Abstract:
:Pinacidil is one of a number of new antihypertensive agents possessing an action that involves an enhanced potassium efflux in cardiac and vascular smooth muscle. An associated feature of pinacidil is a shortening of the cardiac action potential duration, which may constitute a potentially proarrhythmic effect. The present study evaluated pinacidil (0.3 mg/kg/h i.v. for 6 h) on the postinfarcted canine heart in a subset of dogs unresponsive to programmed electrical stimulation during the subacute phase of anterior myocardial infarction, and known to be at low risk of ventricular fibrillation in response to acute posterolateral ischemia. Results were compared with a comparable control group of vehicle-treated, noninducible animals. Nonsustained ventricular tachyarrhythmia developed in 2 of 15 pinacidil-treated animals as compared to the initiation of ventricular tachycardia in 1 of 16 postinfarcted hearts (p = 0.96) in the control group. Thus, pinacidil did not alter the responsiveness of the postinfarcted heart with respect to the electrical induction of tachyarrhythmias. The subsequent development of an acute ischemic event at a site remote from the previous myocardial infarction was associated with a greater incidence of ventricular fibrillation within 1 h from the onset of ischemia in the pinacidil-treated animals (9/15; 60%) as compared to the control group (1/15; 6.7%; p = 0.007). The 24-h cumulative mortality, likewise, was greater in the pinacidil-treated group [13/15 (87%)] as compared to the vehicle-treated control group 3/15; 20%; p = 0.001. Significant cardiovascular and electrophysiologic effects of pinacidil included an increase in heart rate (124 +/- 6-143 +/- 10 beats/min, p less than 0.05) and reductions in the refractory periods of normal (178 +/- 2-166 +/- 4 ms, p less than 0.05) and peri-infarcted (170 +/- 5-185 +/- 5 ms, p less than 0.01) myocardial regions. It is concluded that pinacidil does not alter the responsiveness of the postinfarcted heart to programmed electrical stimulation. However, in the presence of a superimposed acute ischemic event, pinacidil increases the potential for the development of ventricular fibrillation in a subset of postinfarcted animals that otherwise show a low risk with respect to the development of lethal arrhythmias. It is hypothesized that the increased tendency to develop ventricular fibrillation is associated with the pinacidil-induced reduction in the ventricular refractory period. This conclusion is consistent with the known ability of pinacidil to enhance potassium efflux during myocardial repolarization and to decrease the duration of the action potential.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Chi L,Uprichard AC,Lucchesi BRdoi
10.1097/00005344-199003000-00016subject
Has Abstractpub_date
1990-03-01 00:00:00pages
452-64issue
3eissn
0160-2446issn
1533-4023journal_volume
15pub_type
杂志文章abstract::We recently found that TGF-beta increases ET-1 secretion in MDCK, a renal tubular cell line. The secretion of ET-1, by a confluent monolayer of MDCK cells grown on a filter, to the basolateral side of the epithelium was two times greater than that to the apical side. However, TGF-beta-increased ET-1 and big ET-1 secre...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199100177-00065
更新日期:1991-01-01 00:00:00
abstract::This report summarizes the most important results of 11 studies regarding efficacy and safety of bisoprolol in patients with stable angina pectoris due to coronary heart disease. Assessments carried out 2-3 h after the administration of the beta 1-selective adrenoceptor blocking agent bisoprolol revealed that the dose...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198511001-00029
更新日期:1986-01-01 00:00:00
abstract::In patients routinely treated with metoprolol, influences of CYP2D6 genotype on the response of heart rate to isoproterenol (IP) were studied at its peak and trough concentrations and were compared with those of bisoprolol. In 72 patients treated with metoprolol or bisoprolol, CYP2D6 genotype (ie, CYP2D6*1, *2, *4, *5...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/01.fjc.0000184117.76188.68
更新日期:2005-11-01 00:00:00
abstract::The nitric oxide (NO) synthase activity present in murine J774.2 monocyte/macrophages was characterized in terms of its intracellular localization, substrate specificity, and Ca2+ dependency. Traces of constitutive NO synthase activity were found in the microsomal fraction from noninduced J774.2 cells, whereas no NO s...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199204002-00039
更新日期:1992-01-01 00:00:00
abstract::Experience with angiotensin converting enzyme (ACE) inhibitor drugs as with other antihypertensive agents, is limited in the elderly. Nevertheless, they appear effective and well tolerated but without evidence to suggest that they have any special role in the elderly compared to a younger age group. Most are excreted ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1988-01-01 00:00:00
