Abstract:
AIMS:Ivabradine (Iva) has shown beneficial structural and functional effects in clinical and experimental heart failure (HF), but its action in combination with mechanical unloading (MU), such as during treatment with left ventricular assist devices (LVAD), is unknown. The aim of this study was to investigate the effects of Iva during MU, in a rodent model of HF. METHODS AND RESULTS:We studied the chronic effects (4 weeks) of Iva (10 mg/kg/day) alone and in combination with MU [induced by heterotopic abdominal heart transplantation (HATx)] on whole-heart and cellular structure, function, and excitation-contraction (E-C) coupling in a rodent (rat) model of HF, 12 weeks post-left coronary artery (LCA) ligation. Effects of Iva were compared with those of β-blockade using metoprolol [(Met), 250 mg/kg/day]. Iva, but not Met, reversed myocardial fibrosis, alone and in combination with MU. MU-induced restoration of deranged E-C coupling was enhanced by Iva to a greater extent than Met: both Iva and Met enhanced the recovery of the Ca(2+) transient amplitude and the sarcoplasmic reticulum (SR) Ca(2+) content, but Iva alone maintained MU-induced normalization of L-type Ca(2+) current and t-tubule abnormalities. Met prevented MU-induced reduction in the myocardial size (myocardial atrophy); Iva had no effect on this parameter. CONCLUSION:Iva shows beneficial structural and E-C coupling effects during MU: Iva reverses myocardial fibrosis and enhances the restoration of deranged E-C coupling, displaying more beneficial effects than that of Met. These results suggest that Iva may prove effective in enhancing functional recovery in heart failure patients receiving LVAD therapy.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Navaratnarajah M,Ibrahim M,Siedlecka U,van Doorn C,Shah A,Gandhi A,Dias P,Sarathchandra P,Yacoub MH,Terracciano CMdoi
10.1093/cvr/cvs318subject
Has Abstractpub_date
2013-02-01 00:00:00pages
230-9issue
2eissn
0008-6363issn
1755-3245pii
cvs318journal_volume
97pub_type
杂志文章abstract:OBJECTIVE:In several cell types, proteasome inhibitors like carbobenzoxyl-leucinyl-leucinyl-leucinal (MG132) induce the 72 kDa heat shock protein (Hsp72) and exert cell protective effects. However, data in cardiomyocytes are currently lacking. METHODS AND RESULTS:We investigated the effects of MG132 in cultured neonat...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(02)00232-8
更新日期:2002-04-01 00:00:00
abstract:OBJECTIVE:We have previously demonstrated that nuclear factor kappa B (NFkappaB) activation is needed for the development of cardiac hypertrophy in vivo. NFkappaB is a downstream transcription factor in the Toll-like receptor (TLR)-mediated signaling pathway; therefore, we investigated a role of TLR4 in cardiac hypertr...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2005.05.025
更新日期:2005-11-01 00:00:00
abstract:OBJECTIVE:Recent studies indicate that endothelial type nitric oxide synthase (NOS3) modulates cardiac systolic and diastolic function and the inotropic responsiveness to beta-adrenergic agonists, and may affect myocardial oxygen consumption. Although NOS3 is a constitutive protein, its levels of expression can be modi...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(98)00059-5
更新日期:1998-06-01 00:00:00
abstract::Zero drift may be a cause of imprecision when micromanometer tipped catheters are used for intravascular pressure measurement over long periods of time. Drift of only a few mm Hg may represent a significant error when accurate recording of low vascular pressures is required. To overcome this problem a micromanometer t...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/23.2.152
更新日期:1989-02-01 00:00:00
abstract:OBJECTIVE:To investigate the possible mechanisms of the antiatherosclerotic effects of the angiotensin-converting enzyme (ACE) inhibitor, fosinopril, in apolipoprotein (apo) E deficient mice. METHODS:Apo E deficient (E0) mice at the age of 8 weeks received either placebo or a high dose (25 mg/kg/d) of fosinopril suppl...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00239-4
更新日期:1999-12-01 00:00:00
abstract:AIMS:Although increased Na(+)/Ca(2+) exchanger 1 (NCX1) expression is observed during heart failure (HF), the pathological role of NCX1 during the progression of HF remains unclear. We examined alterations of NCX1 expression and activity in hearts after transverse aortic constriction (TAC) surgery and explored whether ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvw113
