Abstract:
PURPOSE:Dofetilide is class III antiarrhythmic agent which prolongs cardiac action potential duration because of selective inhibition of I (Kr), the rapid component of the delayed rectifier K(+) current. Although clinical studies reported on proarrhythmic risk associated with dofetilide treatment, the contributing electrophysiological mechanisms remain poorly understood. This study was designed to determine if dofetilide-induced proarrhythmia may be attributed to abnormalities in ventricular repolarization and refractoriness. METHODS:The monophasic action potential duration and effective refractory periods (ERP) were assessed at distinct epicardial and endocardial sites along with volume-conducted ECG recordings in isolated, perfused guinea-pig heart preparations. RESULTS:Dofetilide was found to produce the reverse rate-dependent prolongation of ventricular repolarization, increased the steepness of action potential duration rate adaptation, and amplified transepicardial variability in electrical restitution kinetics. Dofetilide also prolonged the T peak-to-end interval on ECG, and elicited a greater prolongation of endocardial than epicardial ERP, thereby increasing transmural dispersion of refractoriness. At epicardium, dofetilide prolonged action potential duration to a greater extent than ERP, thus extending the critical interval for ventricular re-excitation. This change was associated with triangulation of epicardial action potential because of greater dofetilide-induced prolonging effect at 90 % than 30 % repolarization. Premature ectopic beats and spontaneous short-lasting episodes of monomorphic ventricular tachycardia were observed in 44 % of dofetilide-treated heart preparations. CONCLUSIONS:Proarrhythmic potential of dofetilide in guinea-pig heart is attributed to steepened electrical restitution, increased transepicardial variability in electrical restitution kinetics, amplified transmural dispersion of refractoriness, increased critical interval for ventricular re-excitation, and triangulation of epicardial action potential.
journal_name
Cardiovasc Drugs Therjournal_title
Cardiovascular drugs and therapyauthors
Osadchii OEdoi
10.1007/s10557-012-6405-1subject
Has Abstractpub_date
2012-12-01 00:00:00pages
489-500issue
6eissn
0920-3206issn
1573-7241journal_volume
26pub_type
杂志文章abstract:PURPOSE:To investigate the protective effects of hydrogen sulfide (H(2)S) against chronic alcohol intake-induced left ventricular remodeling and explore the potential mechanisms involved. METHODS:Rats were randomly divided into 4 groups: alcohol group, NaHS group, alcohol + NaHS group, and control group. The echocardi...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-013-6441-5
更新日期:2013-06-01 00:00:00
abstract::Preconditioning and stunning are the chief adaptive changes induced in myocardium by a brief episode of reversible ischemia followed by arterial reperfusion. In the dog heart, both coexist for a period of at least 20 minutes of reperfusion, but after 120 minutes of reflow, preconditioning is much diminished, while stu...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF00053555
更新日期:1991-10-01 00:00:00
abstract:INTRODUCTION:Atrial dilatation is commonly associated with atrial fibrillation (AF), but the electrophysiological mechanisms and the implications for anti-arrhythmic therapy are poorly understood. In a model of acute stretch-related AF in isolated rabbit hearts, we evaluated the electrophysiological effects of three di...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-007-6001-y
更新日期:2007-02-01 00:00:00
abstract:INTRODUCTION:Several beta blocking drugs (BB) reduce mortality in systolic heart failure (LVSD). We have compared the initial response to introduction of carvedilol and bisoprolol during the standard dose titration protocols for each drug. METHODS:Approximately 31 unselected patients with stable LVSD were randomised t...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,随机对照试验
doi:10.1007/s10557-007-6055-x
更新日期:2007-12-01 00:00:00
abstract::During acute myocardial ischemia, passage of potassium ions across the sarcolemma to the extracellular space is a well-established phenomenon. A recent hypothesis is that the ATP-dependent potassium channel plays a role in contributing to the potassium loss. As the potassium loss starts while the overall level of ATP ...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF00877615
更新日期:1993-08-01 00:00:00
abstract:PURPOSE:Ranolazine (RAN) added to amiodarone (AMIO) has been shown to accelerate termination of postoperative atrial fibrillation (POAF) following coronary artery bypass surgery in patients without heart failure (HF). This study aimed to investigate if treatment efficacy with AMIO or AMIO + RAN differs between patients...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,随机对照试验
doi:10.1007/s10557-018-6832-8
更新日期:2018-12-01 00:00:00
abstract::The effects of administration of guava and papaya fruit (100 g/day), vegetables, and mustard oil (5 g/day) (group A); antioxidant vitamins C (50 mg/day) and E (30 mg/day), plus betacarotene (10 mg/day) (group B); a high-fat (5-10 g/day) (group C); or a low-fat (4-5 g/day) diet (group D) were compared over 24 diet week...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/BF00879869
更新日期:1995-12-01 00:00:00
