The Effect of Mechanical Properties of Synthetic Prostheses Made by Electrospinning on the Results of Experimental Implantation in the Infrarenal Abdominal Aorta.

BACKGROUND: The research aims to study the effect of circumferential compliance of synthetic vascular prostheses on their healing during implantation in the infrarenal abdominal aorta of pigs. METHODS: In an experiment, 12 pigs were implanted with blood vessel prostheses in the infrarenal abdominal aorta. The prostheses possessed elastic characteristics obtained by a tensile testing machine, and differed in circumferential compliance: rigid (polycaprolactone [PCL]); less compliant than the native aorta (polyurethane [PU]); comparable in compliance to the native aorta (copolymer of vinylidene fluoride with hexafluoropropylene) before (FKM) and after radiation treatment (FKM-γ). The implanted prostheses compliance was measured by aortography during the first 3 days and 1 month after implantation, the condition of the prosthesis capsule was evaluated by macroscopic preparations and histologic examination. RESULTS: Pulsation on PCL prostheses was nonexistent immediately after implantation. On PU prostheses, slight pulsation was noted during the first 3 days and disappeared after 1 month. On FKM prostheses, although pulsation persisted after 1 month, a significant expansion of prostheses was also recorded as a result of fatigue plastic deformation. On FKM-γ prostheses, pulsation comparable in magnitude with aortic pulsation was present 1 month after implantation with no change in the size of the prosthesis. Macroscopic preparations reveal significant differences in the formed connective tissue capsule. The PCL prosthesis capsule is thick, narrowing the lumen of the vessel from the outside. The outer surface of PU prostheses is covered with a thinner uniform fibrous capsule. The inner surface of the FKM and FKM-γ prostheses is covered with a thin layer of smooth whitish tissue. The FKM prosthesis, unlike the FKM-γ prosthesis, is sharply expanded. In all cases, moderate aortic expansion was observed distal to the prosthesis. According to the histologic data, the outer and inner capsules of PCL prostheses are covered with a thick layer of fibrous tissue with signs of productive inflammation and foci of calcification. PU prostheses are surrounded by a thick connective tissue capsule partially endothelialized from the inside; the outer capsule is randomly populated with fibroblastic cells. FKM prostheses have a thin outer capsule where smooth muscle cells are visible, mainly oriented along and across the prosthesis axis; the inner capsule is thin and completely covered with a layer of endothelial cells from the side of the lumen. A layered structure is visible in the prosthesis capsule of FKM-γ, and the fibroblast cells in each layer of the capsule are oriented along or across the prosthesis axis, similar to the structure of a natural arterial vessel. The inner surface of the prosthesis is completely endothelialized. CONCLUSIONS: The healing and degree of inflammation in a capsule of blood vessel prostheses implanted in the infrarenal abdominal aorta of pigs depend on the degree of their circumferential compliance. Although maintaining pulsations, the cellular structure of the capsule is characterized by a greater degree of differentiation and approaches the structure of the native arterial wall.

Noninvasive Predictors of Malignant Arrhythmias.

BACKGROUND: Prediction and potential prevention of sudden cardiac death (SCD) due to malignant ventricular arrhythmia (MVA) represent an obvious unmet medical need. We estimated the prognostic relevance of numerous biomarkers associated with future MVA development in patients with coronary artery disease (CAD) over 2 years of follow-up. METHODS: Patients with stable documented CAD (n = 97) with a mean age of 61 ± 10 years were prospectively enrolled in a single-center observational cohort study. Heart failure was diagnosed in 68% of the patients (NYHA class II-III). The mean left ventricular ejection fraction (LVEF) was 50 ± 13%, while 20% of patients had LVEF ≤35%. Sixty-two patients underwent myocardial revascularization during the follow-up (mean 25 ± 11 months). Clinical characteristics (age, gender, diabetes, history of coronary disease and arrhythmias, prior interventions and antecedent medications), noninvasive electrophysiological markers [microvolt T-wave alterations, signal-averaged electrocardiography, QT interval duration and alteration, and heart rate turbulence (HRT) and HR variability], laboratory indices [serum creatinine and creatinine clearance, brain natriuretic peptide (BNP), NT-proBNP, and C-reactive protein and troponin T levels] were assessed with regard to the MVA prognosis. RESULTS: MVA was diagnosed in 11 patients during the prospective follow-up. Prior percutaneous coronary intervention (p < 0.05), MVA or syncope (p < 0.05), on-pump coronary artery bypass grafting during follow-up (p < 0.01), LVEF ≤47% (p < 0.01), a left atrium size ≥4.7 cm (p < 0.05), left atrium index (p = 0.01), filtered QRS duration (p < 0.05), abnormal HRT (x03C7;2 = 6.2, p = 0.01) or turbulence slope (x03C7;2 = 9.5, p < 0.01), BNP ≥158 pg/ml (p < 0.01) and NT-proBNP ≥787 pg/ml (x03C7;2 = 4.4, p < 0.05) were significantly associated with MVA risk by univariate analysis. However, only prior MVA or syncope [odds ratio (OR) 11.1; 95% confidence interval (CI) 2.8-44.4; p < 0.01], abnormal HRT (x041E;R 13.6; 95% CI 2.8-66.1; p < 0.01) and plasma BNP (x041E;R 14.3; 95% CI 3.2-65.0; p < 0.01) remained independent predictors of MVA occurrence by multivariate Cox regression analysis. CONCLUSION: Prior syncope or MVA, HRT and elevated plasma BNP were independent MVA predictors, advocating for the prospective screening of high-risk CAD patients for potential SCD awareness.

