Abstract:
:The pyrimidine base, orotic acid (OA), markedly improves the function of recently infarcted hearts subjected to global ischemia. The mechanism of cardiac action of OA is unclear, but it has been proposed that OA acts by correcting a relative deficiency of nucleotide precursors required for RNA synthesis in the stressed myocardium or by improving myocardial energy supply. The aim of this study was to investigate the mechanism of action of OA by (1) determining whether a high dose of OA can raise the concentration of pyrimidine metabolites in plasma, liver, and heart; (2) examining the effects of OA on adenine nucleotide (AN) concentrations in normal and infarcted hearts, before and after global ischemia; and (3) determining the effect of uridine, an important metabolite of OA, on myocardial energy metabolism. Three studies were performed: (1) The time course of changes in tissue and plasma concentrations of pyrimidine compounds was examined in unoperated rats after the administration of 100 mg/kg OA. (2) Rats were given OA (30 mg/kg/d) for 2 days after experimental infarction, and tissue and plasma pyrimidine concentrations were examined; the hearts were removed for perfusion in the isolated working rat heart model (37 degrees C), subjected to 30 minutes of global ischemia, and recovery of function was assessed. AN content was assessed in the noninfarcted myocardium before and after ischemia. Isolated hearts were subjected to 30 minutes of hypoxic perfusion and the effect of adding 17 microM uridine to the perfusate was examined. Study 1 showed that OA administration produced an increase in hepatic uridine and cytidine, followed by increased plasma uridine and cytidine (cytidine, +55%, P < 0.001; uridine, +124%, P = 0.011). Myocardial uracil nucleotides increased temporarily after 4 hours (+21%, P < 0.01). In infarcted hearts after 2 days of OA administration, there were no significant changes in myocardial uracil or cytosine nucleotides or total RNA. Infarction significantly reduced functional recovery after global ischemia (sham = 62%; infarct = 26% of preischemic level; P < 0.05). OA improved the recovery of preischemic function by 133% (P < 0.05) in infarcted, but not sham-operated, hearts. Preischemic ATP and total adenine nucleotides (TAN) were decreased in the surviving myocardium of infarcted hearts (ATP reduced from 21.7 +/- 0.8 to 14.7 +/- 0.7 mumol/g dry wt, P < 0.001; TAN decreased from 30.3 +/- 0.8 to 22.4 +/- 1.1 mumol/g dry wt, P < 0.001). OA treatment prevented these reductions. Study 3 showed that uridine improved myocardial ATP and TAN levels, and decreased purine loss in hypoxic hearts. The increased AN levels were accompanied by evidence of enhancement of anerobic glycolysis. We conclude: (1) That OA acts on the heart via the liver by increasing the availability of plasma uridine and cytidine. (2) Uridine is capable of increasing myocardial ATP production by stimulating anerobic glycolysis. (3) OA treatment improves tolerance to global ischemia in infarcted but not normal hearts by preventing depletion of AN in the surviving myocardium.
