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Magnesium-sensitive transient receptor potential melastatin (TRPM) ion channels, TRPM6 and TRPM7, are present in several organs, but their roles in the heart remain unclear. Therefore, here, we studied the expression patterns of TRPM6 and TRPM7 in normal and diseased myocardium. Cardiac atrial tissue and cardiomyocytes were obtained from healthy pigs and undiseased human hearts as well as from hearts of patients with ischemic heart disease (IHD) or atrial fibrillation (AF). Immunofluorescence and ELISA were used to detect TRP proteins. TRPM6 and TRPM7 immunofluorescence signals, localized at/near the cell surface or intracellularly, were detected in pig and human atrial tissues. The TRP channel modulators carvacrol (CAR, 100 µM) or 2-aminoethoxydiphenyl borate (2-APB, 500 µM) decreased the TRPM7 signal, but enhanced that of TRPM6. At a higher concentration (2 mM), 2-APB enhanced the signals of both proteins. TRPM6 and TRPM7 immunofluorescence signals and protein concentrations were increased in atrial cells and tissues from IHD or AF patients. TRPM6 and TRPM7 proteins were both detected in cardiac atrial tissue, with relatively similar subcellular localization, but distinctive drug sensitivity profiles. Their upregulated expression in IHD and AF suggests a possible role of the channels in cardiac atrial disease. ispartof: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES vol:23 issue:23 ispartof: location:Switzerland status: published

Straipsnyje apžvelgiami dviburio aortos vožtuvo (DAV) etiologiniai veiksniai, diagnostikos ir chirurginio gydymo galimybės. Naujausios mokslinės literatūros paieška atlikta PubMed ir UpToDate mokslinėse duomenų bazėse. Į sisteminę apžvalgą įtraukta 30 straipsnių nagrinėjama tema. Tyrimo rezultatai atskleidė, kad DAV yra viena dažniausių įgimtų širdies ydų, kuri gali būti izoliuota patologija arba kartu su kitomis įgimtomis kardiovaskulinės sistemos ydomis bei genetiniais sindromais. DAV morfologija yra hemodinamiškai svarbi, nes lemia turbulencinės kraujo tėkmės per vožtuvą atsiradimą ir sukelia struktūrinius (histologinius) pokyčius aortos sienelėje. Ilgą laiką funkciškai normalus DAV simptomų nesukelia, tačiau ilgainiui gali susiformuoti restrikcinis aortos vožtuvo (AV) burių pažeidimas – stenozė ar nesandarumas, kartu su aortos šaknies pažaida, reikalaujančia chirurginio gydymo. Pirmaeilis tyrimas DAV morfologijai nustatyti yra dvimatis (2D) echokardiografinis ištyrimas per krūtinės ląstą. Šiuolaikinėje klinikinėje praktikoje didesnis dėmesys skiriamas AV išsaugančioms operacijoms, esant AV nesandarumui bei DAV morfologijai dėl mažesnių su vožtuvais susijusių komplikacijų ir geresnio išgyvenamumo rodiklių, nesant viso gyvenimo trukmės terapijos antikoaguliantais poreikio.

The expression of the channels-enzymes TRPM6 and TRPM7 in the human heart remains poorly defined, and TRPM6 is generally considered not to be expressed in cardiomyocytes. We examined their expression at protein and mRNA levels using right atrial samples resected from patients (n = 72) with or without ischemic heart disease (IHD) and samples from all chamber walls of explanted human hearts (n = 9). TRPM6 and TRPM7 proteins were detected using immunofluorescence on isolated cardiomyocytes, ELISA on tissue homogenates, and immunostaining of cardiac tissue, whereas their mRNAs were detected by RT-qPCR. Both TRPM6 and TRPM7 were present in all chamber walls, with TRPM7 being more abundant. TRPM6 was co-expressed with TRPM7. The expression levels were dependent on cell incubation conditions (presence or absence of divalent cations, pH of the extracellular milieu, presence of TRP channel inhibitors 2-aminoethoxydiphenyl-borate and carvacrol). These drugs reduced TRPM7 immunofluorescence but increased that of TRPM6. TRPM6 and TRPM7 expression was increased in tissues from IHD patients. This is the first demonstration of the presence and co-expression of TRPM6 and TRPM7 in cardiomyocytes from all chamber walls of the human heart. The increased TRPM6 and TRPM7 expression in IHD suggests that the chanzymes are involved in the pathophysiology of the disease. ispartof: SCIENTIFIC REPORTS vol:11 issue:1 ispartof: location:England status: published