Repair of complete atrioventricular septal defect in infants with down syndrome: outcomes and long-term results.

In clinical practice, the combination of congenital heart disease (CHD) with malformations of other organs occurs in about 10 % of cases, including chromosomal disease with heart defects, which are observed mainly with certain syndromes. In the Bakoulev SCCS (Moscow, Russian Federation), from 01.2005 to 01.2011, complete atrioventricular septal defect (CAVSD) repair was performed on 163 patients (5.6 ± 3.0 months) with Down Syndrome (DS) using the single-patch (n = 40) and the two-patch (n = 123) methods. The control group consisted of 214 infants aged 6.49 ± 3.03 months with CAVSD and normal karyotype. A retrospective cohort study was made, as well as a comparative analysis of the immediate (up to 30 days) and long-term (12-75 months, at the average of 56 ± 15) results of the repair of CAVSD in infants with DSand normal karyotype/chromosome set (NK). During the hospital treatment period, we registered the following complications: pulmonary hypertensive crises in 6 % (n = 9) of patients with DS and in 10 % (n = 21) of infants with NK, infectious complications in 21% (n = 34) of patients with DS and in 8% (n = 17) of infants with NK. Squeal structures in groups were differentiated. The doses and duration of cardiotonic support in the NK patients were significantly higher in comparison with the DS patients (7.5 ± 2.1 days vs 3.4 ± 1.15 days, p < 0.05). Respiratory infections on the background of immunodeficiency were found more often in the DS group (21% in DS vs 8% in NK, p < 0.05), demanding higher postoperative pulmonary ventilation time in DS patients in comparison with normal infants was required (DS 5.1 ± 2.8 days vs NK 1.7 ± 0.8 days, p < 0.05). In DS infants, abnormalities of the left AV valve (doubling of the mitral valve, single papillary muscle, closely spaced groups of papillary muscles, leaflet or chordal dysplasia, hypoplastic valve ring) occur as statistically significant (8% DS vs 12% NK; p < 0.05) which is rarer than in children having the same defect, but without Down syndrome. Concerning the long-term results, there was no significant difference (Gehan-Wilcoxon test) in actuarial freedom from reoperation after repair of CAVSD between DS and NK groups (p < 0.13). However, the presence of Down Syndrome in patients significantly increases the risk of severe co-morbidities that have a significant impact on the recovery period, as well as on life expectancy even after successful CHD correction.

Dynamics of factor XIII levels after open heart surgery for congenital heart defects: do cyanotic and acyanotic patients differ?

Cardiopulmonary bypass (CPB) reduces coagulation factor levels through hemodilution and consumption. Differences in CPB-induced alterations of factor XIII (FXIII) levels in children with cyanotic and acyanotic congenital heart defects (CHDs) are not well characterized. FXIII activity (determined by Berichrom assay), prothrombin index, activated partial thromboplastin time, and fibrinogen were measured before open heart surgery with CPB and 5 days postoperatively for children older than 3 years with acyanotic (n = 30) and cyanotic (n = 30) CHDs. The preoperative FXIII levels did not differ significantly among the children of the compared groups. The cyanotic patients showed a significantly longer duration of CPB (111.4 ± 45.8 vs 71.5 ± 33.6 min; p = 0.026) and aortic cross-clamp (68.0 ± 27.1 vs 45.4 ± 31.4 min; p = 0.034). The drop in FXIII levels after termination of CPB was more profound for the children with cyanotic CHDs (87.1 ± 13.4 to 49.1 ± 13.2 vs 81.5 ± 12.6 to 58.6 ± 11.1 %, respectively; p = 0.018). The cyanotc patients also were restored to their baseline FXIII levels later than the children with acyanotic CHDs (at 48 vs 24 h). The post-CPB dynamics of the majority of the other coagulation parameters in the compared groups of patients were similar. The cyanotic patients experienced significantly greater postoperative blood loss than the acyanotic patients (12.6 ± 4.9 vs 5.0 ± 2.1 mL/kg; p < 0.001) and were transfused with larger volumes of red blood cells (10.4 ± 6.5 vs 4.2 ± 2.5 mL/kg; p = 0.007). The decrease in FXIII levels after CPB is more profound and lasts longer in children with cyanotic CHDs than in acyanotic patients. The rational strategy of postoperative FXIII replacement therapy for these categories of patients needs to be determined.

