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https://www.readbyqxmd.com/read/28644868/electrophysiological-alterations-in-a-murine-model-of-chronic-coxsackievirus-b3-myocarditis
#1
Sven Kaese, Robert Larbig, Matthias Rohrbeck, Gerrit Frommeyer, Dirk Dechering, Jan Olligs, Sabine Schönhofer-Merl, Rainer Wessely, Karin Klingel, Guiscard Seebohm, Lars Eckardt
INTRODUCTION: Coxsackievirus B3 (CVB3) is known to induce acute and chronic myocarditis. Most infections are clinically unapparent but some patients suffer from ventricular arrhythmias (VA) and sudden cardiac death (SCD). Studies showed that acute CVB3 infection may cause impaired function of cardiac ion channels, creating a proarrhythmic substrate. However, it is unknown whether low level CVB3+ expression in myocytes may cause altered cardiac electrophysiology leading to VA. METHODS: Cellular electrophysiology was used to analyze cellular action potentials (APs) and occurrence of afterdepolarizations from isolated cardiomyocytes of wildtype (WT) and transgenic CVB3ΔVP0 (CVB3+) mice...
2017: PloS One
https://www.readbyqxmd.com/read/28641963/modulation-of-the-heart-s-electrical-properties-by-the-anticonvulsant-drug-retigabine
#2
Lena Rubi, Michael Kovar, Eva Zebedin-Brandl, Xaver Koenig, Manuel Dominguez-Rodriguez, Hannes Todt, Helmut Kubista, Stefan Boehm, Karlheinz Hilber
Retigabine, currently used as antiepileptic drug, has a wide range of potential medical uses. Administration of the drug in patients can lead to QT interval prolongation in the electrocardiogram and to cardiac arrhythmias in rare cases. This suggests that the drug may perturb the electrical properties of the heart, and the underlying mechanisms were investigated here. Effects of retigabine on currents through human cardiac ion channels, heterologously expressed in tsA-201 cells, were studied in whole-cell patch-clamp experiments...
June 19, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28641785/acute-detachment-of-hexokinase-ii-from-mitochondria-modestly-increases-oxygen-consumption-of-the-intact-mouse-heart
#3
Rianne Nederlof, Simone Denis, Benjamin Lauzier, Christine Des Rosiers, Markku Laakso, Jacob Hagen, Carmen Argmann, Ronald Wanders, Riekelt H Houtkooper, Markus W Hollmann, Sander M Houten, Coert J Zuurbier
OBJECTIVE: Cardiac hexokinase II (HKII) can translocate between cytosol and mitochondria and change its cellular expression with pathologies such as ischemia-reperfusion, diabetes and heart failure. The cardiac metabolic consequences of these changes are unknown. Here we measured energy substrate utilization in cytosol and mitochondria using stabile isotopes and oxygen consumption of the intact perfused heart for 1) an acute decrease in mitochondrial HKII (mtHKII), and 2) a chronic decrease in total cellular HKII...
July 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28632748/trimetazidine-therapy-for-diabetic-mouse-hearts-subjected-to-ex-vivo-acute-heart-failure
#4
Emilene Breedt, Lydia Lacerda, M Faadiel Essop
Acute heart failure (AHF) is the most common primary diagnosis for hospitalized heart diseases in Africa. As increased fatty acid β-oxidation (FAO) during heart failure triggers detrimental effects on the myocardium, we hypothesized that trimetazidine (TMZ) (partial FAO inhibitor) offers cardioprotection under normal and obese-related diabetic conditions. Hearts were isolated from 12-14-week-old obese male and female diabetic (db/db) mice versus lean non-diabetic littermates (db/+) controls. The Langendorff retrograde isolated heart perfusion system was employed to establish an ex vivo AHF model: a) Stabilization phase-Krebs Henseleit buffer (10 mM glucose) at 100 mmHg (25 min); b) Critical Acute Heart Failure (CAHF) phase-(1...
2017: PloS One
https://www.readbyqxmd.com/read/28627809/ivabradine-reduces-digitalis-induced-ventricular-arrhythmias
#5
Gerrit Frommeyer, Jan Weller, Christian Ellermann, Nils Bögeholz, Patrick Leitz, Dirk G Dechering, Simon Kochhäuser, Kristina Wasmer, Lars Eckardt
The I(f) channel inhibitor ivabradine is recommended for treatment of heart failure but also affects potassium currents and thereby prolongs ventricular repolarization. The aim of the present study was to examine the electrophysiological effects of ivabradine on digitalis-induced ventricular arrhythmias. Thirteen rabbit hearts were isolated and Langendorff-perfused. After obtaining baseline data, the digitalis glycoside ouabain was infused (0.2μM). Monophasic action potentials and ECG showed a significant abbreviation of QT interval (-34ms,p<0...
