Abstract:
AIMS:Class III antiarrhythmic agents exhibit reverse rate-dependent lengthening of the action potential duration (APD). In spite of the several theories developed so far to explain this reverse rate dependency (RRD), its mechanism has not yet been clarified. The aim of the present work was to further elucidate the mechanisms responsible for reverse rate-dependent drug effects. METHODS AND RESULTS:Action potentials were recorded from multicellular canine ventricular preparations and isolated cardiomyocytes, at cycle lengths (CLs) varying from 0.3 to 5 s, using conventional sharp microelectrodes. APD was either modified by applying inward and outward current pulses, or by superfusion of agents known to lengthen and shorten APD. Net membrane current (I(m)) was calculated from action potential waveforms. The hypothesis that RRD may be implicit in the relationship between I(m) and APD was tested by numerical modelling. Both drug-induced lengthening (by veratrine, BAY-K 8644, dofetilide, and BaCl(2)) and shortening (by lidocaine and nicorandil) of action potentials displayed RRD, i.e. changes in APD were greater at longer than at shorter CL. A similar dependency of effect on CL was found when repolarization was modified by injection of inward or outward current pulses. I(m) measured at various points during repolarization was inversely proportional to APD and to CL. Model simulations showed that RRD is expected as a consequence of the non-linearity of the relationship between I(m) and APD. CONCLUSION:RRD of APD modulation is shared, although with differences in magnitude, by interventions of very different nature. RRD can be interpreted as a consequence of the relationship between I(m) and APD and, as such, is expected in all species having positive APD-CL relationship. This implies that the development of agents prolonging APD with direct rate dependency, or even completely devoid of RRD, may be difficult to achieve.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Bányász T,Horváth B,Virág L,Bárándi L,Szentandrássy N,Harmati G,Magyar J,Marangoni S,Zaza A,Varró A,Nánási PPdoi
10.1093/cvr/cvp213subject
Has Abstractpub_date
2009-11-01 00:00:00pages
237-44issue
2eissn
0008-6363issn
1755-3245pii
cvp213journal_volume
84pub_type
杂志文章abstract:OBJECTIVE:The aim was to examine the effect of doxorubicin on spontaneous cyclic Ca2+ release from the sarcoplasmic reticulum of skinned fibres, as measured by isometric tension development in EGTA free, Ca2+ free solution. METHODS:Experiments were done on fragments of papillary muscles from the right ventricles of gu...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/26.4.371
更新日期:1992-04-01 00:00:00
abstract:OBJECTIVE:In the present study, we delivered vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) gene to a rabbit model of hind limb ischemia utilizing an ex vivo method of gene transfer, and evaluated the functional performance of the developed collateral vessels. METHOD:The left femor...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2003.10.003
更新日期:2004-01-01 00:00:00
abstract:OBJECTIVE:The aim was to evaluate in a minipig model of acute myocardial infarction the cardioprotection provided by the beta adrenoceptor blocking and vasodilating activities present in carvedilol; comparison was made to the pure beta adrenoceptor antagonist, propranolol. METHODS:Experiments were performed in 25 Yuca...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/26.5.518
更新日期:1992-05-01 00:00:00
abstract:AIMS:Coronary arteritis is a life-threatening complication that may arise in the acute stage of Kawasaki disease (KD), the leading cause of systemic vasculitis in childhood. Various microorganisms and molecular pathogens have been reported to cause KD. However, little is known about the key molecules that contribute to...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvz305
更新日期:2021-01-01 00:00:00
abstract:OBJECTIVE:Intercellular adhesion molecule (ICAM)-1 is an immunoglobulin-like cell adhesion molecule expressed by several cell types, including proliferating vascular smooth muscle cells (VSMC). Cross-linking ICAM-1 on the surface of different cell types has previously been shown to cause an increase in cellular activat...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(01)00207-3
更新日期:2001-06-01 00:00:00
abstract::STUDY OBJECTIVE - The aim of the study was to determine the changes in the beta adrenergic system induced by cardiac hypertrophy due to valvular aortic stenosis. DESIGN - Density of beta adrenoceptors, cardiac tissue noradrenalime concentrations, coronary blood flow (using radioactive microspheres), and haemodynamic v...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/24.1.65
