Abstract:
:The effects of a newly synthesized antiarrhythmic agent, TYB-3823 on the transmembrane action potential were examined in isolated papillary muscles of guinea pig. TYB-3823 (3 x 10(-6)-3 x 10(-5)M) caused a dose-dependent decrease in the maximum upstroke velocity (Vmax) and a shortening of action potential duration (APD). In the presence of TYB-3823, trains of stimuli at rates greater than or equal to 0.2 Hz led to an exponential decline in Vmax. This use-dependent block was enhanced at higher stimulation frequency. The time constant for the recovery of Vmax from the use-dependent block was 12.6-13.4 s. The curves relating membrane potential and Vmax were shifted by TYB-3823 (3 x 10(-5)M) to the direction of more negative potentials (5.7 mV). In preparations treated with TYB-3823 (10(-5)-3 x 10(-5) M), the Vmax of test action potentials preceded by conditioning clamp pulses to 0 mV was progressively decreased by increasing the duration of a single clamp pulse or by increasing the number of multiple brief clamp pulses. These findings suggest that TYB-3823 has use- and voltage-dependent inhibitory action on the fast sodium channel by binding to the channel during its activated and inactivated states, and that the unbinding rate of the drug from the channel is very slow. Such characteristics of sodium channel block in combination with APD shortening effect would provide unique antiarrhythmic activities of this substance.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Kodama I,Morimoto M,Toyama J,Shibata Ssubject
Has Abstractpub_date
1989-04-01 00:00:00pages
616-23issue
4eissn
0160-2446issn
1533-4023journal_volume
13pub_type
杂志文章abstract::21-Aminosteroids are a group of new synthetic compounds developed as antiperoxidants. Although several studies have demonstrated their cardioprotective properties in acute ischemic models, none has assessed their long-term benefits after chronic myocardial infarction. In this investigation, we examined the cardioprote...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199912000-00013
更新日期:1999-12-01 00:00:00
abstract::The purpose of this study was to determine whether there are differences in the restoration of endothelial function by angiotensin-converting enzyme inhibition based on the severity of hypertension. Forearm blood flow (FBF) was measured in 69 patients with essential hypertension (mild, n = 23; moderate, n = 29; and se...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00005344-200205000-00007
更新日期:2002-05-01 00:00:00
abstract::The electrophysiologic and antiarrhythmic effects of oral and intravenous UM424 were studied in canine models of acute and chronic myocardial injury. In the first phase of this study, reentrant ventricular tachyarrhythmias and/or ventricular fibrillation were initiated by programmed electrical stimulation techniques i...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198503000-00001
更新日期:1985-03-01 00:00:00
abstract::To assess efficacy and side effects during chronic oral therapy, we studied the effect of ketanserin (Kn) in 17 hypertensive patients for a period up to 1 year. Ketanserin controlled blood pressure satisfactorily in 25%, in part in 50% and had little or no effect in 25%. Reduction in diastolic pressure equalled that i...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00005344-198500077-00043
更新日期:1985-01-01 00:00:00
abstract::We previously showed that rat and cow blood vessels contain arginine vasopressin (AVP) of local origin. In the present study, to investigate potential roles for this locally produced peptide, we examined the effects of AVP on growth of cultured vascular endothelial and smooth muscle cells (EC, SMC). Treatment of cultu...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199503000-00004
更新日期:1995-03-01 00:00:00
abstract::To determine if combinations of mexiletine and sotalol retain Class I and III electrophysiologic actions, using standard microelectrode techniques, we examined the electrophysiologic effects on canine Purkinje fibers of solutions of mexiletine (3.1-100 microM), sotalol (3.1-400 microM), and combinations of the two dru...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198809000-00005
更新日期:1988-09-01 00:00:00
abstract:BACKGROUND:Guanfu base A (GFA) and Guanfu base G (GFG) are chemicals isolated from Aconitum coreanum. The potassium channel encoded by the human ether-a-go-go related gene (HERG) plays an important role in repolarization of the cardiac action potential. The purpose of the present study was to investigate the effects of...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e318236e380
更新日期:2012-01-01 00:00:00