abstract::True positive inotropy of enoximone is hard to prove clinically. It could increase the risk of myocardial ischemia when used in coronary artery disease (CAD). The analysis of the end-systolic pressure-volume relationship (ESPVR) as a load-independent parameter of the contractile left ventricular function (LVF) allows ...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/BF02018269
更新日期:1990-10-01 00:00:00
abstract:OBJECTIVE:Percutaneous vascular interventions lead inevitably to a destruction of the endothelial lining at the site of injury. There are conflicting data on the therapeutic benefit of hematopoietic growth factors aiming at mobilisation of circulating endothelial cells to accelerate the reendothelialisation process. Ai...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-008-6117-8
更新日期:2008-10-01 00:00:00
abstract:PURPOSE:Hypothyroidism (HT) is associated with accelerated atherosclerosis (AS). The efficacy of traditional strategies of hypothyroid AS remains controversial. Here, we aimed to deepen the understanding of the HT-induced acceleration of AS, to decrease the residual risk of coronary artery disease (CAD) and to find a n...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-020-06996-w
更新日期:2020-06-03 00:00:00
abstract::Vascular endothelium gene expression regulates blood-vessel wall interactions, vascular permeability, smooth muscle cell growth and tone. The possibility to introduce exogenous DNA or RNA sequences in endothelial cells represents a novel therapeutic approach of vascular disease. The aim of the work was to investigate ...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1023/a:1011154616992
更新日期:2001-01-01 00:00:00
abstract::Cholesterol plays an essential role in cell membrane synthesis and in cell growth and differentiation. In mammalian cells, cholesterol can be synthesized from acetate precursors or taken up from dietary or exogenous sources. The major catabolic route for disposal of cholesterol involves conversion into excretable bile...
journal_title:Cardiovascular drugs and therapy
pub_type: 社论,评审
doi:10.1007/BF00054556
更新日期:1992-04-01 00:00:00
abstract::In patients with hypertension persisting on combined diuretic and beta-blocker therapy, the effects of an additional 9-week therapy with a calcium antagonist (nifedipine) versus a classical arterial vasodilator (hydralazine) were compared for changes in blood pressure (BP), plasma catecholamines (n = 15), and left ven...
journal_title:Cardiovascular drugs and therapy
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF01857760
更新日期:1990-04-01 00:00:00
abstract:PURPOSE:Mechanical stretch is an arrhythmogenic factor found in situations of cardiac overload or dyssynchronic contraction. Ranolazine is an antianginal agent that inhibits the late Na (+) current and has been shown to exert a protective effect against arrhythmias. The present study aims to determine whether ranolazin...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-015-6587-4
更新日期:2015-06-01 00:00:00
abstract::The effects of oral zofenopril pretreatment were investigated in a chronic closed-chest pig model of ischemia and reperfusion. Pigs (25-35 kg) were pretreated orally with zofenopril (15 mg/day) on the 2 days prior to ischemia, which was evoked by the inflation of a catheter balloon in the left anterior descending coro...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/BF01856557
更新日期:1990-06-01 00:00:00
abstract::The effects of equipotent concentrations of diltiazem, verapamil, and nifedipine upon the accumulation of extracellular potassium [K+]out and the left ventricular pressure (LVP) were studied during global ischemia in isolated perfused rat hearts. Measurement of [K+]out and LVP were performed in two series of experimen...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/BF00143532
更新日期:1991-12-01 00:00:00
abstract:PURPOSE:The prevalence and consequences of prediabetic dysglycemia and undiagnosed diabetes is unknown in patients with heart failure (HF) and preserved ejection fraction (HFpEF) and has not been compared to heart failure and reduced ejection fraction (HFrEF). METHODS:We examined the prevalence and outcomes associated...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-017-6754-x
更新日期:2017-12-01 00:00:00
abstract:OBJECTIVES:To evaluate and compare the functional type and the degree of antagonism of the selective angiotensin II type 1 receptor blockers (ARB) losartan, EXP 3174 (the active metabolite of losartan), valsartan and candesartan in human internal mammary arteries. METHODS:Human internal mammary arteries were obtained ...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1023/a:1021729909456
更新日期:2002-07-01 00:00:00
abstract::Mivazerol, 3-[1(H-imidazol-4-yl)methyl]-2-hydroxybenzamide hydrochloride, is a selective alpha 2-adrenoceptor agonist designed for the prevention of myocardial infarction in perioperative patients. Because unintended hypothermia occurs frequently during surgery, we were interested, in this study, to examine the relati...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1023/a:1007762107360
更新日期:1997-12-01 00:00:00
abstract::Of 17 patients with mild to moderate essential hypertension, 8 showed echocardiographic evidence of left ventricular hypertrophy. Cardiac and renal function evaluated by glomerular filtration rate (GFR) were studied in all patients before and after 20 weeks of quinapril treatment. Systolic pressure decreased from 174....
