Selective Inhibition of Pulmonary Vein Excitability by Constitutively Active GIRK Channels Blockade in Rats.

Pulmonary veins (PV) are the main source of ectopy, triggering atrial fibrillation. This study investigated the roles of G protein-coupled inwardly rectifying potassium (GIRK) channels in the PV and the left atrium (LA) of the rat. Simultaneous intracellular microelectrode recording from the LA and the PV of the rat found that in the presence or absence of acetylcholine, the GIRK channel blocker tertiapin-Q induced AP duration elongation in the LA and the loss of over-shooting AP in the PV, suggesting the presence of constitutively active GIRK channels in these tissues.

Spiky: An ImageJ Plugin for Data Analysis of Functional Cardiac and Cardiomyocyte Studies.

Introduction And Objective: Nowadays, investigations of heart physiology and pathophysiology rely more and more upon image analysis, whether for the detection and characterization of events in single cells or for the mapping of events and their characteristics across an entire tissue. These investigations require extensive skills in image analysis and/or expensive software, and their reproducibility may be a concern. Our objective was to build a robust, reliable and open-source software tool to quantify excitation-contraction related experimental data at multiple scales, from single isolated cells to the whole heart.

Gabapentinoid-induced peripheral edema and acute heart failure: A translational study combining pharmacovigilance data and in vitro animal experiments.

Introduction: Gabapentinoids are ligands of the α2-δ subunit of voltage-gated calcium channels (Cav) that have been associated with a risk of peripheral edema and acute heart failure in connection with a potentially dual mechanism, vascular and cardiac.

Objectives & Methods: All cases of peripheral edema or heart failure involving gabapentin or pregabalin reported to the French Pharmacovigilance Centers between January 1, 1994 and April 30, 2020 were included to describe their onset patterns (e.g.

Automatic Activity Arising in Cardiac Muscle Sleeves of the Pulmonary Vein.

Ectopic activity in the pulmonary vein cardiac muscle sleeves can both induce and maintain human atrial fibrillation. A central issue in any study of the pulmonary veins is their difference from the left atrial cardiac muscle. Here, we attempt to summarize the physiological phenomena underlying the occurrence of ectopic electrical activity in animal pulmonary veins.

Thio-ether functionalized glycolipid amphiphilic compounds reveal a potent activator of SK3 channel with vasorelaxation effect.

The modulation of SK3 ion channels can be efficiently and selectively achieved by using the amphiphilic compound Ohmline (a glyco-glycero-ether-lipid). We report herein a series of Ohmline analogues featuring the replacement of one ether function by a thioether function located at the same position or shifted close to its initial position. The variation of the lipid chain length and the preparation of two analogues featuring either one sulfoxide or one sulfone moiety complete this series.

Aqueous Fraction from Relaxes Mesenteric Arteries of Normotensive and Hypertensive Rats through Calcium Current Reduction and Possibly Potassium Channels Modulation.

Background/objectives: L. ( (HS)) extract has a vascular relaxant effect on isolated rat thoracic aorta, but data on small resistance arteries, which play an important role on the development of hypertension, are still missing. The purposes of this study were (1) to assess the effect on isolated mesenteric arteries (MA) from normotensive (Wistar and Wistar-Kyoto (WKY)) and spontaneous hypertensive rats (SHR); (2) to elucidate the mechanism(s) of action underling the relaxant effect in light of bioactive components.

Selective inhibition of electrical conduction within the pulmonary veins by α1-adrenergic receptors activation in the Rat.

Pulmonary veins (PV) are involved in the pathophysiology of paroxysmal atrial fibrillation. In the rat, left atrium (LA) and PV cardiomyocytes have different reactions to α1-adrenergic receptor activation. In freely beating atria-PV preparations, we found that electrical field potential (EFP) originated from the sino-atrial node propagated through the LA and the PV.

A Novel Calcium-Mediated EMT Pathway Controlled by Lipids: An Opportunity for Prostate Cancer Adjuvant Therapy.

The composition of periprostatic adipose tissue (PPAT) has been shown to play a role in prostate cancer (PCa) progression. We recently reported an inverse association between PCa aggressiveness and elevated PPAT linoleic acid (LA) and eicosapentaenoic acid (EPA) content. In the present study, we identified a new signaling pathway with a positive feedback loop between the epithelial-to-mesenchymal transition (EMT) transcription factor Zeb1 and the Ca-activated K channel SK3, which leads to an amplification of Ca entry and cellular migration.