Endometrial regenerative cells for treatment of heart failure: a new stem cell enters the clinic.

Heart failure is one of the key causes of morbidity and mortality world-wide. The recent findings that regeneration is possible in the heart have made stem cell therapeutics the Holy Grail of modern cardiovascular medicine. The success of cardiac regenerative therapies hinges on the combination of an effective allogeneic "off the shelf" cell product with a practical delivery system. In 2007 Medistem discovered the Endometrial Regenerative Cell (ERC), a new mesenchymal-like stem cell. Medistem and subsequently independent groups have demonstrated that ERC are superior to bone marrow mesenchymal stem cells (MSC), the most widely used stem cell source in development. ERC possess robust expansion capability (one donor can generate 20,000 patients doses), key growth factor production and high levels of angiogenic activity. ERC have been published in the peer reviewed literature to be significantly more effect at treating animal models of heart failure (Hida et al. Stem Cells 2008).Current methods of delivering stem cells into the heart suffer several limitations in addition to poor delivery efficiency. Surgical methods are highly invasive, and the classical catheter based techniques are limited by need for sophisticated cardiac mapping systems and risk of myocardial perforation. Medistem together with Dr. Amit Patel Director of Clinical Regenerative Medicine at University of Utah have developed a novel minimally invasive delivery method that has been demonstrated safe and effective for delivery of stem cells (Tuma et al. J Transl Med 2012). Medistem is evaluating the combination of ERC, together with our retrograde delivery procedure in a 60 heart failure patient, double blind, placebo controlled phase II trial. To date 17 patients have been dosed and preliminary analysis by the Data Safety Monitoring Board has allowed for trial continuation.The combined use of a novel "off the shelf" cell together with a minimally invasive 30 minute delivery method provides a potentially paradigm-shifting approach to cardiac regenerative therapy.

Results of coronary artery bypass grafting in myocardial bridging of left anterior descending artery.

BACKGROUND: We aimed to evaluate the graft patency rate following coronary artery bypass grafting (CABG) to the left anterior descending artery (LAD) with proximal myocardial bridging (MB). While MB is generally a benign coronary abnormality, ischemia, stunning, and sudden death have been reported. In symptomatic patients with proximal LAD systolic compression of >50%, positive for ischemic noninvasive testing and noneffective optimal medical therapy, coronary intervention could be indicated. Few studies of CABG in myocardial bridging have been reported. The influence of high flow in coronaries with MB on graft patency is cause for concern. METHODS: We retrospectively studied 39 patients operated on for isolated MB of proximal LAD with >50% systolic compression. All patients were severely symptomatic despite optimal medical therapy and positive noninvasive tests for myocardial ischemia. CABG was performed through the midsternotomy with cardiopulmonary bypass and cardioplegia. Patients were divided into two groups: in 20 patients, LAD was bypassed with left internal mammary artery (LIMA) (Group 1) and in 19 patients with saphenous vein graft (SVG) (Group 2). All patients underwent follow-up coronary angiography. RESULTS: Demographics and degree of systolic compression of the LAD were similar in both groups. There was no mortality or major morbidity. Freedom from angina was 68% in Group 1 and 94% in Group 2 at 18 months postoperatively (p = 0.58). Twelve LIMA grafts and three SVGs were found occluded (p = 0.002). CONCLUSIONS: LIMA patency in myocardial bridging of the LAD can be low. SVGs should be considered in cases of CABG for myocardial bridging.

The Role of «Novel¼ Biomarkers of Systemic Inflammation in the Development of Early Hospital Events after Aortic Valve Replacement in Patients with Aortic Stenosis.

