Abstract:
:BACKGROUND: The tendency for the electrophysiologic effect of class III antiarrhythmic agents (action potential prolongation) to be diminished at faster heart rates represents a major drawback of this class of drug and is usually referred to as "reverse use dependence." A novel class III agent, MS-551, has recently been reported to exhibit less reverse use dependence than E-4031. We set out to investigate whether this observation may be due to differential blockade of the inward rectifier current (i(K1)) by these drugs. METHODS AND RESULTS: We recorded i(K1) using single channel methods and cell attached patch configurations, with standard patch clamp technology. Neither E-4031 nor racemic sotalol in concentrations up to 100 µM had any significant effect on the open probability or kinetics of i(K1) without altering the single-channel conductance. Openings to subconductance levels were abolished in three of six patches in which they had been frequently present in the absence of drug. MS-551 had no effect on mean channel open time but increased the slower component of the closed time. CONCLUSIONS: MS-551, unlike E-4031 and sotalol, appears to produce significant blockade of the inwardly rectifying potassium channel at clinically relevant concentrations. We propose that this might provide a partial explanation for the observed differences in their response to rate changes.
journal_name
J Cardiovasc Pharmacol Therjournal_title
Journal of cardiovascular pharmacology and therapeuticsauthors
Nakaya Y,Martin DK,Campbell TJdoi
10.1177/107424849700200105keywords:
subject
Has Abstractpub_date
1997-01-01 00:00:00pages
39-46issue
1eissn
1074-2484issn
1940-4034pii
S1074248497000035journal_volume
2pub_type
杂志文章abstract:PURPOSE:Methotrexate is an anti-inflammatory drug that has been shown to have anti-ischemic effects. Our aim was to evaluate if methotrexate could reduce infarct size in patients with ST-segment elevation myocardial infarction (STEMI). METHODS:We randomly assigned patients with STEMI to receive either methotrexate or ...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1177/1074248417699884
更新日期:2017-11-01 00:00:00
abstract::The existing clinical studies on remote ischemic preconditioning in patients undergoing cardiovascular surgery are critically reviewed, with a focus on infarct size reduction and clinical outcome as end points. Confounders, notably the use of propofol anesthesia are identified. The need for better designed trials with...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章,评审
doi:10.1177/1074248416687874
更新日期:2017-07-01 00:00:00
abstract::Homing of cardiac myosin-specific CD4-positive T cells into the myocardium is the initial pathologic event of experimental autoimmune myocarditis (EAM). Subsequently, various bystander inflammatory cells are recruited into the myocardium crossing vascular endothelial cell walls. Sulfated polysaccharide fucoidan binds ...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/1074248410378751
更新日期:2011-03-01 00:00:00
abstract::BACKGROUND: The effects of sotalol on the 24-hour profile of the QT interval relative to that of the heart rate (HR) may be helpful in determining the time course of the drug's action in controlling cardiac arhythmias. This has not been previously determined. Thus, the objective of the current study was to evaluate th...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/107424849900400104
更新日期:1999-01-01 00:00:00
abstract::Pulmonary arterial hypertension (PAH) is a progressive disease, which can be potentially fatal. The management of a complex disease like PAH requires a multidisciplinary approach from a team consisting of physicians, nurses, social workers, and pharmacists. Adherence to PAH-specific therapy is one of the key factors i...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章,评审
doi:10.1177/1074248419877409
更新日期:2020-03-01 00:00:00
abstract::The presenting signs of osteogenic osteosarcoma are commonly pain, local swelling, local warmth, pathologic fracture, and metastatic disease. Deep venous metastasis of osteoblastic osteosarcoma is most often a postmortem diagnosis. This paper describes the case of a previously healthy 18-year-old woman who presented w...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/107424840300800408
更新日期:2003-12-01 00:00:00
abstract::BACKGROUND: In recent years, there has been an increasing use of antiarrhythmic drugs that act predominantly by prolonging myocardial repolarization. An inevitable electrophysiologic consequence of these drugs is the development of torsade de pointes as a proarrhythmic reaction. Both intravenous lidocaine and magnesiu...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/107424849700200206
更新日期:1997-04-01 00:00:00