Functional Organotypic Cultures of Prostate Tissues: A Relevant Preclinical Model that Preserves Hypoxia Sensitivity and Calcium Signaling.

In prostate cancer research, there is a lack of valuable preclinical models. Tumor cell heterogeneity and sensitivity to microenvironment signals, such as hypoxia or extracellular calcium concentration, are difficult to reproduce. Here, we developed and characterized an ex vivo tissue culture model preserving these properties.

SarConfoCal: simultaneous sarcomere length and cytoplasmic calcium measurements for laser scanning confocal microscopy images.

Summary: Simultaneous recordings of myocytes contractility and their cytoplasmic calcium concentration allow powerful studies, particularly on heart failure and other cardiac dysfunctions. Such studies require dedicated and expensive experimental devices that are difficult to use. Thus we propose SarConfoCal, the first and only software to simultaneously analyse both cytoplasmic calcium variations (from fluorescence signal) and myocytes contractility (from sarcomere length measurement) on laser scanning confocal microscopy images.

SarcOptiM for ImageJ: high-frequency online sarcomere length computing on stimulated cardiomyocytes.

Accurate measurement of cardiomyocyte contraction is a critical issue for scientists working on cardiac physiology and physiopathology of diseases implying contraction impairment. Cardiomyocytes contraction can be quantified by measuring sarcomere length, but few tools are available for this, and none is freely distributed. We developed a plug-in (SarcOptiM) for the ImageJ/Fiji image analysis platform developed by the National Institutes of Health.

Automatic quantitative analysis of t-tubule organization in cardiac myocytes using ImageJ.

The transverse tubule system in mammalian striated muscle is highly organized and contributes to optimal and homogeneous contraction. Diverse pathologies such as heart failure and atrial fibrillation include disorganization of t-tubules and contractile dysfunction. Few tools are available for the quantification of the organization of the t-tubule system.

A TTX-sensitive resting Na+ permeability contributes to the catecholaminergic automatic activity in rat pulmonary vein.

Introduction: Ectopic activity arising from pulmonary veins (PV) plays a prominent role in the onset of atrial fibrillation in humans. Rat PV cardiac muscle cells have a lower resting membrane potential (RMP) than the left atria (LA) and presents in the presence of norepinephrine an automatic activity, which occurs in bursts. This study investigated the role of Na channels upon the RMP and the catecholaminergic automatic activity (CAA) in PV cardiac muscle.

Atrial and vascular oxidative stress in patients with heart failure.

Heart failure is characterized by a great number of metabolic and histological defects, however, previous studies did not provide strong evidence of a correlation between the antioxidant status of myocardial tissue itself and cardiac function. The goal of our study was to assess, in patients with heart failure consecutive to dilated cardiomyopathy (DCM), alterations in norepinephrine (NE), lipid peroxidation (malonedialdehyde: MDA) and iron levels in different parts of the myocardium and aorta, in relation to functional parameters. Biopsied heart samples were obtained from 12 DCM patients and from 4 brain-dead organ donors (Controls).

Effects of cadmium on cardiac metallothionein induction and ischemia-reperfusion injury in rats.

Myocardial ischemia-reperfusion injury is associated with an imbalance between the formation and the scavenging of reactive oxygen species. In this context, the protective role of the antioxidant metallothionein, a thiol-rich protein that is induced in different organs in response to heavy metals and oxidative conditions, has mainly been investigated in metallothionein-knockout mice or metallothionein-overexpressing mice. The aim of this study was to evaluate whether the administration of cadmium has a protective effect against cardiac ischemia-reperfusion injury and whether this is associated with induction of in vivo cardiac metallothionein.

Catecholaminergic automatic activity in the rat pulmonary vein: electrophysiological differences between cardiac muscle in the left atrium and pulmonary vein.

Ectopic activity in cardiac muscle within pulmonary veins (PVs) is associated with the onset and the maintenance of atrial fibrillation in humans. The mechanism underlying this ectopic activity is unknown. Here we investigate automatic activity generated by catecholaminergic stimulation in the rat PV.

An increased regional blood flow precedes mesenteric inflammation in rats treated by a phosphodiesterase 4 inhibitor.

The study was undertaken to assess the hemodynamic effects induced by a single dose of the phosphodiesterase 4 (PDE4) inhibitor, CI-1044, which is known to cause mesenteric vascular alterations in rats. In the present study, an administration of 160 mg/kg of CI-1044 caused perivascular and interstitial inflammation, with infiltrates of admixed neutrophils and macrophages but without evidence of vascular necrosis (ileum, 15/20 rats; duodenum + jejunum, 7/20 rats). Four hours after administration, blood pressure was decreased (- 13%).