更新日期:1990-01-01 00:00:00
abstract::Attempts were made to demonstrate release of vasoactive substances from the heart during coronary occlusion (for 60 min) and reperfusion (for 60 min), and to clarify the pathophysiological significance of them. Vasoactive substances were detected by superfusion of rabbit aortic and dog coronary arterial strips with gr...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/16.2.99
更新日期:1982-02-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to determine whether chronic beta-adrenergic receptor (beta-AR) stimulation induces proliferation of human cardiac fibroblasts and to investigate the mechanism(s) involved. METHODS AND RESULTS:In vitro cultures of human cardiac fibroblasts were established from biopsies of right atr...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(02)00729-0
更新日期:2003-03-01 00:00:00
abstract:BACKGROUND:Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligands have been shown to ameliorate a variety of inflammatory conditions. The present study tested the hypothesis that PPAR-gamma ligands reduce experimental autoimmune myocarditis (EAM) associated with inhibition of the expansion and activation...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(03)00457-7
更新日期:2003-09-01 00:00:00
abstract:OBJECTIVE:Oxidized low-density lipoproteins (ox-LDL) or their components suppress macrophage inflammatory response by down-regulating cytokine synthesis, nitric oxide synthase and inducible cyclooxygenase (Cox-2). This event is crucial for the pathophysiological process leading to the formation of atherosclerotic plaqu...
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
abstract:STUDY OBJECTIVE:The aim was to evaluate the thrombolytic efficacy of recombinant double chain tissue plasminogen activator (Duteplase, t-PA) given as a single intravenous bolus versus an infusion in a canine model of coronary arterial occlusion/reperfusion. DESIGN:Coronary arterial thrombi were induced by a copper coi...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/25.3.184
更新日期:1991-03-01 00:00:00
abstract:AIMS:The expression of PUMA (p53-up-regulated modulator of apoptosis), an apoptosis-regulating gene, increases during endoplasmic reticulum stress. The mechanisms by which cyclic stretch influences the regulation of PUMA in vascular smooth muscle cells (VSMCs) during apoptosis remain unclear. We hypothesized that cycli...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvr280
更新日期:2012-01-01 00:00:00
abstract:AIMS:Shock wave therapy (SWT) represents a clinically widely used angiogenic and thus regenerative approach for the treatment of ischaemic heart or limb disease. Despite promising results in preclinical and clinical trials, the exact mechanism of action remains unknown. Toll-like receptor 3, which is part of the innate...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvv272
更新日期:2016-02-01 00:00:00
abstract:OBJECTIVE:The mechanism of the protective effect of ischaemic preconditioning in the myocardium is not yet known. The aim of this study was to test the hypothesis that endogenous myocardial catecholamines may be mediators of preconditioning. METHODS:To test whether endogenous catecholamines are involved in preconditio...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
abstract:OBJECTIVE:Left ventricular assist devices (LVAD) have been used to 'bridge' patients with end-stage heart failure to transplantation. Although several reports have suggested that the native ventricular function recovers after long-term LVAD support, a process called 'reverse remodeling', the underlying biological mecha...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(01)00433-3
更新日期:2002-01-01 00:00:00
abstract:AIMS:Neointimal hyperplasia is a common feature of fibro-proliferative vascular disease and characterizes initial stages of atherosclerosis. Neointimal lesions mainly comprise smooth muscle-like cells. The presence of these lesions is related to local differences in shear stress. Neointimal cells may arise through migr...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvv175
更新日期:2015-12-01 00:00:00
abstract:AIMS:Thromboxane A2 (TXA2) induces platelet adhesion through thromboxane prostanoid (TP) receptor. Platelets contain many pro-angiogenic factors and are recruited to the site of vascular injury. However, the cellular and molecular mechanisms of platelet-dependent angiogenesis, especially the involvement of TP signallin...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvv139
更新日期:2015-09-01 00:00:00
abstract:STUDY OBJECTIVE:The aim of the study was to test an intermittent ECG synchronised suction device which was added to a coronary vein retroinfusion system (selective suction and retroinfusion = SSR) in order to transport oxygenated fluid more efficiently into ischaemic myocardium. DESIGN:The suction period preceding the...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/24.6.456