Introduction:To evaluate early and long-term clinical outcomes following aortic valve sparing aortic root reimplantation surgery in patients with leaking bicuspid and tricuspid aortic valves.Methods:The study consisted of 92 consecutive adult patients (tricuspid aortic valve group = 63 and bicuspid aortic valve group = 29) who underwent aortic valve sparing aortic root reimplantation surgery with or without aortic cusp repair for dilatation of the aortic root and/or aortic valve regurgitation at our institution from April 2004 to October 2016. Clinical outcomes were investigated using Kaplan–Meier and log-rank tests between groups.Results:The follow-up was 100% complete with a mean time of 5.3 ± 3.3 years. The 30-day in-hospital mortality was 3.1% in tricuspid aortic valve group and 3.4% in bicuspid aortic valve group patients. The overall survival rates at 10 years did not differ between bicuspid aortic valve and tricuspid aortic valve patient groups (96.6 ± 3.3% vs. 90.3 ± 4.2%, p = 0.3). Freedom from recurrent aortic valve regurgitation (>2+) at 10 years was 90.5 ± 4.1% in tricuspid aortic valve group and 75.7 ± 8.7% in bicuspid aortic valve group (p = 0.06). Freedom from aortic valve reoperation at 10 years was 100% in tricuspid aortic valve group and 83.9 ± 7.4% in bicuspid aortic valve group (p = 0.002).Conclusion:Aortic valve sparing aortic root reimplantation surgery is a safe and efficient technique, providing acceptable long-term survival with low rates of valve-related complications in both tricuspid aortic valve and bicuspid aortic valve patient groups. However, aortic valve reoperation rates at 10 years follow-up were higher in bicuspid aortic valve group patients compared to tricuspid aortic valve group patients.

Background Aortic valve sparing surgery (AVS), in combination with aortic cusp repair (ACR), still raises many questions about the increased surgical complexity and applicability for patients with pure aortic valve regurgitation (AR). The aim of this study was to investigate our long-term outcomes and predictors of recurrent AR (> 2+) after AVS and reconstructive cusp surgery. Methods We reviewed data of 81 patients who underwent AVS (a reimplantation technique) with concomitant ACR for AR and or dilatation of the aortic root at our institution during the period from April 2004 to October 2016. On preoperative echocardiography, the majority of the patients, 70 (86.4%) presented with severe AR grade (> 3+) and 28 (34.5%) of the patients had the bicuspid phenotype. Time to event analysis (long-term survival, freedom from reoperation, and recurrence of AR > 2+) was performed with the Kaplan–Meier method. Multivariate Cox regression risk analysis was performed to identify independent predictors of recurrent AR (> 2+). The mean follow-up was 5.3 ± 3.3 years and 100% complete. Results The in-hospital (30-day) mortality rate after elective surgery was 1.2%. The overall actuarial survival rates were 92.9 ± 3.1% and 90.4 ± 3.9% at five and 10 years, respectively. Actuarial freedom from recurrent AR (> 2+) was 83.7 ± 4.5% within the cohort at five and 10 years. The cumulative freedom from all causes of cardiac reoperation was 94.2 ± 2.8% within the cohort at 10 years. Neither bleeding nor thromboembolic or permanent neurologic events were reported during follow-up. By multivariate analysis, independent predictors of reccurent AR (> 2+) were an effective height lower than 9 mm (p= 0.02) and intraoperative residual mild AR (p= 0.0001). Conclusions AVS with ACR, combined in a systematic fashion, is a safe and reproducible option with low risk of long-term valve related events and normal life expectancy for patients with pure aortic regurgitation. The competent aortic valve and effective height, not lower than 9 mm intraoperatively, are mandatory to achieve long-lasting AV competency.

