Abstract：
:Lower heart rate is associated with better survival in patients with multiple organ dysfunction syndrome (MODS), a disease mostly caused by sepsis. The benefits of heart rate reduction by ivabradine during MODS are currently being investigated in the MODIfY clinical trial. Ivabradine is a selective inhibitor of the pacemaker current If and since If is impaired by lipopolysaccharide (LPS, endotoxin), a trigger of sepsis, we aimed to explore If blocking potency of ivabradine under elevated endotoxin levels in human atrial cardiomyocytes. Treatment of myocytes with S-LPS (containing the lipid A moiety, a core oligosaccharide and an O-polysaccharide chain) but not R595 (an O-chain lacking LPS-form) caused If inhibition under acute and chronic septic conditions. The specific interaction of S-LPS but not R595 to pacemaker channels HCN2 and HCN4 proves the necessity of O-chain for S-LPS-HCN interaction. The efficacy of ivabradine to block If was reduced under septic conditions, an observation that correlated with lower intracellular ivabradine concentrations in S-LPS- but not R595-treated cardiomyocytes. Computational analysis using a sinoatrial pacemaker cell model revealed that despite a reduction of If under septic conditions, ivabradine further decelerated pacemaking activity. This novel finding, i.e. If inhibition by ivabradine under elevated endotoxin levels in vitro, may provide a molecular understanding for the efficacy of this drug on heart rate reduction under septic conditions in vivo, e.g. the MODIfY clinical trial.
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Scheruebel S,Koyani CN,Hallström S,Lang P,Platzer D,Mächler H,Lohner K,Malle E,Zorn-Pauly K,Pelzmann Bdoi
10.1016/j.yjmcc.2014.02.010subject
Has Abstractpub_date
2014-07-01 00:00:00pages
64-73eissn
0022-2828issn
1095-8584pii
S0022-2828(14)00060-1journal_volume
72pub_type
杂志文章abstract：:Coronary blood flow decreases cyclically in a partially occluded coronary artery of anesthetized dogs. Spontaneous aggregation and deaggregation of platelet plugs in the constricted artery have been indicated to be responsible for this phenomenon. A current hypothesis is that platelet aggregation may be determined by ...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/s0022-2828(84)80040-1
更新日期：1984-12-01 00:00:00
abstract：:Ischemia-induced myocardial potassium loss and post-ischemic potassium reuptake was quantitated in 8 open chest pigs during control conditions and during hemodynamic alterations which have been shown to increase steady state sarcolemmal potassium fluxes. Myocardial K+ balance was continuously computed before, during a...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/0022-2828(89)90673-1
更新日期：1989-12-01 00:00:00
abstract：:The agent 2,3-butanedione monoxime (BDM) has been reported to reduce the sensitivity of myofilament force development to calcium ions, without affecting the calcium transient in myocardium. One would predict, therefore, that BDM should reduce the contractile state of the heart without reducing the amount of oxygen tha...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/0022-2828(92)91093-k
更新日期：1992-08-01 00:00:00
abstract：:The relationship between reperfusion-induced arrhythmias and the size of the occluded zone was examined. The isolated perfuse rat heart was used because its negligible collateral flow maximizes susceptibility to arrhythmias and reduces variability. Ischemia lasting 10 min was followed by 10 min of reperfusion. A const...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/0022-2828(89)90828-6
更新日期：1989-06-01 00:00:00
abstract：:Introduced several decades ago, the dogma persists that ventricular myocytes are terminally differentiated cells and cardiac repair by myocyte regeneration is completely inhibited shortly after birth. On the basis that cardiac myocytes are unable to divide in the adult heart, myocyte growth under physiologic and patho...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章,评审
doi：10.1006/jmcc.2001.1506
更新日期：2002-02-01 00:00:00
abstract：:Recently discovered endothelin is a powerful vasoconstrictor of vascular smooth muscle in vitro, which also profoundly affects the mechanical function of the heart. An increased level of plasma endothelin in patients with acute myocardial infarction suggests the enhanced release of endothelin from vascular endothelium...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/0022-2828(91)90974-q
更新日期：1991-06-01 00:00:00
abstract：:We evaluated the time course of activation of endocardial endothelial cells and cardiomyocytes in adult rats with pressure overload induced by the abdominal aortic constriction. The silver staining technique for nucleolar organizer region was used to mark an increased transcriptional activity of the cells. An increase...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.1997.0484
更新日期：1997-09-01 00:00:00
abstract：:The modulating effects of Ca2+ on single K+ channel currents in canine heart sarcoplasmic reticulum were studied using a planar lipid bilayer technique. The open-state probability and the unitary open-state current both decreased gradually as the Ca2+ concentration was reduced from pCa 3 to pCa 7.5. Each single-channe...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.1994.1022
更新日期：1994-02-01 00:00:00
abstract：:Serine 727 (Ser727) phosphorylation of STAT3 plays a role in the regulation of mitochondrial respiration. This study aimed to test if zinc could regulate mitochondrial respiration through phosphorylation of STAT3 at Ser727 in the setting of ischemia/reperfusion in the heart. Under normoxic conditions, treatment of iso...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2018.03.019
更新日期：2018-05-01 00:00:00
abstract：:Phospholipase D (PLD) plays a central role in receptor-mediated breakdown of choline phospholipids and formation of phosphatidic acid (PA), an important regulator of cardiac function. However, specific mechanisms that regulate myocardial PLD activity remain largely unknown, particularly in the human heart. We hypothes...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2003.11.008
更新日期：2004-02-01 00:00:00
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journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/0022-2828(95)90022-5
更新日期：1995-09-01 00:00:00
abstract：:Heart and skeletal muscle cells rapidly lose potassium ions after withdrawal of oxygen. In myocardial ischemia, cellular release of potassium and interruption of extracellular washout produce a rapid and marked increase of extracellular K+ concentration. Harris et al. were the first to observe the coincidence of the K...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/s0022-2828(87)80608-9
