Abstract:
:Elevation of cytosolic sodium is thought to be correlated with an increase in force of contraction due to an activation of sodium-calcium exchange. We investigated the inotropic response mediated by the new sodium-channel activator BDF 9148 (0.01-100 mumol/l) on failing human myocardium. Force of contraction was studied using electrically driven human papillary muscle strips from moderately (NYHA II-III, mitral valve replacement) and terminally (NYHA IV, heart transplantation) failing hearts. We also investigated the effects in auricular trabeculae from non-failing hearts (aortocoronary bypass operation). Results were compared with inotropic responses to DPI 201-106 (DPI, 0.1-3 mumol/l), Ca2+ (1.8-15 mmol/l) and isoprenaline (0.001-1 mumol/l). Carbachol (100 mumol/l) and adenosine (1000 mumol/l) were examined in the presence of BDF 9148 and isoprenaline. Both sodium-channel activators, BDF 9148 and DPI 201-106, increased force of contraction in a dose-dependent manner in papillary muscle strips as well as in auricular trabeculae. BDF 9148 and DPI 201-106 were more effective (max. PIE NYHA II-III 1.6 +/- 0.2 mN, NYHA IV 5.9 +/- 0.7 mN, P less than 0.05) and more potent (EC50 (in mumol/l): NYHA IV 0.35, 0.19-0.66; NYHA II-III 1.85, 1.37-2.41) in terminally failing as compared to moderately failing left ventricular myocardium. Moreover, the positive inotropic effects of BDF 9148 were greater than those of DPI 201-106 in NYHA IV (max. PIE 2.7 +/- 0.3 mN, P less than 0.05). In NYHA IV, BDF 9148 was as effective as CA2+ (max. PIE 5.1 +/- 0.4 mN). In the same hearts, the positive inotropic effects of isoprenaline were reduced in NYHA IV (max. PIE 2.1 +/- 0.3 mN) compared to NYHA II-III (max. PIE 3.4 +/- 0.4 mN, P less than 0.05). Adenosine as well as carbachol did not affect the positive inotropic response of BDF 9148 or DPI 201-106 but reduced the effectiveness of isoprenaline (P less than 0.05). In myocardial membranes, BDF 9148 was 1000-fold less effective in competition experiments with 3H-ouabain than ouabain. We conclude that (1) sodium-channel activators may produce a significant cAMP-independent positive inotropic effect in left ventricular myocardium from failing human hearts; (2) the inotropic effect of sodium-channel activators were more potent and more effective in NYHA IV as compared to NYHA II-III. The degree of myocardial failure does not reduce the effectiveness of the sodium-channel activator BDF 9148.
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Schwinger RH,Böhm M,Mittmann C,La Rosée K,Erdmann Edoi
10.1016/0022-2828(91)90170-qkeywords:
subject
Has Abstractpub_date
1991-04-01 00:00:00pages
461-71issue
4eissn
0022-2828issn
1095-8584pii
0022-2828(91)90170-Qjournal_volume
23pub_type
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journal_title:Journal of molecular and cellular cardiology
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doi:10.1016/j.yjmcc.2013.10.021
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abstract::The effects of adenosine on myocardial substrate utilization were assessed in isolated Langendorff-perfused rat hearts. In unpaced hearts perfused at constant flow with insulin, adenosine inhibited oxidation of both glucose and palmitate with similar dose-dependency, without significant effects on effluent lactate+pyr...