INTRODUCTION: The pathogenesis of aortic stenosis includes the processes of chronic inflammation, calcification, lipid metabolism disorders, and congenital structural changes. The goal of our study was to determine the predictive value of novel biomarkers of systemic inflammation and some hematological indices based on the numbers of leukocytes and their subtypes in the development of early hospital medical conditions after mechanical aortic valve replacement in patients with aortic stenosis. MATERIALS AND METHODS: This was a cohort study involving 363 patients who underwent surgical intervention for aortic valve pathology between 2014 and 2020. The following markers of systemic inflammation and hematological indices were studied: SIRI (Systemic Inflammation Response Index), SII (Systemic Inflammation Index), AISI (Aggregate Index of Systemic Inflammation), NLR (Neutrophil/Lymphocyte Ratio), PLR (Platelet/Lymphocyte Ratio), and MLR (Monocyte/Lymphocyte Ratio). Associations of the levels of these biomarkers and indices with the development of in-hospital death, acute kidney injury, postoperative atrial fibrillation, stroke/acute cerebrovascular accident, and bleeding were calculated. RESULTS: According to an ROC analysis, an SIRI > 1.5 (p < 0.001), an SII > 718 (p = 0.002), an AISI > 593 (p < 0.001), an NLR > 2.48 (p < 0.001), a PLR > 132 (p = 0.004), and an MLR > 0.332 (p < 0.001) were statistically significantly associated with in-hospital death. Additionally, an SIRI > 1.5 (p < 0.001), an NLR > 2.8 (p < 0.001), and an MLR > 0.392 (p < 0.001) were associated with bleeding in the postoperative period. In a univariate logistic regression, SIRI, SII, AISI, and NLR were statistically significant independent factors associated with in-hospital death. In a multivariate logistic regression model, SIRI was the most powerful marker of systemic inflammation. CONCLUSION: SIRI, SII, AISI, and NLR as novel biomarkers of systemic inflammation were associated with in-hospital mortality. Of all markers and indices of systemic inflammation in our study, SIRI was the strongest predictor of a poor outcome in the multivariate regression model.

Microwave Near-Field Dynamical Tomography of Thorax at Pulmonary and Cardiovascular Activity.

The developed near-field microwave diagnostics of dynamical lung tomography provide information about variations of air and blood content depth structure in the processes of breathing and heart beating that are unattainable for other available methods. The method of dynamical pulse 1D tomography (profiling) is based on solving the corresponding nonlinear ill-posed inverse problem in the extremely complicated case of the strongly absorbing frequency-dispersive layered medium with the dual regularization method-a new Lagrange approach in the theory of ill-posed problems. This method has been realized experimentally by data of bistatic measurements with two electrically small bow-tie antennas that provide a subwavelength resolution. The proposed methods of 3D lung tomography based on the multisensory pulse, multifrequency, or multi-base measurements are based on solving the corresponding integral equations in the Born approximation. The experimental 3D tomography of lung air content was obtained by the results of the multiple 1D pulse profiling by pulse measurements in several grid points over the planar square region of the thorax. Additionally, the possible applicability of multifrequency measurements of scattered harmonic signals in the monitoring of lungs was demonstrated by four-frequency measurements in the process of breathing. The results demonstrated the feasibility of the proposed control in the diagnosis of some lung diseases.

Predictors of Mortality Following Aortic Valve Replacement in Aortic Stenosis Patients.

Background: Understanding of the risk factors for the development of adverse outcomes after aortic valve replacement is necessary to develop timely preventive measures and to improve the results of surgical treatment. Methods: We analyzed patients with aortic stenosis (n = 742) who underwent surgical treatment in the period 2014−2020. The average age was 63 (57;69) years­men 58%, women 42%. Results: The hospital mortality rate was 3% (22 patients). The following statistically significant threshold values (cut-off points) were obtained in the ROC analysis: aortic cross-clamp time > 93 min AUC (CI) 0.676 (0.640−0.710), p = 0.010; cardiopulmonary bypass time > 144 min AUC (CI) 0.809 (0.778−0.837), p < 0.0001, hemoglobin before op <120 g/L. AUC (CI) 0.762 (0.728−0.793), p < 0.0001, hematocrit before op <39% AUC (CI) 0.755 (0.721−0.786), p < 0.001, end-diastolic dimension index >2.39 AUC (CI) 0.647 (0.607−0.686), p = 0.014, end-systolic dimension index > 1.68 AUC (CI) 0.657 (0.617−0.695), p = 0.009. Statistically significant independent predictors of hospital mortality were identified: BMI > 30 kg/m2 (OR 2.84; CI 1.15−7.01), ischemic heart disease (OR 3.65; CI 1.01−13.2), diabetes (OR 3.88; CI 1.38−10.9), frequent ventricular ectopy before operation (OR 9.78; CI 1.91−50.2), mitral valve repair (OR 4.47; CI 1.76−11.3), tricuspid valve repair (OR 3.06; CI 1.09−8.58), 3 and more procedures (OR 4.44; CI 1.67−11.8). Conclusions: The hospital mortality rate was 3%. The main indicators associated with the risk of death were: diabetes, overweight (body mass index more than 30 kg/m2), frequent ventricular ectopy before surgery, hemoglobin level below 120 g/L, hematocrit level below 39%, longer cardiopulmonary bypass time and aortic cross-clamp time, additional mitral and tricuspid valve interventions.

