So far, the optical mapping of cardiac electrical signals using voltage-sensitive fluorescent dyes has only been performed in experimental studies because these dyes are not yet approved for clinical use. It was recently reported that the well-known and widely used fluorescent dye indocyanine green (ICG), which has FDA approval, exhibits voltage sensitivity in various tissues, thus raising hopes that electrical activity could be optically mapped in the clinic. The aim of this study was to explore the possibility of using ICG to monitor cardiac electrical activity. Optical mapping experiments were performed on Langendorff rabbit hearts stained with ICG and perfused with electromechanical uncouplers. The residual contraction force and electrical action potentials were recorded simultaneously. Our research confirms that ICG is a voltage-sensitive dye with a dual-component (fast and slow) response to membrane potential changes. The fast component of the optical signal (OS) can have opposite polarities in different parts of the fluorescence spectrum. In contrast, the polarity of the slow component remains the same throughout the entire spectrum. Separating the OS into these components revealed two different voltage-sensitivity mechanisms for ICG. The fast component of the OS appears to be electrochromic in nature, whereas the slow component may arise from the redistribution of the dye molecules within or around the membrane. Both components quite accurately track the time of electrical signal propagation, but only the fast component is suitable for estimating the shape and duration of action potentials. Because ICG has voltage-sensitive properties in the entire heart, we suggest that it can be used to monitor cardiac electrical behavior in the clinic.
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.
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.
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.
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.
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