June 19, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28606656/divergent-antiarrhythmic-effects-of-resveratrol-and-piceatannol-in-a-whole-heart-model-of-long-qt-syndrome
#6
Christian Ellermann, Julian Wolfes, Simon Kochhäuser, Dirk G Dechering, Florian Reinke, Kristina Wasmer, Lars Eckardt, Gerrit Frommeyer
BACKGROUND: The polyphenol resveratrol and its metabolite piceatannol have beneficial health effects including antiarrhythmic properties in ischemia/reperfusion. The objective of this study was to determine potential antiarrhythmic effects in acquired long-QT-syndrome (LQTS). METHODS AND RESULTS: 26 rabbit hearts were isolated and Langendorff-perfused. The IKr-blocker sotalol (100μM) was infused to mimic LQTS-2. Hearts were assigned to two groups. Sotalol significantly prolonged action potential duration (APD90) and QT-interval in both groups (group 1:APD90: +18ms, p<0...
June 3, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28599085/exploring-the-putative-role-of-trpv1-dependent-cgrp-release-in-remote-hind-preconditioning-induced-cardioprotection
#7
Puneet Kaur Randhawa, Amteshwar Singh Jaggi
Remote ischemic preconditioning (RIPC) is a phenomenon whereby transient non-lethal ischemia and reperfusion episodes confer protection against prolonged ischemia-reperfusion-induced injury. However, the underlying intracellular signaling has not been extensively explored. The present study aims to inspect the putative involvement of TRPV1 -dependent CGRP release in mediating remote hind limb preconditioning-induced cardioprotection. In the present study, remote hind limb preconditioning stimulus was delivered (4 consecutive episodes of 5 minutes of ischemia-reperfusion) using a blood pressure cuff tied at the inguinal level of the rat...
June 9, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28579963/olesoxime-inhibits-cardioplegia-induced-ischemia-reperfusion-injury-a-study-in-langendorff-perfused-rabbit-hearts
#8
Aida Salameh, Maren Keller, Ingo Dähnert, Stefan Dhein
Objective: During cardioplegia, which is often used in cardiac surgery, the heart is subjected to global ischemia/reperfusion injury, which can result in a post-operative impairment of cardiac function. Mitochondria permeability transition pores (MPTP) play a key role in cardiomyocyte survival after ischemia/reperfusion injury. It was shown in clinical settings that blockers of MPTP like cyclosporine might have a positive influence on cardiac function after cardioplegic arrest. Olesoxime, which is a new drug with MPTP blocking activity, has been introduced as a neuroprotective therapeutic agent...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28575091/repeated-exposure-to-methamphetamine-induces-sex-dependent-hypersensitivity-to-ischemic-injury-in-the-adult-rat-heart
#9
Boyd R Rorabaugh, Sarah L Seeley, Thorne S Stoops, Manoranjan S D'Souza
BACKGROUND: We previously reported that adult female, but not male rats that were prenatally exposed to methamphetamine exhibit myocardial hypersensitivity to ischemic injury. However, it is unknown whether hypersensitivity to ischemic injury develops when rats are exposed to methamphetamine during adulthood. The goal of this study was to determine whether methamphetamine exposure during adulthood sensitizes the heart to ischemic injury. METHODS: Adult male and female rats received daily injections of methamphetamine (5 mg/kg) or saline for 10 days...
2017: PloS One
https://www.readbyqxmd.com/read/28566490/n-methyl-d-asparate-receptors-activation-down-regulated-transient-outward-potassium-and-l-type-calcium-current-in-rat-models-of-depression
#10
Xin Liu, Shaobo Shi, Hongjie Yang, Chuan Qu, Yuting Chen, Jinjun Liang, Bo Yang
Objective Major depression is an important clinical factor in ventricular arrhythmia. Patients diagnosed with major depression overexpress N-methyl-d-aspartate receptors (NMDARs). Previous studies found that chronic NMDAR activation increases susceptibility to ventricular arrhythmias. We aimed to explore the mechanisms by which NMDAR activation may increase susceptibility to ventricular arrhythmias. Methods Male rats were randomly assigned to either normal environments as control (CTL) group or 4weeks of chronic mild stress(CMS) to produce a major depression disorder (MDD) model group...