Colchicine for Prevention of Atrial Fibrillation after Cardiac Surgery in the Early Postoperative Period.

BACKGROUND: Postoperative atrial fibrillation (POAF) is a common complication of cardiac surgery. It has been proven to be associated with an increase in the incidence of early complications and mortality, an increase in the rate of hospital stay duration, and economic costs of their treatment. One of the pharmaceutical drugs recommended by the American College of Cardiology (ACC)/American Heart Association (AHA) for preventing POAF is colchicine (class IIB). However, the results of research on the efficacy and safety of colchicine are ambiguous and, consequently, require further study. OBJECTIVE: Evaluating the efficacy of short-term colchicine administration in the prevention of POAF in patients after open-heart surgery. MATERIALS AND METHODS: Double-blind, randomized, placebo-controlled clinical trial. The subjects were randomly assigned to two groups: treatment group (n = 50) with subjects receiving 1 mg of colchicine 24 h before the surgery, as well as on days 2, 3, 4, and 5 in the postoperative period; and the control group (n = 51), receiving placebo on the same schedule. The primary endpoint was the frequency of POAF in both groups within 7 days after surgery. RESULTS: The study included 101 patients (82 men, 19 women). Baseline clinical, laboratory, instrumental, and intraoperative data did not differ statistically significantly between the groups. POAF was detected in 9 patients (18%) of the treatment group and 15 subjects (29.4%) of the control group, which had no statistical significance (odds ratio, OR 0.527; 95% Cl 0.206-1.349; p = 0.178). No statistically significant differences were revealed for most secondary endpoints, as well as between the groups for all laboratory parameters. There were statistically significant differences between the groups solely in the frequency of diarrhea: 16 (32%) patients in the treatment group and 6 (11.8%) subjects in the control group (OR 3.529; 95% Cl 1.249-9.972; p = 0.010). CONCLUSIONS: We did not detect any statistical differences between the groups in terms of primary endpoints, which could be due to the insufficient volume of the sample of the study. However, we detected some trends of statistical differences among the groups in terms of some parameters. CLINICALTRIALS: Unique identifier: NCT04224545.

Long-Term Preoperative Atorvastatin or Rosuvastatin Use in Adult Patients before CABG Does Not Increase Incidence of Postoperative Acute Kidney Injury: A Propensity Score-Matched Analysis.

BACKGROUND: Acute kidney injury (AKI) is among the expected complications of cardiac surgery. Statins with pleiotropic anti-inflammatory and antioxidant effects may be effective in the prevention of AKI. However, the results of studies on the efficacy and safety of statins are varied and require further study. METHODS: We conducted a retrospective cohort study to evaluate long-term preoperative intake of atorvastatin and rosuvastatin on the incidence of AKI, based on the "Kidney Disease: Improving Global Outcomes" (KDIGO) criteria in the early postoperative period after coronary artery bypass graft surgery (CABG). We performed propensity score matching to compare the findings in our study groups. The incidence of AKI was assessed on day 2 and day 4 after the surgery. RESULTS: The analysis included 958 patients after CABG. After 1:1 individual matching, based on propensity score, the incidence of AKI was comparable both on day 2 after the surgery (7.4%) between the atorvastatin group and rosuvastatin group (6.5%) (OR: 1.182; 95%Cl 0.411-3.397; p = 0.794), and on postoperative day 4 between the atorvastatin group (3.7%) and the rosuvastatin group (4.6%) (OR: 0.723, 95%Cl 0.187-2.792; p = 0.739). Additionally, there were no statistically significant differences in terms of incidence of AKI after 1:1 individual matching, based on propensity score, between the rosuvastatin group and the control group both on postoperative day 2 (OR: 0.692; 95%Cl 0.252-1.899; p = 0.611) and day 4 (OR: 1.245; 95%Cl 0.525-2.953; p = 0.619); as well as between the atorvastatin group and the control group both on postoperative day 2 (OR: 0.549; 95%Cl 0.208-1.453; p = 0.240) and day 4 (OR: 0.580; 95%Cl 0.135-2.501; p = 0.497). CONCLUSION: Long-term statin use before CABG did not increase the incidence of postoperative AKI. Further, we revealed no difference in the incidence of post-CABG AKI between the atorvastatin and rosuvastatin groups.

Colchicine in Cardiac Surgery: The COCS Randomized Clinical Trial.