Regional heterogeneity of decreased myocardial norepinephrine and increased lipid peroxidation levels in patients with end-stage failing heart secondary to dilated or ischemic cardiomyopathy.

Background: Regional alterations in norepinephrine (NE) and lipid peroxidation in the myocardium of patients with heart failure is not well known. This study was designed to investigate regional myocardial NE levels and lipid peroxidation index and their relationships with the functional parameters in two pathologic conditions: dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM).

Methods: Biopsied heart samples were obtained from 13 DCM and 10 ICM patients (orthotopic cardiac transplantation).

Contractile and relaxant properties of rat-isolated pulmonary veins related to localization and histology.

The aim of this study was to investigate the in vitro vasomotor properties of rat extra-and intralobar pulmonary veins (PVs) related to their localization and to assess the modulatory role of endothelium on these properties. Segments from PVs were mounted in small vessel myograph and stretched at various diameters (D(10), D(20), D(30)) corresponding to intraluminal pressures of 10, 20 or 30 mmHg. At D(10) or D(20), contractile responses to phenylephrine, U46619 and angiotensin II of distal intralobar part of PVs were smaller compared with those of proximal extralobar part, but no longer different when distal part was stretched at D(30).

Metallothionein induction in the liver, kidney, heart and aorta of cadmium and isoproterenol treated rats.

Metallothionein (MT), induced in different organs in response to heavy metals and oxidative conditions, exerts antioxidant properties and thus could be implicated in cardiovascular physiopathology. The aim of this study was to investigate the capacity of cadmium (Cd) and isoproterenol to induce in vivo MT not only in rat liver and kidneys but also in heart and aorta. Tissue MT levels, catalase (CAT) and glutathione peroxidase (GPX) activities were assayed at different times after Cd or isoproterenol injection.

Effect of a methionine-supplemented diet on the blood pressure of Sprague-Dawley and deoxycorticosterone acetate-salt hypertensive rats.

The objectives of the present study were to evaluate the effects of a methionine-supplemented diet on systolic blood pressure (BP) and vasomotor functions in Sprague-Dawley (SD) and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. SD and DOCA rats were fed a normal or a methionine (8 g/kg)-supplemented diet for 10 weeks. Systolic BP was monitored and plasma homocysteine, methionine and cysteine levels were determined at the end of the experiment.

Direct demonstration of nitric oxide formation in organs of rabbits treated by transdermal glyceryl trinitrate using an in vivo spin trapping technique.

Glyceryl trinitrate (GTN) is commonly delivered by a patch for the treatment of angina pectoris. The idea is now generally accepted that GTN requires a biotransformation process that activates the drug, in particular through nitric oxide (NO) generation. However, the pharmacokinetics of NO delivery from GTN still remains obscure.

Identification and quantification of free radicals during myocardial ischemia and reperfusion using electron paramagnetic resonance spectroscopy.

There is general agreement that free radicals are involved in reperfusion injury. Electron paramagnetic resonance (EPR) spectroscopy can be considered as the more suitable technique to directly measure and characterize free radical generation during myocardial ischemia and reperfusion. There are essentially two approaches used in the detection of unstable reactive species: freezing technique and spin traps.

Evidence for the extrapulmonary localization of inhaled nitric oxide.

Inhaled nitric oxide (NO) has emerged as a promising pulmonary vasodilator to treat pulmonary hypertension associated with heart disease and ventilation/perfusion mismatching. However, the pharmacokinetics of inhaled NO still remains obscure and its cardiopulmonary selectivity appears to be increasingly under debate. In the present study measured NO content and levels of cyclic guanosine 3',5'monophosphate (cGMP), a mediator of NO-induced vasodilation, in a variety of organs from rats subjected to NO inhalation.

Effect of a methionine-supplemented diet on the blood pressure of Wistar-Kyoto and spontaneously hypertensive rats.

The objectives of the present work were to evaluate the effect of a methionine-supplemented diet as a model of hyperhomocysteinaemia on the systolic blood pressure (BP) and vasomotor functions of aortic rings in Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). WKY and SHR rats, randomised into four groups, were fed a normal semisynthetic diet or a methionine (8 g/kg)-supplemented diet for 10 weeks. Systolic BP was measured non-invasively.