Abstract:
:BACKGROUND: Digoxin improves baroreflex function and reduces neurohumoral activation in severe heart failure, but it is uncertain how digoxin affects ventricular remodeling and progression to left ventricular dysfunction. In addition, the effect of digoxin in in vitro beta-adrenoceptor density and function, and contractile reserve in vivo is not well understood. METHODS AND RESULTS: To study this, we compared digoxin with placebo treatment in rats with chronic volume overload induced by aortocaval fistula and in sham-operated control animals. Left ventricular end-diastolic cavity dimensions (LVDd) and wall thickness were measured weekly by in vivo transthoracic echocardiography, and left ventricular mass (LVM) and percent fractional shortening (%FS) were calculated. Six weeks after fistula creation, simultaneous echocardiographic and invasive hemodynamic evaluation at rest and in response to incremental dobutamine (1-10 µg/kg/min intravenously) were measured. Myocardial plasma membrane beta-adrenoceptor density and maximal adenylate cyclase responses (V(max)) to isoproterenol, 5'-guanylylimi dodiphosphate, and forskolin were measured in vitro. Volume overload induced progressive increases in LVDd and LVM over the 6-week study period. Percent fractional shortening at rest, and the change in %FS in response to dobutamine stress were dramatically reduced 6 weeks after fistula creation. Although 6-week fistula animals had unchanged beta-adrenoceptor density (B(max)) and binding affinity (K(d)) as compared with controls, maximal adenylate cyclase responses to stimulation in vitro (V(max)) were markedly reduced. Digoxin treatment prevented this loss of responsiveness of adenylate cyclase but did not affect beta-adrenoceptor density or affinity in vitro. Digoxin had no effect on LVDd, LVM, %FS, or the response to dobutamine infusion in vivo. CONCLUSIONS: Although digoxin prevented beta-adrenoceptor desensitization and improved in vitro myocardial adenylate cyclase response, the cardiac response to adrenergic stimulation in vivo was not significantly improved. These results suggest that the role of beta-adrenoceptor desensitization in the progression from volume overload hypertrophy to left ventricular dysfunction and heart failure may be less important than previously thought. Furthermore, although digoxin treatment did produce modest hemodynamic benefits, it did not prevent progressive remodeling in this model.
journal_name
J Cardiovasc Pharmacol Therjournal_title
Journal of cardiovascular pharmacology and therapeuticsauthors
Sullebarger JT,D'Ambra PM,Clark LC,Thanikarry L,Fontanet HLdoi
10.1177/107424849800300403keywords:
subject
Has Abstractpub_date
1998-10-01 00:00:00pages
281-290issue
4eissn
1074-2484issn
1940-4034pii
S1074248498000327journal_volume
3pub_type
杂志文章abstract:BACKGROUND:Dystrophin-deficient cardiomyopathy is a growing clinical problem without targeted treatments. We investigated whether nicorandil promotes cardioprotection in human dystrophin-deficient induced pluripotent stem cell (iPSC)-derived cardiomyocytes and the muscular dystrophy mdx mouse heart. METHODS AND RESULT...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/1074248416636477
更新日期:2016-11-01 00:00:00
abstract:BACKGROUND:In recent decades, clinical trials have played an increasingly important role in determining how we practice. Trial results proving that a clinical finding poses risk have led to interventions that try to reduce risk. Clinical trials proving that a particular therapy provides better outcome than another ther...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/107424840000500103
更新日期:2000-01-01 00:00:00
abstract::Atrial fibrillation has recently come into clinical and research focus. In particular, ventricular rate control has been carefully compared with atrial rhythm control. Additionally, the recent discovery of atrial stunning has initiated clinical and research interest in atrial remodeling. Atrial fibrillation is more li...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章,评审
doi:10.1177/107424840300800105
更新日期:2003-06-01 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:AIMS:This study aims to evaluate atherosclerosis, oxidative stress, and arterial stiffness attenuation by simvastatin and ivabradine in hyperlipidemic rabbits. METHODS AND RESULTS:Forty rabbits were randomly divided into 4 groups: atherogenic diet (group C), atherogenic diet plus simvastatin (group S), atherogenic die...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/1074248415617289