journal_title:Journal of molecular and cellular cardiology
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journal_title:Journal of molecular and cellular cardiology
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journal_title:Journal of molecular and cellular cardiology
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doi:10.1016/j.yjmcc.2004.11.022
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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
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2012.06.019
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abstract::Understanding the process of Ca(2+)/Mg(2+)exchange during muscle excitation and relaxation is fundamental to elucidating the mechanism of Ca(2+)-regulated muscle contraction. During the resting phase, the C-domain of cardiac troponin C may be occupied by either Ca(2+)or Mg(2+). Here, complexes of recombinant cardiac t...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.2000.1174
更新日期:2000-08-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2016.08.009
更新日期:2016-10-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2011.10.001
更新日期:2012-04-01 00:00:00
abstract:BACKGROUND:Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) have great potential as a cell source for therapeutic applications such as regenerative medicine, disease modeling, drug screening, and toxicity testing. This potential is limited, however, by the immature state of the cardiomyocyte...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2014.04.005
更新日期:2014-07-01 00:00:00
abstract::Fibroblast growth factor receptor 1 (FGFR1) is the only high-affinity FGFR in the vertebrate myocardium. FGFR1 is a tyrosine kinase receptor and has a non-redundant role in proliferation and differentiation of cardiomyocytes during embryogenesis. Results presented here demonstrate that FGFR1 gene expression declines a...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2007.12.008
更新日期:2008-03-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2004.01.009
更新日期:2004-05-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2017.05.013
更新日期:2017-07-01 00:00:00
abstract::The importance of endogenous and exogenous estrogen levels to the development of cardiovascular disease in women in controversial. The purpose of our study was to examine the effect of estrogen on the development of hypertension, cardiac hypertrophy, ventricular function, and gene expression for atrial natriuretic pep...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1999.0985
更新日期:1999-08-01 00:00:00
abstract::Cardiac progenitor cells (CPCs) are a crucial source of cells in cardiac development and regeneration. However, reported CPCs are heterogeneous, and no gene has been identified to transiently mark undifferentiated CPCs throughout heart development. Here we show that Spalt-like gene 1 (Sall1), a zing-finger transcripti...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2016.02.008
更新日期:2016-03-01 00:00:00
abstract::The effect of alpha1-adrenergic stimulation on L-type Ca2+ current (ICa,L) in adult rat ventricular myocytes was investigated using three different methods of current recording. During conventional whole-cell recordings with 5 mm-BAPTA included in the pipette solution, phenylephrine (20 microM) did not increase ICa,L ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1998.0758
更新日期:1998-10-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(89)90828-6
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(92)93172-g
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.2002.2041
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
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abstract::Normal atrial conduction requires similar abundances and homogeneous/overlapping distributions of two connexins (Cx40 and Cx43). The remodeling of myocyte connections and altered electrical conduction associated with atrial fibrillation (AF) likely involves perturbations of these connexins. We conducted a comprehensiv...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2014.08.021
更新日期:2014-11-01 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
更新日期:1987-05-01 00:00:00
abstract::Micromolar concentrations of lipoic acid racemate added to a working rat heart during hypoxia have been previously found to improve aortic flow during subsequent reoxygenation. Since the R-form represents the naturally occurring form of lipoic acid, and the S-form does not reveal a positive influence on ATP synthesis ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(95)90012-8
更新日期:1995-09-01 00:00:00
abstract::Doxorubicin (DOX)-induced cardiotoxicity has been a well-known phenomenon to clinicians and scientists for decades; however, molecular mechanisms underlying DOX cardiotoxicity are still being uncovered. Although the majority of prior research have implicated nuclear and mitochondrial events to be an important etiologi...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2017.01.007
更新日期:2017-03-01 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::Connexin40 (Cx40) and connexin45 (Cx45) are involved in both cardiac morphogenesis and propagation of electrical activity. We found that Cx40/Cx45 double deficiency (Cx40(-/-)/Cx45(+/-)) causes a variety of cardiac defects leading to high mortality during embryonic development and at birth. The majority of Cx40(-/-)/C...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2006.07.005
更新日期:2006-11-01 00:00:00
abstract::Endothelial cells produce endothelin, a powerful vasoconstrictor. We report the release of additional vasoconstrictor material in conditional filtrate from freshly harvested cells, which we identified as leukotrienes by radioimmunoassay (RIA) and by high pressure liquid chromatography (HPLC). The material was collecte...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1993.1077
更新日期:1993-06-01 00:00:00
abstract::Although endothelial progenitor cells (EPCs) play a pivotal role in the endothelial repair following arterial injury and shear stress has a beneficial effect on EPCs, however, the molecular mechanism underlying the influence of EPCs on the endothelial integrity and the regulation of shear stress on the EPC signaling r...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2012.01.019
更新日期:2012-05-01 00:00:00