BACKGROUND: In patients who underwent cardiac surgery, first-time postoperative atrial fibrillation (POAF) is associated with increased incidence of hospital-acquired complications and mortality. Systemic inflammation is one of confirmed triggers of its development. The anti-inflammatory properties of colchicine can be effective for the POAF prevention. However, the results of several studies were questionable and required further investigation. Hence, we aimed to evaluate the effectiveness of low-dose short-term colchicine administration for POAF prevention in patients after the open-heart surgery. This double-blind randomized placebo-controlled trial included 267 patients, but 27 of them dropped out in the course of the study. Study subjects received the test drug on the day before the surgery and on postoperative days 2, 3, 4 and 5. The rhythm control was conducted immediately after the operation and until the discharge from the hospital. The final analysis included 240 study subjects: 113 in the colchicine group and 127 in the placebo group. POAF was observed in 21 (18.6%) patients of the colchicine group vs. 39 (30.7%) control patients (OR 0.515; 95% Cl 0.281-0.943; p = 0.029). We observed no statistically significant differences between the patient groups in the secondary endpoints of the study (hospital mortality, respiratory failure, stroke, bleeding, etc.). For other parameters characterizing the severity of inflammation (pericardial effusion, pleural effusion, WBC count, neutrophil count), there were statistically significant differences between the groups in the early postoperative period (days 3 and 5). Also, statistically significant differences between the groups in the frequency of adverse events were revealed: the incidence of diarrhea in the colchicine group was 25.7% vs. 11.8% in the placebo group (OR 2.578; 95% Cl 1.300-5.111; p = 0.005); for abdominal pain, incidence values were 7% vs. 1.6%, correspondingly (OR 4.762; 95% Cl 1.010-22.91; p = 0.028). Thus, there were statistically significant differences between groups in the primary endpoint, thereby confirming the effectiveness of short-term colchicine use for the POAF prevention after coronary artery bypass grafting and/or aortic valve replacement. Also, we detected statistically significant differences between groups in the frequency of side effects to colchicine: diarrhea and abdominal pain were more common in the colchicine group. This clinical trial is registered with ClinicalTrials database under a unique identifier: NCT04224545.

Accelerated Growth, Differentiation, and Ploidy with Reduced Proliferation of Right Ventricular Cardiomyocytes in Children with Congenital Heart Defect Tetralogy of Fallot.

The myocardium of children with tetralogy of Fallot (TF) undergoes hemodynamic overload and hypoxemia immediately after birth. Comparative analysis of changes in the ploidy and morphology of the right ventricular cardiomyocytes in children with TF in the first years of life demonstrated their significant increase compared with the control group. In children with TF, there was a predominantly diffuse distribution of Connexin43-containing gap junctions over the cardiomyocytes sarcolemma, which redistributed into the intercalated discs as cardiomyocytes differentiation increased. The number of Ki67-positive cardiomyocytes varied greatly and amounted to 7.0-1025.5/106 cardiomyocytes and also were decreased with increased myocytes differentiation. Ultrastructural signs of immaturity and proliferative activity of cardiomyocytes in children with TF were demonstrated. The proportion of interstitial tissue did not differ significantly from the control group. The myocardium of children with TF under six months of age was most sensitive to hypoxemia, it was manifested by a delay in the intercalated discs and myofibril assembly and the appearance of ultrastructural signs of dystrophic changes in the cardiomyocytes. Thus, the acceleration of ontogenetic growth and differentiation of the cardiomyocytes, but not the reactivation of their proliferation, was an adaptation of the immature myocardium of children with TF to hemodynamic overload and hypoxemia.

Local Use of Hydrogel with Amiodarone in Cardiac Surgery: Experiment and Translation to the Clinic.

The objective of this study was to study the use of the hydrogel biopolymer based on sodium alginate ("Colegel") with a drug substance-amiodarone-for the prevention of postoperative atrial fibrillation (POAF) in cardiac surgery. The experimental part of the study was performed on 46 rabbits. Five groups were formed: in the first group, the dose of amiodarone in hydrogel was 1 mg; in the second group-3 mg; in the third group-6 mg; in the fourth group, hydrogel was used without amiodarone; in the fifth group, 60 mg amiodarone was administered intravenously. The animals from each group were removed from the experiment for the pathomorphological study of the heart after 3, 7 and 14 days. The studied endpoints were: the heart rate control; the development of the blockades of the conduction system of the heart; and the development of inflammation according to laboratory pathomorphological studies. The translational clinical part involved a randomized clinical trial which included 60 patients, with an average age of 62 ± 8.5 years. All patients were randomized into two groups: the study group (n = 30, with the application of amiodarone hydrogel) and the control group (n = 30, without the application of amiodarone hydrogel). The dose of amiodarone in the hydrogel material was 60 mg for all patients. The heart rhythm was monitored during 5 days. The primary endpoint was the development of POAF. Secondary endpoints were: the dynamics of heart rate; the duration of the QT and PQ intervals; the development of blockades of the cardiac conduction system; as well as the dynamics of AST and ALT. According to the results of the experimental part, it was found that the method of the local epicardial delivery of amiodarone by the hydrogel material was safe. Hydrogel with amiodarone is effective for reducing the heart rate in the animal experiment in comparison to the control group and the group with the intravenous administration of the drug. The optimal dose of amiodarone in hydrogel was 1 mg per 1 kg. According to the results of the clinical part, it was found that the method of the local epicardial delivery of amiodarone as a hydrogel material proved its safety. Hydrogel with amiodarone at a dose of 60 mg was effective in preventing POAF in patients after coronary artery bypass grafting (CABG) operations in comparison to the control group (p < 0.001). The age and procedure of application of the amiodarone gel were significantly associated with POAF (p = 0.009 and p = 0.011, respectively). The use of hydrogel with amiodarone reduced the probability of developing POAF 18.9-fold. The method of the local epicardial delivery of amiodarone in the form of a hydrogel material is safe. The use of hydrogel with amiodarone after CABG reduced the probability of developing POAF.