May 31, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28560127/naproxen-and-diclofenac-attenuate-atorvastatin-induced-preconditioning-of-the-myocardium
#11
Zoltan Varga, Martina Nemcekova, Slavka Carnicka, Veronika Slezakova, Miriam Petrova, Marek Majdan, Tana Ravingerova, Viera Kristova
Statins reduce infarct size (IS) in ischemia-reperfusion injury of the myocardium. Inhibition of cyclooxygenase-2 (COX-2) attenuates this benefit. We investigated the effect of two widely used non-selective non-steroidal anti-inflammatory drugs (NSAIDs) with different degree of anti-COX-2 activity on atorvastatin-mediated preconditioning. Wistar rats received oral atorvastatin (10 mg∙kg(-1)∙day(-1)), naproxen (10 mg∙kg(-1)∙day(-1)), diclofenac (8 mg∙kg(-1)∙day(-1)), atorvastatin+naproxen, atorvastatin+diclofenac or water for three days...
April 29, 2017: Curēus
https://www.readbyqxmd.com/read/28559847/high-sensitivity-of-sirt3-deficient-hearts-to-ischemia-reperfusion-is-associated-with-mitochondrial-abnormalities
#12
Rebecca M Parodi-Rullán, Xavier Chapa-Dubocq, Pedro J Rullán, Sehwan Jang, Sabzali Javadov
Aim: Sirtuins are NAD(+)-dependent deacetylases that regulate cell metabolism through protein acetylation/deacetylation, and SIRT3 is the major deacetylase among mitochondrial isoforms. Here, we elucidated the possible role of acetylation of cyclophilin D, a key regulator of the mitochondrial permeability transition pore (mPTP), in mitochondria-mediated cardiac dysfunction induced by ischemia-reperfusion (IR) in wild type (WT) and SIRT3 knockout (SIRT3(-/-)) mice. Materials and Methods: Isolated and Langendorff-mode perfused hearts of WT and SIRT3(-/-) mice were subjected to 25-min global ischemia followed by 60-min of reperfusion in the presence or absence of the mPTP inhibitor, sanglifehrin A (SfA)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28556923/antiarrhythmic-properties-of-ivabradine-in-an-experimental-model-of-short-qt-syndrome
#13
Gerrit Frommeyer, Jan Weller, Christian Ellermann, Sven Kaese, Simon Kochhäuser, Philipp S Lange, Dirk G Dechering, Lars Eckardt
The If channel inhibitor ivabradine is recommended for treatment of chronic heart failure. However, ivabradine also inhibits human ether-a-go-go (hERG) mediated potassium currents. The aim of the present study was to assess the electrophysiologic effects of ivabradine in an experimental model of short-QT-syndrome. 12 rabbit hearts were isolated and Langendorff-perfused. After obtaining baseline data, pinacidil, an IK-ATP channel opener, was infused (1μM). Eight endo- and epicardial monophasic action potentials and a 12-lead ECG showed a significant abbreviation of QT interval (-32ms,p<0...
May 29, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28554962/local-transmural-action-potential-gradients-are-absent-in-the-isolated-intact-dog-heart-but-present-in-the-corresponding-coronary-perfused-wedge
#14
Bastiaan J Boukens, Veronique M F Meijborg, Charly N Belterman, Tobias Opthof, Michiel J Janse, Richard B Schuessler, Ruben Coronel, Igor R Efimov
The left ventricular (LV) coronary-perfused canine wedge preparation is a model commonly used for studying cardiac repolarization. In wedge studies, transmembrane potentials typically are recorded; whereas, extracellular electrical recordings are commonly used in intact hearts. We compared electrically measured activation recovery interval (ARI) patterns in the intact heart with those recorded at the same location in the LV wedge preparation. We also compared electrically recorded and optically obtained ARIs in the LV wedge preparation...
May 2017: Physiological Reports
https://www.readbyqxmd.com/read/28552884/ranolazine-facilitates-termination-of-ventricular-tachyarrhythmia-associated-with-acute-myocardial-ischemia-through-suppression-of-late-ina-mediated-focal-activity
#15
Takashi Ogawa, Haruo Honjo, Masatoshi Yamazaki, Yasunori Kushiyama, Ichiro Sakuma, Itsuo Kodama, Kaichiro Kamiya
BACKGROUND: Ventricular tachycardia/fibrillation (VT/VF) associated with acute myocardial ischemia is the most common cause of sudden cardiac death, but its underlying mechanisms are incompletely understood. It is hypothesized that late Na(+)current (INa) contributes to arrhythmogenic activity in ischemic myocardium.Methods and Results:Langendorff-perfused rabbit hearts with regional ischemia in ventricles were optically mapped. Perfusion with ranolazine (10 μmol/L), a selective inhibitor of lateINa, significantly reduced excitation frequency and facilitated termination of VT/VF induced after occlusion of the left main coronary trunk...