abstract::The function of presynaptic angiotensin II receptors at postganglionic sympathetic terminal axons under conditions of uninterrupted sympathetic impulse traffic was studied in anesthetized rabbits (alfadolone + alfaxalone). Mean arterial pressure, postganglionic renal sympathetic firing rate, the arterial plasma noradr...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199006000-00015
更新日期:1990-06-01 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::Chronic heart failure (HF) is associated with increased systemic (plasma) and reduced local (myocardial) adenosine levels. The final biological action of adenosine in a particular organ or cell population may depend on the relative degree of expression and signaling efficiency of individual adenosine receptor (AR) sub...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e31821dcc0b
更新日期:2011-08-01 00:00:00
abstract::Three consecutive periods in the natural history of atherosclerosis are amenable to medical treatment. Plaque development is the main target of prevention, which also aims at slowing the progression of already existing plaques. The control of several established risk factors (high blood cholesterol, high blood pressur...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/00005344-199500252-00009
更新日期:1995-01-01 00:00:00
abstract::Dietary omega-3 polyunsaturated fatty acids (PUFAs) are readily incorporated into heart and skeletal muscle membranes where, in the heart, animal studies show they reduce O2 consumption. To test the hypothesis that omega-3 PUFAs alter O2 efficiency in humans, the effects of fish oil (FO) supplementation on O2 consumpt...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1097/FJC.0b013e3181911913
更新日期:2008-12-01 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::Phosphatidylinositol 4,5-bisphosphate hydrolysis at the plasma membrane by phospholipase C is one of the major hormone regulated intracellular signaling systems. The system generates the diffusible second messenger IP3 and the membrane bound messenger diacylglycerol. Spatial regulation of this system has been thought ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/FJC.0000000000000195
更新日期:2015-03-01 00:00:00
abstract::The distribution of 3H-digoxin has been measured in a large number of tissues from the central, autonomic, and peripheral nervous system after the induction of ventricular tachycardia by infusing digoxin into anesthetized dogs. In most parts of the nervous system the tissue digoxin concentration was close to that in t...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198111000-00017
更新日期:1981-11-01 00:00:00
abstract::We investigated the mechanism of the vasodepressor effect of endokinin A/B. An intravenous (IV) bolus of endokinin A/B (0.05-0.3 nmol/kg) dose-dependently decreased mean arterial pressure in thiobutabarbital-anesthetized rats. The magnitude of the response was unaffected by IV pretreatment with NG-nitro-L-arginine met...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/01.fjc.0000175236.41573.2a
更新日期:2005-09-01 00:00:00
abstract::The electrophysiological effects of 0.2 mg/kg of intravenously administered verapamil (mean plasma level, 51.3 ng/ml) were evaluated using intracardiac recordings and electrical stimulation in 10 patients with the concealed or manifest Wolff-Parkinson-White syndrome. Verapamil produced a minimal effect on both the ant...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198101000-00002
更新日期:1981-01-01 00:00:00
abstract::The phosphodiesterase inhibitor UK 61260 exhibits positive inotropic activity in animal studies and is under clinical investigation for treatment of congestive heart failure (CHF). We examined the lusitropic and inotropic responses to UK 61260 in electrically driven (1 Hz, 37 degrees C) human auricular trabeculae (AUT...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199206000-00019
更新日期:1992-06-01 00:00:00
abstract::With chronic angiotensin converting enzyme (ACE) inhibition, blood pressure remains controlled throughout the day despite intermittent recovery of normal function of the renin-angiotensin system. This has been taken as evidence to suggest that the disappearance of angiotensin II (Ang II) from the circulation is not th...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1989-01-01 00:00:00
abstract::To evaluate a possible mechanism for the chronic regulation of MAPK/ERK kinase-1 (MEK-1) and p42 mitogen-activated protein kinase (MAPK) we studied the long-term effects of the G-protein-coupled receptor agonist endothelin-1 (ET-1) and the protein tyrosine kinase-coupled receptor agonist platelet-derived growth factor...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