journal_title:Cardiovascular drugs and therapy
pub_type: 临床试验,杂志文章
doi:10.1007/BF00877120
更新日期:1994-10-01 00:00:00
abstract::To further evaluate the significance of p38 MAPK as trigger or mediator in ischaemic preconditioning, anisomycin and SB 203580 were used to manipulate its activation status. Special attention was given to the concentration of the drugs and protocols used. The isolated perfused rat heart, subjected to either 25 min glo...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1023/a:1026116022552
更新日期:2003-05-01 00:00:00
abstract::One hundred thirteen patients undergoing cardiopulmonary bypass were randomly assigned to receive either bovine or porcine heparin. Heparin was infused at 4.5 mg/kg during bypass and administered at the lesser of 70 units/kg or 5000 units/dose at 12-hour intervals postoperatively. Platelet counts decreased to 45% of p...
journal_title:Cardiovascular drugs and therapy
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF01857644
更新日期:1990-02-01 00:00:00
abstract:PURPOSE:This study aimed to investigate the cost-effectiveness of low-dose rivaroxaban plus aspirin versus aspirin alone for patients with stable cardiovascular diseases in the Taiwan setting. METHODS:We constructed a Markov model to project the lifetime direct medical costs and quality-adjusted life-years of both the...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-020-07059-w
更新日期:2020-09-10 00:00:00
abstract:INTRODUCTION:Most circulating fatty acids are contained in lipoprotein triglycerides. For the heart to acquire these lipids, they must be broken down into free fatty acids via the enzyme lipoprotein lipase (LpL). Although it has long been known that hearts primarily use esterified fatty acids as fuel, different sources...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/s10557-006-0633-1
更新日期:2006-12-01 00:00:00
abstract::The place of digoxin in the pediatric cardiologist's armamentarium remains uncertain. As an antiarrhythmic, its use in the Wolff-Parkinson-White syndrome is obsolete, but it remains useful in the treatment of the chronic atrial fibrillation seen in some patients postoperatively and in children with dilated cardiomyopa...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF01881525
更新日期:1989-03-01 00:00:00
abstract::In animal models, calcium antagonists (Ca-A) administered before ischemia and reperfusion reduced myocardial necrosis, attenuated postischemic contractile dysfunction, and reduced tissue calcium. In 753 patients with acute myocardial infarction (AMI), we examined if use of Ca-A at the onset of symptoms (n = 127 patien...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1023/a:1007727518684
更新日期:1997-09-01 00:00:00
abstract::Despite continuous advances in myocardial revascularization procedures and intracoronary devices, patients with ischemic heart disease (IHD) still experience worse prognosis and poor quality of life (QoL). Indeed, chronic stable angina (CSA) is a common disease with a large burden on healthcare costs. Traditionally, C...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/s10557-016-6677-y
更新日期:2016-08-01 00:00:00
abstract:PURPOSE:Treatment of atherosclerotic rabbits with intravenous methotrexate or etoposide carried in lipid nanoemulsions (LDE) markedly reduced the lesions in the aorta. Here, the combined treatment with LDE-methotrexate and LDE-etoposide was investigated aiming to increase the anti-atherosclerosis effect. METHODS:Thirt...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-014-6566-1
更新日期:2015-02-01 00:00:00
abstract::Pulmonary arterial hypertension (PAH) is a group of diseases characterized by a progressive increase of pulmonary vascular resistance (PVR), initially due to abnormal pulmonary vasoconstriction in response to endothelial injury. Recent studies have here confirmed the prominent role of endothelin (ET)-1 in vasoconstric...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/s10557-015-6605-6
更新日期:2015-01-01 00:00:00
abstract::Although torsades de pointes is not a tightly demarcated entity, the diagnosis has important clinical implications. The concept should be retained. ...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/BF03029821
更新日期:1991-02-01 00:00:00