTCC -2 surgeries. The positive correlation coefficients were obtained for per capita income (p = 0.004), median per capita income (p = 0.002), real amount of granted pensions (p = 0.003) and other parameters. The number of CABG per 1 million and life expectancy was higher in the RF regions where CABG was performed locally compared to the regions that did not provide cardiovascular care (205.82 vs 165.55 and 69.49 vs 68.64).Conclusion. The indicators of HTCC-1 and HTCC-2 provision in the RF regions differed by 8.4 and 9.2 times, respectively; the indicators of provision of surgeries by 14.7 and 201.9 times. Providing residents of the RF regions with cardiovascular surgeries is influenced by a number of factors among which we highlight the availability of this type of treatment in the region, regional economic resources to co-finance HTCC -2 treatment, population`s compliance with the surgical treatment safety checklist.Основные положенияВ статье впервые представлены данные об обеспеченности различными видами высокотехнологичной медицинской помощи по профилю «сердечно-сосудистая хирургия» жителей отдельных субъектов РФ. Использована оригинальная методика на основе данных органов управления здравоохранением субъектов РФ. Полученные данные также сопоставлены с данными ФСН № 12, 14, демографическими и социально-экономическими показателями субъектов РФ. Вклад исследования в практическое здравоохранение: результаты проведенного анализа открывают новые возможности для изучения причин выраженных различий в обеспеченности населения регионов страны медицинской помощью по профилю «сердечно-сосудистая хирургия» и принятия соответствующих мер регулирования. РезюмеЦель исследования. Изучить обеспеченность высокотехнологичной медицинской помощью (ВМП) по профилю «сердечно-сосудистая хирургия» (ССХ) жителей субъектов РФ в 2021 г. с учетом социально-экономических особенностей.Материалы и методы. Данные формы, разработанной в ФГБУ «НМИЦ ССХ им. А.Н. Бакулева» Минздрава России, о количестве пациентов, которым выполнены операции по профилю ССХ, сопоставлены со сведениями форм федерального статистического наблюдения № 12 и 14, демографическими и социально-экономическими показателями субъектов РФ по данным Росстата. В анализ включены 74 региона. Использованы методы описательной статистики – рассчитаны показатели центральной тенденции и дисперсии, методы ранговой корреляции Кендалла и Спирмена. Межгрупповые сравнения проведены при помощи критерия Манна – Уитни для двух выборок и однофакторного дисперсионного анализа Краскела – Уоллиса.Результаты. В среднем обеспеченность ВМП раздела I государственной программы бесплатного оказания гражданам медицинской помощи (ВМП-1) составила 1 910 операций на 1 млн населения, ВМП раздела II программы (ВМП-2) – 789,5. Выявлены отрицательные корреляционные связи между суммой операций ВМП-1 и ВМП-2 и смертностью от гипертонической болезни (p = 0,034). Смертность от других форм острой ишемической болезни сердца отрицательно коррелировала с обеспеченностью коронарного шунтирования (p = 0,034). Также определены отрицательные корреляционные связи между обеспеченностью операциями ВМП-2 и общей заболеваемостью патологиями системы кровообращения (p = 0,032), первичной заболеваемостью патологиями системы кровообращения (p = 0,014), общей заболеваемостью ишемической болезнью сердца (p = 0,034) и др. Уровень экономического развития региона ассоциирован с обеспеченностью операциями ВМП-2. Положительные коэффициенты корреляции получены для среднедушевых денежных доходов населения (p = 0,004), медианного среднедушевого денежного дохода населения (p = 0,002), реального размера назначенных пенсий (p = 0,003) и других показателей. Число коронарных шунтирований на 1 млн и ожидаемая продолжительность жизни были выше в субъектах РФ, в которых данные вмешательства проводят на своей территории, по сравнению с теми, где отсутствует кардиохирургия (205,82 против 165,55 и 69,49 против 68,64).Заключение. Показатели обеспеченности населения ВМП-1 и ВМП-2 по профилю ССХ в субъектах РФ различались в 8,4 и 9,2 раза соответственно, а показатели обеспеченности операциями – в 14,7 и 201,9 раза.. Обеспеченность населения регионов РФ операциями по профилю ССХ связана со множеством факторов, среди которых следует выделить доступность данного вида лечения в регионе постоянного проживания, экономические возможности региона в софинансировании лечения в рамках ВМП-2, приверженность населения хирургическому лечению заболеваний

Conformational fingerprint of blood and tissue ACEs: Personalized approach.