abstract::Recently, cyclooxygenase-2 (COX-2) inhibitors (coxibs), a class of drugs intended to be painkillers, have created unprecedented controversy because of their cardiovascular risk profile. The controversy has affected the patients, health-care providers, the Food and Drug Administration, and the manufacturers of these ag...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章,评审
doi:10.1177/107424840501000203
更新日期:2005-06-01 00:00:00
abstract::BACKGROUND: Micropuncture studies were performed to determine the intrarenal hemodynamic effects of two conventional antihypertensive agents, hydrochlorothiazide (HCTZ) and hydralazine (HYDR) alone and in combination. METHODS AND RESULTS: Male spontaneously hypertensive and normotensive Wistar Kyoto rats (19 weeks old...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/107424849600100109
更新日期:1996-01-01 00:00:00
abstract:BACKGROUND:Hypertension is a major cause of death and morbidity worldwide and is increasing in prevalence. The Renin-angiotensin system (RAS) is the most common mechanism involved in the pathophysiology of hypertension. Understanding the mechanism of the pathophysiologic processes will help direct potential therapeutic...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/1074248419838503
更新日期:2019-09-01 00:00:00
abstract:BACKGROUND:Brief periods of reocclusion (postconditioning) during early reperfusion reduce myocardial infarct size. Whether postconditioning has an effect on lethal ventricular arrhythmias independent of infarction in an in-vivo regional ischemia model is unknown. The purpose of this study was to determine if postcondi...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/107424840601100105
更新日期:2006-03-01 00:00:00
abstract:INTRODUCTION:Angiotensin converting enzyme inhibitors (ACEIs) are widely prescribed medications. A recent British study reported a 14% increased risk of lung cancer with ACEI versus angiotensin receptor blocker (ARB) prescriptions, and risk increased with longer use. We sought to validate this observation. METHODS:We ...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/1074248420987054
更新日期:2021-01-29 00:00:00
abstract::The primary effect of ischemia is reduced aerobic adenosine triphosphate (ATP) formation in mitochondria. This triggers accelerated glycolysis and reduced cell pH, Ca(2+) accumulation, K(+) efflux, adenosine formation, and the clinical signs of ischemia: chest pain and a shift in the ST segment. Traditional therapies ...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章,评审
doi:10.1177/107424840400900104
更新日期:2004-09-01 00:00:00
abstract:BACKGROUND:We hypothesized that the cardioprotective effect of angiotensin II (AngII) type 1 receptor (AT(1)R) blockade during in vivo ischemia-reperfusion (IR) might be associated with an increase in AngII type 2 receptor (AT(2)R) protein, as well as 1,4,5-inositol trisphosphate type 2 receptor (IP(3)R) and protein ki...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1054/JCPT.2000.19245
更新日期:2000-10-01 00:00:00
abstract::Catestatin (CST), which is emerging as a novel cardiac modulator, can protect the heart against excessive sympathetic drive in hypertensive cardiomyopathy. The aim of this study is to investigate whether exogenous CST decreases excessive cardiac sympathetic drive and improves autonomic function and exerts cardioprotec...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/1074248416628676
更新日期:2016-11-01 00:00:00
abstract:BACKGROUND:Fluvastatin is an inhibitor of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, effectively lowering serum cholesterol concentrations. A high-performance liquid chromatography (HPLC) assay was developed that determined the pharmacokinetics of fluvastatin in healthy individuals after administrat...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 临床试验,杂志文章
doi:10.1177/107424840100600205
更新日期:2001-04-01 00:00:00
abstract::Platelets are key mediators in the pathophysiology of atherothrombotic disease. Inappropriate platelet activation can lead to thrombosis and ischemic events. Platelet function testing has been used to monitor patient response to antiplatelet therapy. Variability in response to antiplatelet therapy may be due in part t...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章,评审
doi:10.1177/1074248409339309
更新日期:2009-09-01 00:00:00
abstract:BACKGROUND:The administration of aspirin is traditionally discontinued prior to coronary artery bypass grafting (CABG), given a potential risk of excessive postoperative bleeding. Few studies have previously suggested the benefits of continuing aspirin until the time of surgery. The primary aim of this review is to eva...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章,meta分析,评审
doi:10.1177/1074248413509026
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:epidemiologic studies indicate that elevated heart rate (HR) is an independent risk factor for mortality and morbidity in patients (pts) with chronic heart failure (CHF). Clinical trials with β-blockers suggest that HR reduction is an important mechanism of their benefit in pts with stable CHF. Pharmacologic...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1177/1074248410370326