更新日期:2016-07-01 00:00:00
abstract::We investigated the effect of erythropoietin (EPO) posttreatment on survival time and vascular functions in a mouse model of sepsis. Sepsis was induced by cecal ligation and puncture. After 20 ± 2 hours of sepsis, thoracic aorta was isolated for assessing its reactivity to norepinephrine (NE) and acetylcholine (ACh). ...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/1074248415587968
更新日期:2016-01-01 00:00:00
abstract::BACKGROUND: The effectiveness of antisense oligodeoxynucleotides for in vitro and in vivo studies is limited by a low efficiency of cellular uptake and instability due to degradation by nucleases. To overcome some of these problems, we recently developed a transfer method that utilizes inactivated Sendai virus (hemagg...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/107424849700200308
更新日期:1997-07-01 00:00:00
abstract::Antiplatelet therapy is indicated for the treatment of ischemic stroke or transient ischemic attack (TIA). Aspirin reduces subsequent occlusive vascular events, including recurrent stroke, by about 25%. In such patients, clopidogrel has been evaluated in an effort to further reduce risk. In the Management of Atherothr...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章,评审
doi:10.1177/1074248406296862
更新日期:2006-12-01 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:OBJECTIVE:To investigate the effect of a pharmacist care program on cardiovascular risks in type 2 diabetic patients. METHODS:A 9-month, prospective, randomized, controlled study was conducted in a public hospital in Hong Kong. Patients in the intervention group had regular drug-counseling sessions with pharmacists in...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1177/1074248410396216
更新日期:2012-03-01 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: Nicotine, the active agent in tobacco, is released into the circulation during cigarette smoking. It elevates plasma catecholamines, heart rate, and arterial blood pressure; produces coronary spasm; and increases myocardial work and oxygen demand with concomitant reduction in oxygen supply. This may genera...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/107424849700200407
更新日期:1997-10-01 00:00:00
abstract::Prior studies have suggested that intravenous diltiazem reduces the probability of spontaneous conversion of atrial fibrillation (AF) to sinus rhythm in the electrophysiology laboratory and in patients with postoperative AF. Whether diltiazem exerts the same effect in patients presenting to the emergency department (E...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1177/1074248407303792
更新日期:2007-09-01 00:00:00
abstract:BACKGROUND:CVT-510, N-(3(R)-tetrahydrofuranyl)-6-aminopurine riboside, is a selective A(1)-adenosine receptor agonist with potential potent antiarrhythmic effects in tachycardias involving the atrioventricular (AV) node. This study, the first in humans, was designed to determine the effects of CVT-510 on AV nodal condu...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章,多中心研究
doi:10.1177/107424840100600304
更新日期:2001-07-01 00:00:00
abstract::BACKGROUND: The insulin-resistant (IR) syndrome is causally related to hypertension and cardiovascular events; however, the underlying mechanism remains elusive. The current study was designed to determine (1) whether the IR syndrome causes vascular dysfunction and (2) whether insulin resistance alters the activity of...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/107424849800300205
更新日期:1998-04-01 00:00:00
abstract::The National Heart, Lung, and Blood Institute convened a Workshop on September 20-21, 2010, "New Horizons in Cardioprotection," to identify future research directions for cardioprotection against ischemia and reperfusion injury. Since the early 1970s, there has been evidence that the size of a myocardial infarction co...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type:
doi:10.1177/1074248411402501
更新日期:2011-09-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Myocardial hypertrophy is a common clinical finding leading to heart failure and sudden death. Mitofusin 2 (Mfn2), a hyperplasia suppressor protein, is downregulated in hypertrophic heart. This study examined the role of Mfn2 in myocardial hypertrophy and its potential signal pathway. METHODS...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/1074248410385683