Total cavopulmonary connection with a new restorative vascular graft: results at 2 years.

BACKGROUND: To present a 2-year follow-up regarding safety and hemodynamic performance of a new restorative vascular graft used as extracardiac cavo-pulmonary connection in patients with univentricular congenital heart malformations. METHODS: The graft was implanted in five patients (aged 4-12 years) as extracardiac connection between the inferior vena cava and the pulmonary artery. The conduit consists of a bioabsorbable polymer-based implant able to generate endogenous tissue restoration leading to a fully functional neo-vessel while the polymer progressively absorbs. All patients have reached more than 24 months following surgery and underwent echocardiography and magnetic resonance imaging. RESULTS: All patients are doing well at 24 months follow-up, with no graft-related serious adverse events. Transthoracic echocardiography demonstrated adequate function of the conduit in all patients while magnetic resonance imaging showed anatomical and functional stability of the restorative grafts. CONCLUSIONS: The new restorative conduit has been successfully used for the second step of the Fontan procedure as extracardiac total cavopulmonary connection. The results are promising because they suggest that complete transformation of a bioabsorbable polymer and replacement through endogenous tissue may represent a major advantage in the treatment of congenital heart disease patients. Further monitoring will allow to evaluate the long-term behavior of this new graft, in terms of clinical and hemodynamic performance, thrombogenicity and ability to grow.

Oral geranylgeranylacetone treatment increases heat shock protein expression in human atrial tissue.

BACKGROUND: Heat shock proteins (HSPs) are important chaperones that regulate the maintenance of healthy protein quality control in the cell. Impairment of HSPs is associated with aging-related neurodegenerative and cardiac diseases. Geranylgeranylacetone (GGA) is a compound well known to increase HSPs through activation of heat shock factor-1 (HSF1). GGA increases HSPs in various tissues, but whether GGA can increase HSP expression in human heart tissue is unknown. OBJECTIVE: The purpose of this study was to test whether oral GGA treatment increases HSP expression in the atrial appendages of patients undergoing cardiac surgery. METHODS: HSPB1, HSPA1, HSPD1, HSPA5, HSF1, and phosphorylated HSF1 levels were measured by western blot analysis in right and left atrial appendages (RAAs and LAAs, respectively) collected from patients undergoing coronary artery bypass grafting (CABG) who were treated with placebo (n = 13) or GGA 400 mg/da(n = 13) 3 days before surgery. Myofilament fractions were isolated from LAAs to determine the levels of HSPB1 and HSPA1 present in these fractions. RESULTS: GGA treatment significantly increased HSPB1 and HSPA1 expression levels in RAA and LAA compared to the placebo group, whereas HSF1, phosphorylated HSF1, HSPD1, and HSPA5 were unchanged. In addition, GGA treatment significantly enhanced HSPB1 levels at the myofilaments compared to placebo. CONCLUSION: Three days of GGA treatment is associated with higher HSPB1 and HSPA1 expression levels in RAA and LAA of patients undergoing CABG surgery and higher HSPB1 levels at the myofilaments. These findings pave the way to study the role of GGA as a protective compound against other cardiac diseases, including postoperative atrial fibrillation.

Therapeutic value of muscular counterpulsation after coronary bypass grafting operation.