abstract::Twenty-three patients [mean age 49.7 +/- 5.6 years (WHO II-III)] with severe hypertension and not responding to previous drug treatment were included in the study to evaluate the effect of nitrendipine (NTP) as monotherapy and also in combination with propranolol (PRO). After a control period of 10 days, NTP was start...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198806124-00033
更新日期:1988-01-01 00:00:00
abstract::The present study, undertaken in general practice, was designed to evaluate the effects of age on the pharmacodynamics and pharmacokinetics of a conventional and a slow-release formulation (Securon SR) of verapamil. Two groups of 12 patients with essential hypertension were treated in an open, randomized, crossover st...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00005344-198900134-00017
更新日期:1989-01-01 00:00:00
abstract::To assess dose-related effects of enalapril, we treated eight hospitalized hypertensive patients receiving constant sodium intake with incremental doses of this new angiotensin converting-enzyme blocking drug. After a few days of placebo treatment, enalapril was given in single daily doses, starting with 1.25 mg and i...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198600081-00006
更新日期:1986-01-01 00:00:00
abstract:ABSTRACT:Atrial tachypacing is an accepted model for atrial fibrillation (AF) in large animals and in cellular models. Human induced pluripotent stem cells derived cardiomyocytes (hiPSC-CM) provide a novel, human source to model cardiovascular diseases. Here we investigated whether optogenetic tachypacing of atrial-lik...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000951
更新日期:2020-12-22 00:00:00
abstract::Regeneration of the heart after a stroke would be the best biologic response to restore its function. However, although this phenomenon occurs in primitive organisms, the regenerative potential is lost in mammals. Thus, the search for an appropriate cardiac progenitor with the potential to differentiate into a functio...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/FJC.0b013e3181d8bc6d
更新日期:2010-07-01 00:00:00
abstract::Angiotensin II AT1-receptor blockers (AT1-s) prolong survival in experimental postischemic (coronary artery ligation) heart failure (CHF) in rats. The goal of this study was to investigate whether potential beneficial effects of short- and/or long-term treatment with AT1-s on coronary dynamics, function, and structure...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200009000-00008
更新日期:2000-09-01 00:00:00
abstract::LC3B is a marker of autophagic activity, and growing evidence supports its importance in myocardial hypertrophy. Thus, regulating LC3B expression may provide an important avenue to inhibit autophagy and protect against or inhibit pathological myocardial hypertrophy. To address this question, we investigated the effect...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000306
更新日期:2015-12-01 00:00:00
abstract::Recent evidence has shown that the kidneys produce and secrete a member of the atrial natriuretic peptide family, named urodilatin. This 32-amino acid peptide does not circulate in blood, but is secreted into urine. Urodilatin excretion closely parallels renal sodium excretion under various conditions that influence b...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/00005344-199322002-00028
更新日期:1993-01-01 00:00:00
abstract::In this study, we used the spontaneously beating, isolated rat right atrium as an in vitro model to study arrhythmogenic effects of electrical stimulation. A tetrapolar platinum electrode was used for stimulation and recording of atrial electrical activity at 36.5 degrees C (spontaneous rate, 4.9+/-0.3 Hz). A flutter-...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199910000-00001
更新日期:1999-10-01 00:00:00
abstract::Various in vitro and in vivo techniques were used to evaluate the cardiovascular actions of MDL 19205, a new cardiotonic agent. In the anesthetized dog, intravenous administration of MDL 19205 (0.1-1 mg/kg) produced marked increases in cardiac contractile force which were accompanied by small increases in heart rate a...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1984-01-01 00:00:00
abstract::Disruption of atherosclerotic plaques with associated thrombus is responsible for the majority of the acute coronary syndromes. Plaque instability is related closely to the degree of inflammation. Inflammatory cells within the plaque produce cytokines that inhibit collagen production by vascular smooth muscle cells an...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1998-01-01 00:00:00
abstract::Phosphoinositide (PI) turnover, chronotropic and inotropic responses to alpha 1-adrenoceptor activation, and alpha 1-adrenoceptor density were studied in atria from rats with left ventricular myocardial infarction (LVMI) and noninfarcted rats. LVMI was produced after surgical ligation of the left coronary artery in 8-...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199103000-00017
更新日期:1991-03-01 00:00:00