RNA Sequencing Reveals Novel Transcripts from Sympathetic Stellate Ganglia During Cardiac Sympathetic Hyperactivity.

Cardiovascular disease is the most prevalent age-related illness worldwide, causing approximately 15 million deaths every year. Hypertension is central in determining cardiovascular risk and is a strong predictive indicator of morbidity and mortality; however, there remains an unmet clinical need for disease-modifying and prophylactic interventions. Enhanced sympathetic activity is a well-established contributor to the pathophysiology of hypertension, however the cellular and molecular changes that increase sympathetic neurotransmission are not known. The aim of this study was to identify key changes in the transcriptome in normotensive and spontaneously hypertensive rats. We validated 15 of our top-scoring genes using qRT-PCR, and network and enrichment analyses suggest that glutamatergic signalling plays a key role in modulating Ca2+ balance within these ganglia. Additionally, phosphodiesterase activity was found to be altered in stellates obtained from the hypertensive rat, suggesting that impaired cyclic nucleotide signalling may contribute to disturbed Ca2+ homeostasis and sympathetic hyperactivity in hypertension. We have also confirmed the presence of these transcripts in human donor stellate samples, suggesting that key genes coupled to neurotransmission are conserved. The data described here may provide novel targets for future interventions aimed at treating sympathetic hyperactivity associated with cardiovascular disease and other dysautonomias

Increased baseline ECG R-R dispersion predicts improvement in systolic function after atrial fibrillation ablation.

BackgroundAtrial fibrillation (AF) is associated with left ventricular (LV) systolic dysfunction which may improve after AF ablation. We hypothesised that increased ventricular irregularity, as measured by R-R dispersion on the baseline ECG, would predict improvement in the left ventricular ejection fraction (LVEF) after AF ablation.MethodsPatients with LVEF <50% at two US centres (2007-2016), having both a preablation and postablation echocardiogram or cardiac MRI, were included. LVEF improvement was defined as absolute increase in LVEF by >7.5%. Multivariable logistic regression (restricted to echocardiographic/ECG variables) was performed to evaluate predictors of LVEF improvement.ResultsFifty-two patients were included in this study. LVEF improved in 30 patients (58%) and was unchanged/worsened in 22 patients (42%). Those with versus without LVEF improvement had an increased baseline R-R dispersion (645±155 ms vs 537±154 ms, p=0.02, respectively). The average baseline heart rate in all patients was 93 beats per minute. After multivariable logistic regression, increased R-R dispersion (OR 1.59, 95% CI 1.00 to 2.55, p=0.03) predicted LVEF improvement.ConclusionsIncreased R-R dispersion on ECG was independently associated with improved systolic function after AF ablation. This broadens the existing knowledge of arrhythmia-induced cardiomyopathy, demonstrating that irregular electrical activation (as measured by increased R-R dispersion on ECG) is associated with a cardiomyopathy capable of improving after AF ablation

Ablating atrial fibrillation: A translational science perspective for clinicians

Although considerable progress has been made in developing ablation approaches to cure AF, outcomes are still suboptimal especially for persistent and long-lasting persistent AF. In this topical review, we review the arrhythmia mechanisms, both reentrant and non-reentrant, that are potentially relevant to human AF at various stages/settings. We describe arrhythmia mapping techniques used to distinguish between the different mechanisms, with a particular focus on the detection of rotors. We discuss which arrhythmia mechanisms are likely to respond to ablation, and the challenges and prospects for improving upon current ablation strategies to achieve better outcomes

Crystal and molecular structure of (9R)-10,11-dihydro-6′-methoxy-cinchonan-9-ol-4-chlorobenzoate hydrochloride

The crystal structure of the title compound has been determined by single crystal X-ray diffraction methods. C 27H 29N 2O 3Cl.HCl is one of the cinchona alkaloids. It crystallizes in the space group P2 12 12 1 with a = 11.745(3), b = 12.353(6), c = 17.253(6) Å and Z = 4. The structure was refined to a final R value of 0.062 for 2155 observed reflections. The C-N distances are unequal in the quinoline ring system. In quinulidine ring, the bonds around N are more tetrahedral. The spatial arrangement and torsion angles show the open conformation of the molecule. The molecular packing is stabilized by hydrogen bonding

Novel reductive coupling of aldimines by indium under aqueous conditions

Aldimines are reductively coupled by indium to vicinal diamines in aqueous ethanol in good yields

Crystal and molecular structure of trans-(±)-3-acetoxy-2- (4methoxyphenyl)-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-1-oxide

The title compound is a structurally related isomer of diltiazem, a well known drug. This compound (C18H17NO5S) crystallizes in the space group P21/n with a = 13.803(4), b = 7.704(3), c = 16.093(3) à , β= 105.37(2)°, Z = 4, V = 1650.1(9) à ,3. The least-squares refinement gave residual index R = 0.067 for 2831 observed reflections. The distorted seven-membered ring in the molecule shows twist-boat conformation. Hydrogen bonds in which the amide group at one molecule and a carbonyl group in the adjacent molecule are involved to form centrosymmetric dimers in the crystal. © 2006 WILEY-VCH Verlag GmbH & Co. KGaA

(+)-cis-3-hydroxy-2-(4-methoxyphenyl)-4-oxo-2,3,4,5-tetrahydro-1,5-benzo thiazepine 1-oxide

The title compound, C16H15NO4S, is a diltiazem drug intermediate. Diltiazem is an enantiomerically pure drug with calcium antagonist activity. The molecular packing is stabilized by hydrogen bonding. The amide and hydroxide groups form hydrogen bonds with neighbouring molecules. The seven-membered ring is in a twist-boat conformation. The methoxyphenyl group deviates slightly from planarity but the benzene ring is planar

Ablating atrial fibrillation: A translational science perspective for clinicians.

Although considerable progress has been made in developing ablation approaches to cure atrial fibrillation (AF), outcomes are still suboptimal, especially for persistent and long-lasting persistent AF. In this topical review, we review the arrhythmia mechanisms, both reentrant and nonreentrant, that are potentially relevant to human AF at various stages/settings. We describe arrhythmia mapping techniques used to distinguish between the different mechanisms, with a particular focus on the detection of rotors. We discuss which arrhythmia mechanisms are likely to respond to ablation, and the challenges and prospects for improving upon current ablation strategies to achieve better outcomes