更新日期：1987-10-01 00:00:00
abstract：:There is increasing evidence that reactive oxygen species (ROS) contribute to post-ischemic reperfusion injury, but determination of the specific ROS involved has proven elusive. In the present study electron paramagnetic resonance (EPR) spectroscopy was used in vitro to measure the relative quenching of singlet oxyge...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.1998.0850
更新日期：1999-01-01 00:00:00
abstract：:Current pharmacologic therapy for ischemic heart disease suffers multiple limitations such as compliance issues and side effects of medications. Revascularization procedures often end with need for repeat procedures. Patients remain symptomatic despite maximal medical therapy. Gene therapy offers an attractive alterna...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章,评审
doi：10.1016/j.yjmcc.2010.06.007
更新日期：2011-05-01 00:00:00
abstract：:Monoclonal antibodies (MAb) to myosin heavy chains were prepared from one adult human ventricular myocardium. Several of these MAb reacted by indirect immunofluorescence in a heterogenous way on cryostat transverse sections of fibers from human atrial myocardium, suggesting the presence of different forms of myosin wi...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/s0022-2828(85)80037-7
更新日期：1985-08-01 00:00:00
abstract：:The sulfonylurea receptor SUR is an ATP binding cassette (ABC) protein of the ABCC/MRP family. Unlike other ABC proteins, it has no intrinsic transport function, neither active nor passive, but associates with the potassium channel proteins Kir6.1 or Kir6.2 to form the ATP-sensitive potassium (K(ATP)) channel. Within ...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章,评审
doi：10.1016/j.yjmcc.2004.11.030
更新日期：2005-06-01 00:00:00
abstract：:Recent work has highlighted the role of NR4A receptors in atherosclerosis and inflammation. In vascular smooth muscle cell (VSMC) proliferation, however, NOR-1 (neuron-derived orphan receptor-1) exerts antagonistic effects to Nur77 and Nurr1. The aim of this study was to analyse the effect of NOR-1 in VSMC inflammator...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2014.12.015
更新日期：2015-03-01 00:00:00
abstract：:Human vascular connexins (Cx37, Cx40, Cx43, and Cx45) can form various types of gap junction channels to synchronize vasodilation/constriction to control local circulation. Most of our knowledge on heterotypic gap junctions of these vascular connexins was from studies on rodent connexins. In human vasculature, the sam...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2018.12.013
更新日期：2019-02-01 00:00:00
abstract：:Aging enhances cardiac injury during ischemia and reperfusion compared to the adult heart, including in the Fischer 344 rat model of aging (F344). In interfibrillar cardiac mitochondria obtained from the elderly F344 rat, the rate of oxidative phosphorylation and the activity of electron transport complex III is decre...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2009.03.007
更新日期：2009-06-01 00:00:00
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journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/s0022-2828(87)80395-4
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journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/0022-2828(90)90082-d
更新日期：1990-10-01 00:00:00
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journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/s0022-2828(85)80079-1
更新日期：1985-10-01 00:00:00
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journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/s0022-2828(95)90425-5
更新日期：1995-08-01 00:00:00
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journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.1998.0772
更新日期：1998-10-01 00:00:00
abstract：:The present study was undertaken to assess whether [32P]uptake and autoradiography could be used as an indicator of regional myocardial oxygen consumption. Rat hearts were perfused in the Langendorff mode with medium containing [32P]orthophosphate (32Pi) and the incorporation of label into ATP, perchloric acid-insolub...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.1993.1035
更新日期：1993-03-01 00:00:00
abstract：:The binding properties of [3H]U69593, a selective k-ligand, in rat heart homogenates were characterized by direct and displacement receptor binding assays. It was found that there are substantial specific [3H]U69593 binding sites in the rat heart. They were saturable, reversible and stereospecific. Both association an...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/0022-2828(91)90086-2
更新日期：1991-11-01 00:00:00
abstract：:Estrogen receptor alpha (ERalpha) is present in the heart consistent with estrogen-induced modulation of cardiac function by genomic and non-genomic mechanisms, and with estrogen-mediated cardioprotective effects. We show that, in heart from adult male rats, ERalpha is detected mainly as two distinct isoforms: (i) a a...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2006.05.022
更新日期：2006-09-01 00:00:00
abstract：:Inflammatory mediators have been implicated as a cause of reversible myocardial depression in septic shock. We previously reported that the release of lysozyme-c (Lmz-S) from leukocytes from the spleen or other organs contributes to myocardial dysfunction in Escherichia coli septic shock in dogs by binding to a cardia...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2005.06.009
更新日期：2005-10-01 00:00:00
abstract：:Cardiac tyhrotropin-releasing hormone (TRH) is overexpressed in the hypertrophied left ventricle (LV) of spontaneously hypertensive rats (SHR) and its inhibition prevents both hypertrophy and fibrosis. In a normal heart, the TRH increase induces fibrosis and hypertrophy opening the question of whether TRH could be a c...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2018.09.009
更新日期：2018-11-01 00:00:00
abstract：:Cardiac β-adrenergic receptors (β-AR) and Ca2+-Calmodulin dependent protein kinase (CaMKII) regulate both physiological and pathophysiological Ca2+ signaling. Elevated diastolic Ca2+ leak from the sarcoplasmic reticulum (SR) contributes to contractile dysfunction in heart failure and to arrhythmogenesis. β-AR activati...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2017.04.005
更新日期：2017-07-01 00:00:00