更新日期:1990-06-01 00:00:00
abstract::Acute occlusions of the proximal left circumflex coronary arteriovenous pedicle were performed in open chest anaesthetised dogs. Twenty eight dogs were randomly allocated to receive acebutolol (3 mg X kg-1 twice daily) or placebo given blindly by mouth for five days; a control group of 14 dogs without any pretreatment...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/20.10.721
更新日期:1986-10-01 00:00:00
abstract::Changes in left ventricular internal diameter resulting from increasing intrapericardial pressure induced by increasing the pericardial fluid volume were studied in closed chest, anaesthetized dogs. Left ventricular internal diameters were measured by placing an ultrasonic dimension catheter in the left ventricle at t...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/9.6.707
更新日期:1975-11-01 00:00:00
abstract::Functional studies in extrarenal non-epithelial cells such as smooth muscle cells and easily accessible human lymphocytes have demonstrated that aldosterone not only produces classical genomic effects, but also rapid non-genomic effects on transmembrane electrolyte movements. These involve the activation of the Na+/H+...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:
更新日期:1995-02-01 00:00:00
abstract:BACKGROUND:A recent genome-wide association study identified a susceptibility locus for atrial fibrillation at the KCNN3 gene. Since the KCNN3 gene encodes for a small conductance calcium-activated potassium channel, we hypothesized that overexpression of the SK3 channel increases susceptibility to cardiac arrhythmias....
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvt269
更新日期:2014-02-01 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::Severe sepsis and septic shock, which are among the most common causes of death in intensive care units worldwide, cause high morbidity, mortality, and social and economic costs. Therefore, developing successful therapies against sepsis is one of the most important challenges in critical care medicine. Death from sept...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvq317
更新日期:2011-02-15 00:00:00
abstract:OBJECTIVE:Activation of peroxisome proliferator-activated receptor alpha (PPARalpha) and PPARgamma plays beneficial roles in cardiovascular disorders such as atherosclerosis and heart reperfusion. Although PPARalpha and gamma have been documented to reduce oxidative stress in the vasculature and the heart, the role of ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2005.10.019
更新日期:2006-02-01 00:00:00
abstract::Postextrasystolic potentiation was studied by means of a catheter-tip manometer in patients with and without cardiomyopathy. The results imply that the enhancement of the left ventricular contraction is increased in patients with cardiomyopathy. ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/9.3.336
更新日期:1975-05-01 00:00:00
abstract::The cellular and molecular physiology and pathology of insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) are mostly studied and understood through the use of animal models. Fundamental differences between the IDDM and NIDDM animal models may help to explain the etiology beh...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(00)00025-0
更新日期:2000-06-01 00:00:00
abstract::Primary cardiomyopathy is an important cause of mortality in children and adults. Apart from inherited disorders of myocardial contractile and structural proteins, several defects of energy metabolism may cause cardiomyopathy. Most of the energy required for myocardial contraction is derived from aerobic metabolism. F...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(97)00141-7
更新日期:1997-08-01 00:00:00
abstract::The afterload dependency of relaxation rate was reappraised in isolated canine hearts both in isovolumic and isobaric contractions by using the reliable exponential method in which the asymptote LV pressure (P chi) is variable. This method provided a closer correlation (r = 0.999 +/- 0.001) between the measured LV pre...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/19.10.649
更新日期:1985-10-01 00:00:00
abstract:AIMS:For the majority of congenital heart diseases (CHDs), the full complexity of the causative molecular network, which is driven by genetic, epigenetic, and environmental factors, is yet to be elucidated. Epigenetic alterations are suggested to play a pivotal role in modulating the phenotypic expression of CHDs and t...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvw195
更新日期:2016-10-01 00:00:00