OBJECTIVE: Coronary artery bypass grafting continues to be the operation of choice in patients with severe multiple coronary artery disease. However, there are several unresolved issues such as treatment of postoperative heart failure following bypass surgery. There is worldwide interest in evaluating new treatment methods for this condition. The objective is to determine the effect of a new external, bioassisted circulation-muscular counterpulsation (MCP) method in patients with ischemic heart disease (IHD) undergoing coronary artery bypass grafting (CABG). METHODS: Fifty patients (age 54 +/- 8) undergoing CABG were included in the present analysis. Patients were randomized into two groups: A control group (n = 20) receiving standard postoperative treatment without counterpulsation and a treatment group (n = 30) undergoing MCP with a cardio-synchronized pulse generator using stimulation electrodes on the lower extremities. Treatment was 30 minutes daily for the eight initial postoperative days in addition to standard therapy. In all patients, a resting electrocardiogram (ECG), two-dimensional echocardiography, and impedance plethysmography of the forearm were carried out pre-CABG and on the eighth postoperative day. RESULTS: Follow-up was completed in 94% of the patients. Two patients of the control and one of the treatment group refused follow-up examination. MCP treatment resulted in a 36% decrease of systemic vascular resistance (p < 0.001) compared to a 16% decrease (p = 0.011) in the control group. Postoperative complications occurred in one (3%) patient of the treatment group and in seven (39%) patients of the control group. Compared to the control group, patients in the treatment group had a 28% shorter postoperative hospital stay (12.0 +/- 4.6 days) than in the control group (16.8 +/- 4.4 days) (p < 0.001). CONCLUSIONS: MCP represents a new, noninvasive, ECG-triggered circulation support system, which is effective for achieving hemodynamic improvement via afterload reduction. The use of MCP decreases postoperative complications and significantly shortens the hospital stay.

Advances in Hemodynamic Analysis in Cardiovascular Diseases Investigation of Energetic Characteristics of Adult and Pediatric Sputnik Left Ventricular Assist Devices during Mock Circulation Support.

The need to simulate the operating conditions of the human body is a key factor in every study and engineering process of a bioengineering device developed for implantation. In the present paper, we describe in detail the interaction between the left ventricle (LV) and our Sputnik left ventricular assist devices (LVADs). This research aims to evaluate the influence of different rotary blood pumps (RBPs) on the LV depending on the degree of heart failure (HF), in order to investigate energetic characteristics of the LV-LVAD interaction and to estimate main parameters of left ventricular unloading. We investigate energetic characteristics of adult Sputnik 1 and Sputnik 2 LVADs connected to a hybrid adult mock circulation (HAMC) and also for the Sputnik pediatric rotary blood pump (PRBP) connected to a pediatric mock circulation (PMC). A major improvement of the LV unloading is observed during all simulations for each particular heart failure state when connected to the LVAD, with sequential pump speed increased within 5000-10000 rpm for adult LVADs and 6000-13000 rpm for PRBP with 200 rpm step. Additionally, it was found that depending on the degree of heart failure, LVADs influence the LV in different ways and a significant support level cannot be achieved without the aortic valve closure. Furthermore, this study expands the information on LV-LVAD interaction, which leads to the optimization of the RBP speed rate control in clinics for adult and pediatric patients suffering from heart failure. Finally, we show that the implementation of control algorithms using the modulation of the RBP speed in order to open the aortic valve and unload the LV more efficiently is necessary and will be content of further research.

Surgical treatment of hypertrophic obstructive cardiomyopathy in pediatric patients with severe hypertrophy.

We have undertaken a study over a period of 5 years on 35 hypertrophic obstructive cardiomyopathy (HOCM) patients with severe hypertrophy in the age range between 8 and 15 years. The indication for surgery was based on the diagnosis of severe myocardial hypertrophy in association with serious cardiac failure (New York Heart Association class III or IV) or elevated intraventricular pressure gradients refractory to medical therapy. Furthermore, patients were considered for operation if they met a history of sudden death within their families. A new technique of HOCM surgical correction in pediatric patients with severe hypertrophy was proposed. Conceptually, this approach offers a number of advantages: it affords the excision of the asymmetrically hypertrophied area of the ventricular septum without penetration into the left ventricle cavity; it avoids mechanical damage to the heart conduction system and aortic valve; and for the surgeon, it improves visual inspection of the area to be resected. Here, we describe the disease history of 35 patients, their diagnostic evaluations, the surgical procedure, and the postoperational observations as well as the results of follow-up assessments. We state that the surgery was successful in all 35 cases. There were no early or late deaths. Acute postoperative pericarditis developed in three patients early after surgery. The follow-up period was 38 +/- 7 months, and complications were not observed so far.

Additional superior vena cava combined with abnormal inflow of the hepatic vein.

We represent a case of successful surgical treatment of a rare congenital heart disease: abnormal inflow of an additional superior vena cava into the left atrium, combined with atrial septal defect, mitral and tricuspid valve regurgitation, and abnormal inflow of the left hepatic vein into a roofless coronary sinus.