更新日期:2016-09-01 00:00:00
abstract:OBJECTIVE:We investigated the efficacy of nicaraven in reducing myocardial as well as coronary endothelial preservation-reperfusion (P/R) injury. METHODS:In experiment I, isolated rat hearts were mounted on a Langendorff (L) apparatus to estimate the baseline cardiac function. Group 1, 8- and 12-h storage in histidine...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(96)00268-4
更新日期:1997-03-01 00:00:00
abstract:OBJECTIVE:The aim was to clarify the site in the coronary microcirculation that is dilated by an ATP sensitive potassium channel opener, levcromakalim, and to examine whether the magnitude of dilatation is size dependent. METHODS:Coronary arterial microvessels were observed through an intravital microscope equipped wi...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.12.1780
更新日期:1994-12-01 00:00:00
abstract:OBJECTIVES:Elevated systemic arterial blood pressure is associated with left ventricular hypertrophy and fibrosis. It has been suggested that both circulating and local myocardial renin-angiotensin systems play a role in mediating these responses. Here we describe the natural history of ventricular hypertrophy and fibr...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(00)00063-8
更新日期:2000-07-01 00:00:00
abstract:AIMS:The channel function of the cardiac ryanodine receptor (RyR2) is modulated by calmodulin (CaM). However, the involvement of CaM in aberrant Ca(2+) release in diseased hearts remains unclear. Here, we investigated the pathogenic role of defective CaM binding to the RyR2 in the channel dysfunction associated with he...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvs271
更新日期:2012-12-01 00:00:00
abstract:AIMS:It is well established that dysfunction of voltage-dependent ion channels results in arrhythmias and conduction disturbances in the foetal and adult heart. However, the involvement of voltage-insensitive cationic TRPC (transient receptor potential canonical) channels remains unclear. We assessed the hypothesis tha...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvr167
更新日期:2011-11-01 00:00:00
abstract:BACKGROUND:During reperfusion of ischaemic myocardium, Na+/H+ exchange promotes recovery from acidosis resulting in an accumulation of intracellular Na+. This leads to calcium overload via Na+/Ca2+ exchange and might result in cell necrosis contributing to reperfusion injury. METHODS AND RESULTS:We assessed whether HO...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1995-12-01 00:00:00
abstract:AIMS:Atherogenesis, evolution of plaque, and outcomes following endovascular intervention depend heavily on the unique vascular architecture of each individual. Patient-specific, multiscale models able to correlate changes in microscopic cellular responses with relevant macroscopic flow, and structural conditions may h...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvu124
更新日期:2014-07-01 00:00:00
abstract::The effect of circulation time on plasma high density lipoprotein cholesterol concentrations was investigated in 20 male Wistar rats injected with alcohol, stressed with lighting, or fed a high fat diet. Circulation time was measured during anaesthesia with a computerised dichromatic earpiece densitometer. Indocyanine...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/22.5.368
更新日期:1988-05-01 00:00:00
abstract::When the vagus nerves are stimulated with one burst of pulses per minute, but each burst is placed at a different time in the cardiac cycle, a "vagal effect curve" can be derived which displays the changes in cardiac cycle length (CCL) as a function of the elapsed time from the stimulus. This curve consists of a prima...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/18.2.75
更新日期:1984-02-01 00:00:00
abstract:AIMS:Notch signalling is essential for blood vessel formation. During angiogenesis, the Notch ligand DLL4 on the leading tip cell activates Notch receptors on the adjacent stalk cells. DLL4-Notch signalling is impaired by the Notch ligand JAG1 in endothelial cells. The Delta/Serrate/Lag2 (DSL) domain of the Notch ligan...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvv151
更新日期:2015-07-01 00:00:00