更新日期:2011-06-01 00:00:00
abstract::α-Lipoic acid (LA) has been shown to offer protection against ischemia-reperfusion injury (IRI) in multiple organ systems. N-[(R)-1,2-dithiolane-3-pentanoyl]-L-glutamyl-L-alanine (CMX-2043), a novel analogue of LA, was studied as part of a preclinical development program intended to identify safe and efficacious drug ...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/1074248416640118
更新日期:2016-11-01 00:00:00
abstract:INTRODUCTION:Limited data exist comparing the efficacy and safety of bumetanide- or metolazone-based diuretic regimens to furosemide in acute heart failure (HF). Our purpose was to evaluate the comparative effect on urine output (UO) and renal function between these regimens. METHODS:A retrospective study of hospitali...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/1074248413482755
更新日期:2013-07-01 00:00:00
abstract::Phosphodiesterase inhibitors as inodilators in heart failure are associated with promotion of arrhythmias. Calcium sensitizers have been proposed for the treatment of severe decompensated heart failure. The effect of levosimendan, a calcium sensitizer, and milrinone, a phosphodiesterase inhibitor, on ventricular arrhy...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/1074248406289286
更新日期:2006-06-01 00:00:00
abstract:BACKGROUND:Renalase is a protein that can regulate sympathetic nerve activity by metabolizing catecholamines, while redundant catecholamines are thought to contribute to atherosclerosis (As). Catecholamine release can be facilitated by angiotensin (Ang) II by binding to Ang II type 1 (AT1) receptors. Valsartan, a speci...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/1074248415575967
更新日期:2015-09-01 00:00:00
abstract::Cardio-Oncology has blossomed as a new field in cardiovascular medicine, in large part due to new therapies, which may have cardiovascular sequelae. Despite this, anthracyclines still serve as cornerstone therapy for most pediatric cancers, several solid tumors and hematological malignancies. Cardiotoxicity is the mai...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/1074248420968689
更新日期:2021-03-01 00:00:00
abstract::The peptide hormone relaxin has traditionally been linked to the maternal adaptation of the cardiovascular system during the first trimester of pregnancy. By promoting nitric oxide formation through different molecular signaling events, relaxin has been proposed as a pleiotropic and cardioprotective hormone in the set...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章,评审
doi:10.1177/1074248415617851
更新日期:2016-07-01 00:00:00
abstract::Oxidative stress has been postulated to contribute to the onset and development of heart failure (HF). The efficacy of antioxidant therapy in HF, however, remains controversial. This study evaluates the effect of the antioxidant N-acetylcysteine (NAC, 1 g/kg per day) on cardiovascular function in 2- and 6-month-old Bi...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/1074248410387281
更新日期:2011-06-01 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::Qiliqiangxin (QL), a traditional Chinese medicine, has been shown to be beneficial for chronic heart failure. However, whether QL can also improve endothelial cell function in diabetic rats remains unknown. Here, we investigated the effect of QL treatment on endothelial dysfunction by comparing the effect of QL to tha...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/1074248414537705
更新日期:2015-03-01 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::Dronedarone is a new antiarrhythmic drug for patients with nonpermanent atrial fibrillation (AF). A relatively consistent finding in all trials studying dronedarone was a moderate but significant elevation of serum creatinine. Since dronedarone competes for the same organic cation transporter in the distal renal tubul...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/1074248412453873
更新日期:2013-03-01 00:00:00
abstract::BACKGROUND: Acute myocarditis can progress to chronic heart muscle disease and cardiomyopathy. In the coxsackievirus B(3) (CB(3)) mouse model of myocarditis, early administration of captopril, an angiotensin-converting enzyme (ACE) inhibitor, ameliorated histopathological changes in inflammation, necrosis, and calcifi...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/107424849800300106
更新日期:1998-01-01 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