May 26, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28544853/microrna-34a-protect-myocardial-cells-against-ischemia-reperfusion-injury-through-inhibiting-autophagy-via-regulating-tnf%C3%AE-expression
#16
Haifeng Shao, Lili Yang, Li Wang, Bozan Tang, Jian Wang, Qiang Li
BACKGROUND: Ischemia/reperfusion (I/R) accompanying with the blood supply restored after myocardial infarction. Myocardial I/R injury relieves when autophagy decreased. MicroRNA-34a(miR-34a) regulate autophagy in renal I/R injury model. But whether it can affect cardiac I/R injury remains studying. This study investigated how miR-34a in protecting myocardial cells against I/R injury through inhibit autophagy via regulating tumor necrosis factor α (TNFα) . METHODS: Constructed the I/R model in vivo with Langendorff; treated Neonatal Rat cardiomyocyte to make H/R injury model in vitro with hypoxia/reoxygenation (H/R) method...
May 25, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28542320/the-ik1-kir2-1-channel-agonist-zacopride-prevents-and-cures-acute-ischemic-arrhythmias-in-the-rat
#17
Xu-Wen Zhai, Li Zhang, Yun-Fei Guo, Ying Yang, Dong-Ming Wang, Yan Zhang, Pan Li, Yi-Fan Niu, Qi-Long Feng, Bo-Wei Wu, Ji-Min Cao, Qing-Hua Liu
Arrhythmogenesis in acute myocardial infarction (MI) is associated with depolarization of resting membraine potential (RMP) and decrease of inward rectifier potassium current (IK1) in cardiomyocytes. However, clinical anti-arrhythmic agents that primarily act on RMP by enhancing the IK1 channel are not currently available. We hypothesized that zacopride, a selective and moderate agonist of the IK1/Kir2.1 channels, prevents and cures acute ischemic arrhythmias. To test this viewpoint, adult Sprague-Dawley (SD) rats were subjected to MI by ligating the left main coronary artery...
2017: PloS One
https://www.readbyqxmd.com/read/28536897/validation-of-myocardial-perfusion-quantification-by-dynamic-ct-in-an-ex-vivo-porcine-heart-model
#18
Gert Jan Pelgrim, Marco Das, Sjoerd van Tuijl, Marly van Assen, Frits W Prinzen, Marco Stijnen, Matthijs Oudkerk, Joachim E Wildberger, Rozemarijn Vliegenthart
To test the accuracy of quantification of myocardial perfusion imaging (MPI) using computed tomography (CT) in ex-vivo porcine models. Five isolated porcine hearts were perfused according to Langendorff. Hearts were perfused using retrograde flow through the aorta and blood flow, blood pressure and heart rate were monitored throughout the experiment. An inflatable cuff was placed around the circumflex (Cx) artery to create stenosis grades which were monitored using a pressure wire, analysing perfusion at several fractional flow reserve values of 1...
May 23, 2017: International Journal of Cardiovascular Imaging
https://www.readbyqxmd.com/read/28507060/alogliptin-a-dipeptidyl-peptidase-4-inhibitor-alleviates-atrial-remodeling-and-improves-mitochondrial-function-and-biogenesis-in-diabetic-rabbits
#19
Xiaowei Zhang, Zhiwei Zhang, Yungang Zhao, Ning Jiang, Jiuchun Qiu, Yajuan Yang, Jian Li, Xue Liang, Xinghua Wang, Gary Tse, Guangping Li, Tong Liu
BACKGROUND: There is increasing evidence implicating atrial mitochondrial dysfunction in the pathogenesis of atrial fibrillation. In this study, we explored whether alogliptin, a dipeptidyl peptidase-4 inhibitor, can prevent mitochondrial dysfunction and atrial remodeling in a diabetic rabbit model. METHODS AND RESULTS: A total of 90 rabbits were randomized into 3 groups as follows: control group (n=30), alloxan-induced diabetes mellitus group (n=30), and alogliptin-treated (12...
May 15, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28502095/the-impact-of-age-and-frailty-on-ventricular-structure-and-function-in-c57bl-6j-mice
#20
H A Feridooni, A E Kane, O Ayaz, A Boroumandi, N Polidovitch, R G Tsushima, R A Rose, S E Howlett
KEY POINTS: Heart size increases with age (called hypertrophy), and its ability to contract declines. However, these reflect average changes that may not be present, or present to the same extent, in all older individuals. That aging happens at different rates is well accepted clinically. People who are aging rapidly are frail and frailty is measured with a 'frailty index'. We quantified frailty with a validated mouse frailty index tool and evaluated the impacts of age and frailty on cardiac hypertrophy and contractile dysfunction...
June 15, 2017: Journal of Physiology
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