更新日期:2010-12-01 00:00:00
abstract::Postischemic accumulation of intracellular Na+ promotes calcium overload and contributes to cellular necrosis. Cardioprotection afforded by pharmacologic blockade of the sodium-hydrogen exchanger subtype 1 (NHE1) is thought to be more remarkable than that obtained by ischemic conditioning (IC). The window of protectio...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/1074248418755120
更新日期:2018-05-01 00:00:00
abstract:OBJECTIVE:Acute lung injury is a common complication after cardiopulmonary bypass (CPB). Oxidative damage greatly impacts CPB-induced lung ischemic pathogenesis and may represent a target for treatment. We aimed to investigate whether curcumin upregulates heme oxygenase 1 (HO-1) expression and ameliorates lung injury i...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/1074248412442002
更新日期:2012-12-01 00:00:00
abstract:BACKGROUND:Myocardial infarction causes the acidification of the cellular environment and the resultant acidosis maybe arrhythmogenic. The effect of acidosis on the action of antiarrhythmic drugs, an important issue in the antiarrhythmic drug therapy after myocardial infarction, remains to be studied. METHODS:To evalu...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/107424840501000108
更新日期:2005-03-01 00:00:00
abstract::Dofetilide is a class III antiarrhythmic agent approved by the Food and Drug Administration for the conversion of atrial fibrillation and atrial flutter and maintenance of sinus rhythm in symptomatic patients with persistent arrhythmia. Drug trials showed neutral mortality in post-myocardial infarction patients and th...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章,评审
doi:10.1177/1074248418784288
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) were recently shown to be capable of electromechanical integration following direct injection into intact or recently injured guinea pig hearts, and hESC-CM transplantation in recently injured hearts correlated with improvements in contractile funct...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/1074248413520344
更新日期:2014-07-01 00:00:00
abstract::BACKGROUND: Circulating cells influence myocardial function during ischemia and reperfusion, (eg, neutrophils exacerbate, and platelets protect the myocardium from deterioration). This study was designed to determine the role of red blood cells on myocardial function following ischemia and reperfusion in isolated rat ...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/107424849600100405
更新日期:1996-10-01 00:00:00
abstract:BACKGROUND:Allogeneic cardiosphere-derived cells (CDCs) exert cardioprotective effects when administered intracoronarily after reperfusion in animal models of acute myocardial infarction (AMI). The "no-reflow" phenomenon develops rapidly post-reperfusion and may undermine the efficacy of cell therapy, due to poor cell ...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/1074248420941672
更新日期:2021-01-01 00:00:00
abstract:OBJECTIVE:To describe major events at follow up in octogenarian patients with atrial fibrillation (AF) according to anticoagulant treatment: direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs). METHODS:A total of 578 anticoagulated patients aged ≥80 years with AF were included in a prospective, obse...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章,多中心研究
doi:10.1177/1074248420916316
更新日期:2020-07-01 00:00:00
abstract:BACKGROUND:Patients with coronary artery disease (CAD) should be treated with statins to attain very low cholesterol levels, in order to reduce cardiovascular adverse events. More than 70% of these patients do not reach the appropriate cholesterol goal despite moderate statin doses. However, it is not known whether the...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1177/1074248413489771
更新日期:2013-09-01 00:00:00
abstract::BACKGROUND: Conventional microelectrode techniques were used to compare the concentration-dependent effects of vesnarinone (0.1-100 µM) and amrinone (1 µM-1 mM) on action potential duration (APD) and developed force in both isolated dog ventricular trabeculae and Purkinje strands. METHODS AND RESULTS: Both drugs incre...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/107424849600100207
更新日期:1996-04-01 00:00:00
abstract:BACKGROUND:Overexpression of the L-type voltage-dependent calcium channel alpha(1C)-subunit (L-VDCC OE) in transgenic mice results in adaptive hypertrophy followed by a maladaptive phase associated with a decrease in sarcoplasmic reticulum adenosine triphosphatase (SERCA)2a expression at 8 to 10 months of age. Overexpr...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/107424840501000404
更新日期:2005-12-01 00:00:00