BackgroundThe pattern of binding of monoclonal antibodies (mAbs) to 18 epitopes on human angiotensin I-converting enzyme (ACE)-"conformational fingerprint of ACE"-is a sensitive marker of subtle conformational changes of ACE due to mutations, different glycosylation in various cells, the presence of ACE inhibitors and specific effectors, etc.Methodology/principal findingsWe described in detail the methodology of the conformational fingerprinting of human blood and tissue ACEs that allows detecting differences in surface topography of ACE from different tissues, as well detecting inter-individual differences. Besides, we compared the sensitivity of the detection of ACE inhibitors in the patient's plasma using conformational fingerprinting of ACE (with only 2 mAbs to ACE, 1G12 and 9B9) and already accepted kinetic assay and demonstrated that the mAbs-based assay is an order of magnitude more sensitive. This approach is also very effective in detection of known (like bilirubin and lysozyme) and still unknown ACE effectors/inhibitors which nature and set could vary in different tissues or different patients.Conclusions/significancePhenotyping of ACE (and conformational fingerprinting of ACE as a part of this novel approach for characterization of ACE) in individuals really became informative and clinically relevant. Appreciation (and counting on) of inter-individual differences in ACE conformation and accompanying effectors make the application of this approach for future personalized medicine with ACE inhibitors more accurate. This (or similar) methodology can be applied to any enzyme/protein for which there is a number of mAbs to its different epitopes

ACE phenotyping in human heart

<div><p>Aims</p><p>Angiotensin-converting enzyme (ACE), which metabolizes many peptides and plays a key role in blood pressure regulation and vascular remodeling, is expressed as a type-1 membrane glycoprotein on the surface of different cells, including endothelial cells of the heart. We hypothesized that the local conformation and, therefore, the properties of heart ACE could differ from lung ACE due to different microenvironment in these organs.</p><p>Methods and results</p><p>We performed ACE phenotyping (ACE levels, conformation and kinetic characteristics) in the human heart and compared it with that in the lung. ACE activity in heart tissues was 10–15 lower than that in lung. Various ACE effectors, LMW endogenous ACE inhibitors and HMW ACE-binding partners, were shown to be present in both heart and lung tissues. “Conformational fingerprint” of heart ACE (i.e., the pattern of 17 mAbs binding to different epitopes on the ACE surface) significantly differed from that of lung ACE, which reflects differences in the local conformations of these ACEs, likely controlled by different ACE glycosylation in these organs. Substrate specificity and pH-optima of the heart and lung ACEs also differed. Moreover, even within heart the apparent ACE activities, the local ACE conformations, and the content of ACE inhibitors differ in atria and ventricles.</p><p>Conclusions</p><p>Significant differences in the local conformations and kinetic properties of heart and lung ACEs demonstrate tissue specificity of ACE and provide a structural base for the development of mAbs able to distinguish heart and lung ACEs as a potential blood test for predicting atrial fibrillation risk.</p></div

Effect of dilution on ACE activity in the homogenates of heart chambers.

<p>ACE activity and ZPHL/HHL ratio were measured in the homogenates of human heart chambers at different dilutions using two substrates (as in the legend to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0181976#pone.0181976.g001" target="_blank">Fig 1</a>). Data are expressed as absolute values (<b>A</b>-<b>C</b>) and as % from homogenates at maximal dilution—1/30 (<b>D</b>-<b>F</b>). Each value is a mean of several (2–3) experiments on separate homogenates in duplicates.</p

Conformational characteristics of different ACEs.

<p>Conformational fingerprinting of the heart and lung ACEs was performed with a set of 17 mAbs to the two-domain ACE. Immunoprecipitated ACE activity from purified ACEs solutions (<b>A</b>), tissue homogenates from 10 donors (<b>B</b>), or ACEs after perfusion into rat blood circulation (<b>C</b>) are presented as % (“binding ratio”) for heart ACE from that of lung ACE. Ratios increased more than 20% are highlighted in orange, more than 50% in dark orange, and more than 200% in red, while decreased more than 20% are highlighted in yellow and more than 50% in deep blue. Data are mean ± SD of at least 3 experiments (each in duplicates), p<0.01.</p

Effect of dilution on the apparent ACE activity in the heart and lung homogenates.

<p>ACE activity was measured in the heart and lung homogenates from 10 donors at different dilutions using two substrates, ZPHL and HHL (as in the legend to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0181976#pone.0181976.g001" target="_blank">Fig 1</a>). Data are expressed as % from the ACE activity in undiluted homogenates (<b>A,B</b>), as well as % of ZPHL/HHL ratio from that for undiluted homogenates (<b>C</b>,<b>D</b>). Each value is a mean of several (2–3) experiments in duplicates, p<0.01.</p