abstract::The therapeutic strategy of heart rate control for atrial fibrillation (AF) is undergoing a renaissance since several recent randomized trials demonstrated clear advantages over the rhythm control for many patients. Heart rate control for AF is hampered, however, by a dearth of information relating target heart rates ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/FJC.0b013e31816d5f49
更新日期:2008-07-01 00:00:00
abstract::Salusin-alpha and salusin-beta are newly identified bioactive peptides with hemodynamic and mitogenic activities. Recent studies have shown that salusins improve calcium uptake and protein synthesis in neonatal rat cardiomyocytes, suggesting that salusins may be regulatory factors for myocardial growth and hypertrophy...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/01.fjc.0000242059.89430.ac
更新日期:2006-08-01 00:00:00
abstract::Angiotensin II, bradykinin, and substance P are powerful vasoconstrictors of venous smooth muscle. In this report, we have characterized the receptors and the cellular mechanisms of these vasoactive peptides on a new isolated smooth muscle preparation, the rabbit vena cava. Receptors were characterized using agonists ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199109000-00013
更新日期:1991-09-01 00:00:00
abstract::We examined the electromechanical effects of two class III antiarrhythmic agents, dofetilide (UK-68,798) and D-sotalol, in acidic myocardium. Right ventricular papillary muscle preparations isolated from guinea pigs were divided into three groups (n = 6 per group): (a) drug-free, (b) dofetilide (10 nM), and (c) D-sota...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199212000-00007
更新日期:1992-12-01 00:00:00
abstract::We briefly review and compare the current knowledge of growth mechanisms for the mitogenic response of endothelial cells and smooth-muscle cells to injury. For the endothelium, this focuses on the evidence that growth control involves two components: an endogenous inhibition mechanism, which can be overcome either by ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/00005344-199321001-00007
更新日期:1993-01-01 00:00:00
abstract::Left coronary artery ligations or sham operations were performed on pentobarbitone-anesthetized rats. The rats were sacrificed at various times after artery occlusion or sham operation and the creatine kinase (CK), potassium (K+), and noradrenaline (NA) content was determined in the left and right ventricular myocardi...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1981-07-01 00:00:00
abstract::Endogenous as well as synthetic cannabinoids have potent vasodilatory actions in a variety of vascular preparations. Their precise mechanism of action is as yet unclear, but several studies point to the activation of type 1 vanilloid (TRPV1) receptors on primary afferent perivascular nerves, stimulating the release of...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/01.fjc.0000205053.53946.10
更新日期:2006-02-01 00:00:00
abstract::In this study, we examined glyceryl trinitrate (GTN) biotransformation and cyclic GMP elevation in vascular smooth muscle before onset of GTN-induced relaxation. Isolated rabbit aortic strips (RAS) and strips of bovine pulmonary artery (BPA) and bovine pulmonary vein (BPV) were contracted submaximally and incubated wi...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199005000-00005
更新日期:1990-05-01 00:00:00
abstract:AIMS:To determine whether short-term treatment with trimetazidine (TMZ), an antiischemic agent that directly inhibits fatty acid oxidation and results in stimulation of glucose oxidation, may improve myocardial perfusion and left ventricular systolic function in diabetic patients with ischemic cardiomyopathy. METHODS ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1097/FJC.0b013e31817bdd66
更新日期:2008-06-01 00:00:00
abstract::We investigated the effects of endothelin (ET) and thrombin on the production of interleukin 6 (IL-6) in human umbilical vein endothelial cells (HUVECs). ET-1 increased IL-6 production twofold in HUVECs incubated for 18 h with 10(-10) M ET-1. Thrombin also significantly increased IL-6 production. However, stimulation ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
abstract::The in vivo renal microvascular effects of three antihypertensive drugs: nitrendipine, a calcium entry blocker, and two direct-acting vasodilator agents, hydralazine and minoxidil, were compared. The dilator responses of pre- and postglomerular vessels were directly observed after the topical or intravenous administra...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1987-01-01 00:00:00
abstract::Recently, we provided in vitro and in vivo evidence that several vastatins with different potencies decrease arterial smooth-muscle cell (SMC) proliferation independently of their hypocholesterolemic properties. In this study, the in vivo dose-dependent antiproliferative activity of fluvastatin on neointimal formation...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