Objective:Surgical management of infective endocarditis continues to be challenging and is associated with significant morbidity and mortality. The objective of our study was to determine the risk factors and conditions associated with poor early infective endocarditis surgical treatment outcomes—30-day postoperative mortality.Methods:A total of 124 patients who underwent surgery for infective endocarditis at the Hospital of Lithuanian University of Health Sciences Kaunas Clinics from January 2010 to December 2017 were retrospectively included in this study. The primary endpoints were 30-day postoperative mortality and identification of risk factors associated with it. Secondary endpoints were early postoperative outcomes and complication rates.Results:During the study period, 124 patients with infective endocarditis underwent cardiac surgery, presenting an overall 30-day postoperative mortality rate of 10.48%. Mean age was 58 ± 14.4 years with 95 (76.61%) males. Independent predictive factors of early mortality were age >63 years (odds ratio = 6.4, 95% confidence interval = 1.66-24.66, p = 0.003), body mass index >30 kg/m² (odds ratio = 7.74, 95% confidence interval = 2.20-27.27, p = 0.003), and ischemic heart disease (odds ratio, 6.6, 95% confidence interval = 1.62-26.90, p = 0.003), as well as intraoperative parameters—prolonged aortic cross-clamp >84.5 minutes (odds ratio = 3.79, 95% confidence interval = 1.10-13.08, p = 0.03) and cardiopulmonary bypass time >107.5 minutes (odds ratio = 10.0, 95% confidence interval = 1.26-79.58, p = 0.023). Staphylococcus aureus infection (odds ratio = 5.04, 95% confidence interval = 1.29-19.64, p = 0.012), infective endocarditis–related intracardiac complication such as paravalvular abscess detected by transesophageal echocardiography (odds ratio = 4.32, 95% confidence interval = 1.31-14.25, p = 0.01), and infective endocarditis complicated by septic or cardiogenic shock (odds ratio, 18.43, 95% confidence interval = 4.59-73.98, p = 0.001) were statistically significant factors for increased risk of 30-day postoperative mortality.Conclusion:Surgical treatment of infective endocarditis showed good results in our center. The independent predictors of 30-day postoperative mortality for patients who underwent cardiac surgery for infective endocarditis were age, body mass index, ischemic heart disease, prolonged aortic cross-clamp and cardiopulmonary bypass time, Staphylococcus aureus infection, paravalvular abscess, and septic or cardiogenic shock.

The emergence of optical imaging has revolutionized the investigation of cardiac electrical activity and associated disorders in various cardiac pathologies. The electrical signals of the heart and the propagation pathways are crucial for elucidating the mechanisms of various cardiac pathological conditions, including arrhythmia. The synthesis of near-infrared voltage-sensitive dyes and the voltage sensitivity of the FDA-approved dye Cardiogreen have increased the importance of optical mapping (OM) as a prospective tool in clinical practice. We aimed to develop a method for the high-spatiotemporal-resolution OM of the large animal hearts in situ using di-4-ANBDQBS and Cardiogreen under patho/physiological conditions. OM was adapted to monitor cardiac electrical behaviour in an open-chest pig heart model with physiological or artificial blood circulation. We detail the methods and display the OM data obtained using di-4-ANBDQBS and Cardiogreen. Activation time, action potential duration, repolarization time and conduction velocity maps were constructed. The technique was applied to track cardiac electrical activity during regional ischaemia and arrhythmia. Our study is the first to apply high-spatiotemporal-resolution OM in the pig heart in situ to record cardiac electrical activity qualitatively under artificial blood perfusion. The use of an FDA-approved voltage-sensitive dye and artificial blood perfusion in a swine model, which is generally accepted as a valuable pre-clinical model, demonstrates the promise of OM for clinical application.

