Dysregulation of epicardial adipose tissue in cachexia due to heart failure. the role of natriuretic peptides and cardiolipin

Background: Cachexia worsens long-term prognosis of patients with heart failure (HF). Effective treatment of cachexia is missing. We seek to characterize mechanisms of cachexia in adipose tissue, which could serve as novel targets for the treatment. Methods: The study was conducted in advanced HF patients (n = 52; 83% male patients) undergoing heart transplantation. Patients with ≥7.5% non-intentional body weight (BW) loss during the last 6 months were rated cachectic. Clinical characteristics and circulating markers were compared between cachectic (n = 17) and the remaining, BW-stable patients. In epicardial adipose tissue (EAT), expression of selected genes was evaluated, and a combined metabolomic/lipidomic analysis was performed to assess (i) the role of adipose tissue metabolism in the development of cachexia and (ii) potential impact of cachexia-associated changes on EAT-myocardium environment. Results: Cachectic vs. BW-stable patients had higher plasma levels of natriuretic peptide B (BNP; 2007 ± 1229 vs. 1411 ± 1272 pg/mL; P = 0.010) and lower EAT thickness (2.1 ± 0.8 vs. 2.9 ± 1.4 mm; P = 0.010), and they were treated with ~2.5-fold lower dose of both β-blockers and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACE/ARB-inhibitors). The overall pattern of EAT gene expression suggested simultaneous activation of lipolysis and lipogenesis in cachexia. Lower ratio between expression levels of natriuretic peptide receptors C and A was observed in cachectic vs. BW-stable patients (0.47 vs. 1.30), supporting activation of EAT lipolysis by natriuretic peptides. Fundamental differences in metabolome/lipidome between BW-stable and cachectic patients were found. Mitochondrial phospholipid cardiolipin (CL), specifically the least abundant CL 70:6 species (containing C16:1, C18:1, and C18:2 acyls), was the most discriminating analyte (partial least squares discriminant analysis; variable importance in projection score = 4). Its EAT levels were higher in cachectic as compared with BW-stable patients and correlated with the degree of BW loss during the last 6 months (r = −0.94; P = 0.036). Conclusions: Our results suggest that (i) BNP signalling contributes to changes in EAT metabolism in cardiac cachexia and (ii) maintenance of stable BW and ‘healthy’ EAT-myocardium microenvironment depends on the ability to tolerate higher doses of both ACE/ARB inhibitors and β-adrenergic blockers. In line with preclinical studies, we show for the first time in humans the association of cachexia with increased adipose tissue levels of CL. Specifically, CL 70:6 could precipitate wasting of adipose tissue, and thus, it could represent a therapeutic target to ameliorate cachexia

Detailed Anatomical and Electrophysiological Models of Human Atria and Torso for the Simulation of Atrial Activation

Atrial arrhythmias, and specifically atrial fibrillation (AF), induce rapid and irregular activation patterns that appear on the torso surface as abnormal P-waves in electrocardiograms and body surface potential maps (BSPM). In recent years both P-waves and the BSPM have been used to identify the mechanisms underlying AF, such as localizing ectopic foci or high-frequency rotors. However, the relationship between the activation of the different areas of the atria and the characteristics of the BSPM and P-wave signals are still far from being completely understood. In this work we developed a multi-scale framework, which combines a highly-detailed 3D atrial model and a torso model to study the relationship between atrial activation and surface signals in sinus rhythm. Using this multi scale model, it was revealed that the best places for recording P-waves are the frontal upper right and the frontal and rear left quadrants of the torso. Our results also suggest that only nine regions (of the twenty-one structures in which the atrial surface was divided) make a significant contribution to the BSPM and determine the main P-wave characteristics.This work was partially supported by the "VI Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica" from the Ministerio de Economia y Competitividad of Spain and the European Commission (European Regional Development Funds - ERDF - FEDER), Award Number: TIN2012-37546-C03-01 (Recipient: Ana Ferrer); the "Programa Estatal de Investigacion, Desarrollo e Innovacion Orientado a los Retos de la Sociedad" from the Ministerio de Economia y Competitividad and the European Commission (European Regional Development Funds - ERDF - FEDER), Award Number: TIN2014-59932-JIN (Recipient: Rafael Sebastion); and the "Programa Prometeo" from the Generalitat Valenciana, Award Number: 2012/030 (Recipient: Laura Martinez).Ferrer Albero, A.; Sebastián Aguilar, R.; Sánchez Quintana, D.; Rodriguez, JF.; Godoy, EJ.; Martinez, L.; Saiz Rodríguez, FJ. (2015). Detailed Anatomical and Electrophysiological Models of Human Atria and Torso for the Simulation of Atrial Activation. PLoS ONE. 10(11):1-29. https://doi.org/10.1371/journal.pone.0141573S129101