abstract::Neonatal exposure to a selective serotonin reuptake inhibitor (SSRI) leads to decreased left ventricular volumes and sympathetic activation in adult mice. We hypothesized this neonatal SSRI exposure-induced small left heart syndrome would increase post-myocardial infarction (MI) morbidity and mortality. C57BL/6 mice r...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e3182a4db90
更新日期:2013-11-01 00:00:00
abstract::Possible enhancement by free fatty acids (FFA) of the arrhythmogenic actions of ouabain was studied in rabbits. The mean dose of ouabain required for inducing ventricular tachycardia or fibrillation in conscious animals was significantly lowered by intravenous injection of 5 ml of a 20% fat emulsion (Lipofundin), whic...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198005000-00010
更新日期:1980-01-01 00:00:00
abstract::Populations with a high sodium intake have a high prevalence of hypertension and a high mortality and morbidity due to cerebrovascular disease. Within populations, however, it is very difficult to demonstrate a significant correlation between sodium intake and blood pressure. Experimental evidence exists demonstrating...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198400061-00030
更新日期:1984-01-01 00:00:00
abstract::Anakinra is a recombinant human interleukin 1 receptor antagonist that competes and blocks the biologic effects of interleukin 1, reducing systemic inflammatory responses. In the 2015 guidelines for the diagnosis and management of pericardial diseases of the European Society of Cardiology, anakinra was established as ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/FJC.0000000000000839
更新日期:2020-07-01 00:00:00
abstract::The formation of bone occurs via a series of events that are regulated by various hormones and cytokines. We previously reported that endothelin (ET) inhibits the mineralization by osteoblastic cells and natriuretic peptide (NP) promotes osteoblastic differentiation. Therefore, we attempted to identify the genes induc...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200036051-00084
更新日期:2000-11-01 00:00:00
abstract:PURPOSE:Roscovitine (Rosc) is a selective inhibitor of cyclin-dependent kinases (CDKs) and a promising therapy for various cancers. However, limited information is available on the biological significance of Rosc in vascular smooth muscle cells (VSMCs), the cell type critical for the development of proliferative vascul...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000453
更新日期:2017-03-01 00:00:00
abstract::Stroke is a major clinical problem in hypertension. Cerebral hemorrhage has become considerably less frequent since treatment of hypertension has become more widely used. Antihypertensive treatment has also reduced the incidence of lacunar stroke, which is a result of hypertensive vascular disease of small arteries. C...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1990-01-01 00:00:00
abstract::Using constant infusion technique and a water-loading procedure, we investigated renal hemodynamic and excretional variables in 15 essential hypertensive patients [diastolic blood pressure (DBP) 102 +/- 10 mm Hg] after 3 weeks of placebo and after 16 weeks of treatment with a postjunctional alpha 1-adrenoceptor-antago...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1097/00005344-199209000-00015
更新日期:1992-09-01 00:00:00
abstract::Metformin has been used for the treatment of some metabolic diseases during gestation and the beneficial effects of metformin to the vascular system have been described in diabetic and obese animal models. Nevertheless, the long-term consequences to the vascular system of offsprings maternally exposed to metformin hav...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000520
更新日期:2017-11-01 00:00:00
abstract::Arrhythmias occur 24 h after occlusion of the left anterior descending (LAD) coronary artery in the canine heart and have been attributed to the abnormal spontaneous activity in subendocardial Purkinje fibers, which are markedly depolarized. The major current underlying normal automaticity in these fibers is i(f). Alt...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199705000-00015
更新日期:1997-05-01 00:00:00
abstract:BACKGROUND:The present study has been designed to investigate the effect of sodium cromoglycate and ketotifen, mast cell stabilizers in hyperhomocysteinemia-induced cardiac hypertrophy in rats. METHODS:Rats were administered L-methionine (1.7 g/kg/day PO) for 8 weeks to produce hyperhomocysteinemia. Sodium cromoglycat...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e31817ae60f
更新日期:2008-06-01 00:00:00