Objectives: To evaluate the impact of concomitant tricuspid valve (TV) repair on the right ventricular (RV) function postoperatively and within the 6 months following degenerative mitral valve (MV) repair. Methods: The prospective study included 37 patients (mean age 57.32 ± 2.13 years) with severe MV regurgitation due to primary MV prolapse. Nineteen underwent successful MV repair (TV(−) group). Additional TV repair due to moderate-to-severe TV regurgitation was performed in 18 (TV(+) group). Two-dimensional (2D) speckle-tracking and tissue Doppler echocardiography was performed for all patients before surgery and 7 days and 6 months after surgery. Results: Preoperative dimensions and indices of RV longitudinal function did not differ between the groups (right ventricle end-diastolic diameter (RVEDD) was 33.53 ± 0.94 mm vs. 34.67 ± 1.72 mm, tricuspid annular systolic motion (S’) was 15.06 ± 0.85 cm/s vs. 16.0 ± 1.27 cm/s, tricuspid annular plane systolic excursion (TAPSE) was 24.02 ± 1.06 mm vs. 22.4 ± 1.36 mm, respectively; p>0.05). RVEDD decreased significantly and did not change within the follow-up in the TV(−) group. In the TV(+) group, RVEDD decreased early after surgery and more markedly six months later in comparison to the TV(−) group. Indices of RV systolic longitudinal function decreased early after surgery and had a tendency to increase after six months in both groups. Regional longitudinal strains of the lateral RV wall decreased early after surgery and improved within the six months in the TV(−) group and did not change significantly in the TV(+) group. Conclusions: Additional TV repair in degenerative MV repair more markedly reduces RV dimensions and does not have a negative impact on RV systolic function in comparison to an isolated MV repair although these conclusions are of limited value due to the lack of a control group.

The aim of the study was to evaluate early postoperative results of different surgical techniques of aortic root surgery. Material and methods. Between January 2004 and November 2007, a cohort of 83 patients underwent aortic root surgery in the Heart Center, Hospital of Kaunas University of Medicine. Patients were divided into three groups: Group 1 (18 patients) – reimplantation of the aortic valve within a vascular graft (David operation), Group 2 (48 patients) – replacement of the ascending aorta and aortic valve using a valved conduit (Bentall de Bono operation), and Group 3 (17 patients) – biological aortic root replacement. Study protocol included clinical data, operative data, and postoperative major adverse effects: reoperations for bleeding, stroke and lethal outcomes. Results. Patients undergoing biological aortic root replacement were older as compared with other groups. The mean age in the Group 1 was 50.3±3.5 years vs. 57±2.0 years in the Group 2 and 67.8±3.3 years in the Group 3 (P&lt, 0.05). The main indication for the aortic root surgery was the aneurysm of the aortic root and ascending aorta in the Group 1 and 2 patients (64.7% and 72%), while in the Group 3, the main indication was fibrocalcinosis of aortic valve, aortic annulus, and ascending aorta (61.1%). The 30-day hospital mortality rates were as follows: 5.8% (n=1), in the Group 1, 10.4% (n=5), in the Group 2, 5.5% (n=1), in the Group 3. In the early postoperative period, 11 reoperations were performed due to bleeding events: in the Group 1, after planned/emergency surgery (n=2/2), and in the Group 2 (n=1/6), respectively. The function of aortic valve improved significantly in all groups of patients early after surgery. In the Group 1, the degree of aortic regurgitation decreased from 2.5±0.8 to 1.1±0.6 (P&lt, 0.05), in the Groups 2 and 3, the mean gradient through the aortic valve decreased from 39.9±7.5 to 17.1±5.3 mm Hg and from 48.8±18.0 to 20.1±11.0 mm Hg, respectively (P&lt, 0.05). No reoperation for aortic valve failure before the discharge was required in all groups of patients, and neither thromboembolic complications nor stroke events were noted in any group. Conclusions. Different aortic root surgery techniques showed similar postoperative results. New aortic root surgery methods such as aortic root-preserving/sparing procedures and concurrent aortic valve leaflet repair or aortic root replacement with the bioprosthesis can be selected for a diverse class of aortic root pathology with low perioperative mortality rates and good early postoperative results.