abstract:OBJECTIVE:Matrix metalloproteinase-9 (MMP-9) activity is up regulated in the heart subjected to ischemic insult. Whether increased MMP-9 activity contributes to acute myocardial injury after ischemia-reperfusion remains unknown. To investigate the role of MMP-9 in myocardial infarction, we utilized a MMP-9 knockout mou...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(02)00254-7
更新日期:2002-06-01 00:00:00
abstract:AIMS:Tungstate reduces blood pressure in experimental animal models of both hypertension and metabolic syndrome, although the underlying mechanisms are not fully understood. Given that the large-conductance voltage- and Ca(2+)-dependent K(+) (BK) channel is a key element in the control of arterial tone, our aim was to ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvs139
更新日期:2012-07-01 00:00:00
abstract:OBJECTIVES:Platelets contain numerous substances regulating angiogenic response. However, the regulatory role of platelets in blood vessel development remains to be elucidated. We investigated the comprehensive effect of platelets as a cellular system on angiogenesis. METHODS:The following approaches were applied: (a)...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2004.04.012
更新日期:2004-08-01 00:00:00
abstract:STUDY OBJECTIVE:The objectives were (a) to describe the effects of vasoactive drugs in normal rats upon cardiovascular function assessed by computing aortic haemodynamic power and input impedance, each separated into their component parts, and (b) to study the relationship between left ventricular pulsatile power outpu...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/25.11.923
更新日期:1991-11-01 00:00:00
abstract:OBJECTIVE:Polymorphonuclear leukocytes (PMN), retained in the microvascular bed, can contribute to postischemic myocardial reperfusion injury. Since a beneficial effect of ACE-inhibition on reperfusion injury has been reported, we investigated the impact of cilazaprilat on PMN dependent reperfusion injury in isolated g...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(97)00191-0
更新日期:1997-12-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(02)00437-6
更新日期:2002-08-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvr345
更新日期:2012-03-01 00:00:00
abstract:OBJECTIVE:R 75,231, a potent and specific nucleoside transport inhibitor, largely prevents cardiac damage and death in catecholamine challenged rabbits. The major biochemical effect of nucleoside transport inhibition in ischaemic and reperfused myocardium is a prolonged accumulation of adenosine. The cardioprotection b...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.1.111
更新日期:1993-01-01 00:00:00
abstract::The effects of both gradual and abrupt coronary occlusion on regional wall function (sonomicrometry) and left ventricular relaxation were studied in the intact dog heart. The ischaemic dysfunction observed in the two interventions as assessed by pressure-length loops showed considerably different patterns. The regiona...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/21.7.507
更新日期:1987-07-01 00:00:00
abstract::To improve assessment of ventricular function during cardiac catheterisation there should be available a continuous registration of stroke volume and cardiac output in addition to ventricular pressure. To obtain the desired volumetric quantities a catheter has been developed which measures changes in intraventricular ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/15.6.328
更新日期:1981-06-01 00:00:00
abstract:AIMS:Transforming growth factor-beta1 (TGF-beta1) is a multifunctional cytokine that contributes to pathogenic cardiac remodelling via mechanisms that involve oxidative stress. However, the direct impact of TGF-beta1 on contractile function of ventricular myocytes is incompletely understood. METHODS AND RESULTS:Reacti...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvm022
更新日期:2008-01-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(02)00236-5
更新日期:2002-04-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(97)00086-2
更新日期:1997-07-01 00:00:00
abstract:STUDY OBJECTIVE:The aim was to investigate the arrhythmogenic properties of several sympathomimetic amines and their antagonism by adrenergic blocking drugs. DESIGN:Arrhythmia was induced by the investigated drugs, injected intravenously: adrenaline (ADR); noradrenaline (NA); phenylephrine (PE); isoprenaline (IP); ter...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/24.9.754
更新日期:1990-09-01 00:00:00