Atrial Septal Aneurysm in Adult Patients of Therapeutic Hospital

Aim. To study detection of atrial septal aneurysm (ASA) by transthoracic echocardiography in patients of the older age group of the therapeutic hospital, as well as combinations with other structural disorders of the heart and blood vessels, as well as other signs of congenital connective tissue dysplasia (CCTD) of other localization.Material and methods. Identification of ASA as well as other signs of CCTD was performed in patients ≥40 years hospitalized due to exacerbation of therapeutic diseases (n=1119), which had transthoracic echocardiography.Results. ASA was found in 1.34% of patients (n=15). Undifferentiated connective tissue dysplasia was diagnosed in 14 (93.3%) ASA patients. Prolapse of mitral (60%), tricuspid (33.3%) or both atrio-ventricular valves of the heart (6.7%), patent foramen ovale (33.3%), rudimentary Eustachian valve (6.7%), additional ventricle chords (13.3%), Valsalva sinus dilation (6.7%) was found in ASA patients. 14 (93.3%) patients had electrocardiography signs of cardiac rhythm and conduction disorders. Chronic venous insufficiency (100%), disorders of the musculoskeletal system (100%), hiatal hernia (40%), anterior abdominal wall hernia (46.7%), nephroptosis (46.7%), kidney cysts (33.3%) intestinal diverticula and dolichosigma (26.7%), bronchiectasis (6.7%) were also found.Conclusion. ASA was found in 1.34% of patients in a therapeutic hospital ≥40 years. Clinically significant and prognostically unfavorable CCTDs were not found in ASA patients in this study. However, physicians should consider the possibility of the presence of other abnormalities of the heart and large vessels, as well as other systems and organs that can lead to fatal events, in these patients

Presentation of Suitable Topologies to Create a Generic Ultrasonic Puls Generator for Nondestructive Flaw Detection

I detta examinationsarbetesrapport för högskoleingenjörsexamen inom Elektronik, presenteras en utredning för att svara på vad som skulle vara den mest generiska pulsgeneratorn för ultraljudstestning inom det klassiska intervallet 0.5 till 15 MHz. Det presenteras flera variabler i teorin, som påverkar en testsignal och varför det inte går att beräkna vad en generisk pulsgenerator bör åstadkomma. Denna rapport presenterar vilka pulsgeneratorer det finns och vad de mer högpresterande pulsgeneratorerna beskrivna i vetenskapliga forskningsresultat har presterat. Samt vilka tekniker som finns och varför vissa tekniker inte är lämpliga. Vid slutet av denna examinationsarbetesrapport presenteras, med hjälp av några antaganden om vad en generisk pulsgenerator behöver prestera, dras en slutsats om vilken av de föreslagna pulsgeneratorerna som är mest generisk.This bachelor thesis, is a trial in answering what would be a generic pulse generator for ultrasonic testing in the classic test range of 0.5 to 15 MHz. It also goes through multiple variables that affects a test signal and why it really isn't possible to precalculate what a generical pulse generators should achive, in the theory chapter. This thesis also goes through what different types of pulse generators there is and what some of the more high performance pulse generators proposed in scientific articles have achieved and what techniques that have been used and why some techniques are not suitable. In the end of this thesis there is a trial with some assumptions about what a generical pulse generator should achieve, to come to a conclusion about which pulse generator from the proposed ones would be the best generical pulse generator to go with