journal_name
Cardiovasc Drugs Therjournal_title
Cardiovascular drugs and therapyauthors
Rosenfeldt FL,Richards SM,Lin Z,Pepe S,Conyers RAdoi
10.1023/a:1007700716866subject
Has Abstractpub_date
1998-09-01 00:00:00pages
159-70eissn
0920-3206issn
1573-7241journal_volume
12 Suppl 2pub_type
杂志文章abstract:PURPOSE:To assess whether glycoprotein IIb/IIIa inhibition using tirofiban in low risk patients undergoing percutaneous coronary intervention (PCI) may reduce the risk of periprocedural myocardial infarction compared to standard care in poor responders to aspirin and/or clopidogrel. METHODS:We will enroll patients at ...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1007/s10557-008-6121-z
更新日期:2008-08-01 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::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::The efficacy of a fixed combination of 10 mg nifedipine and 100 mg acebutolol was tested in 21 patients with angiographically proven coronary artery disease (CAD). Ejection fraction (EF), emptying and filling rate (VS and VD), and end-systolic volume (ESV) were assessed by means of radionuclide ventriculography at res...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/BF00148473
更新日期:1989-06-01 00:00:00
abstract::With the increased use of long-acting nitroglycerin preparations, there has been greater recognition of the problem of nitrate tolerance. In recent years extensive research has broadened our understanding of the mechanisms of nitroglycerin action and the mechanisms of drug attenuation. This paper reviews the current s...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF01857640
更新日期:1990-02-01 00:00:00
abstract::The novel insights provided by the molecular genetic applied to the study of cardiac arrhythmias have just started to scratch the surface of the complex relationships between the genetic abnormalities of ion channel structure and the susceptibility to life threatening ventricular arrhythmias. These crucial pieces of i...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1023/a:1015793113771
更新日期:2002-03-01 00:00:00
abstract:OBJECTIVE:This review aims at updating the results of cardiac resynchronization therapy (CRT) in mild heart failure patients, and investigating whether CRT can prevent or reverse heart failure progression in an earlier stage. METHODS:Randomized controlled trials of CRT in patients with New York Heart Association (NYHA...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s10557-011-6313-9
更新日期:2011-08-01 00:00:00
abstract::Glucose-insulin-therapy for acute myocardial infarction (AMI) has had a long history, going back 37 years to the pioneering concepts of Sodi-Pallares. Although a recent meta-analysis of a number of smaller trials has suggested mortality benefit, it is only the South American trial, published in Circulation in 1998, th...
journal_title:Cardiovascular drugs and therapy
pub_type: 评论,社论,评审
doi:10.1023/a:1007757407246
更新日期:1999-05-01 00:00:00
abstract::This study was designed to compare once-daily administration of 5-10 mg amlodipine with two daily doses of 40 mg sustained-release isosorbide dinitrate in 59 patients with stable angina using a randomized, double-blind, crossover study design. Anginal episodes, nitroglycerin consumption, and possible adverse events we...
journal_title:Cardiovascular drugs and therapy
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1023/a:1007726722284
更新日期:1997-11-01 00:00:00
abstract::To characterize the effects of OPC-8212, a quinolone inotropic agent, in patients with heart failure, we utilized invasive hemodynamics, exercise testing, 24-hour ambulatory electrocardiograms, and two patient self-assessment questionnaires, before and after 1 month of treatment with OPC-8212, in 17 patients with mode...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/BF00054205
更新日期:1988-12-01 00:00:00
abstract::The purpose of the study was to determine whether a new KATP channel opener, Y 26763 (Y), can influence the electrophysiological properties in the ischemic myocardium as well as to determine whether the blunting effect of the alpha 1-adrenoceptor antagonist bunazosin (BN) on an ischemia-induced shortening of repolariz...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1023/a:1007830607733
更新日期:2000-06-01 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::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::An 82-year old man was admitted with acute pulmonary edema. Myocardial ischemia and electrolyte abnormalities were excluded and he responded promptly to frusemide, nitrates and morphine. On admission, the duration of the QRS interval was markedly abnormal at 240 ms with a nonspecific intraventricular conduction defect...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1023/a:1027384731525
更新日期:2003-07-01 00:00:00
abstract:PURPOSE:The need for novel approaches to cardiovascular drug development served as the impetus to convene an open meeting of experts from the pharmaceutical industry and academia to assess the challenges and develop solutions for drug discovery in cardiovascular disease. METHODS:The Novel Cardiovascular Therapeutics S...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/s10557-017-6739-9
更新日期:2017-08-01 00:00:00
abstract:PURPOSE:In addition to lowering hemoglobin A1C, colesevelam has been shown to improve the atherogenic lipoprotein profile of subjects with type 2 diabetes mellitus (T2DM) when used in combination with metformin and/or sulfonylureas. A recent study evaluated the effects of colesevelam as antidiabetes monotherapy in adul...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1007/s10557-014-6516-y
更新日期:2014-06-01 00:00:00
abstract::Angiotensin-converting enzyme (ACE) inhibitor therapy has been associated with a substantial (> or = 20%) reduction in the risk of major ischemic events in two recent clinical trials with long-term follow-up: Studies of Left Ventricular Dysfunction (SOLVD) and the Survival and Ventricular Enlargement (SAVE) study. Par...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF00877749
更新日期:1995-02-01 00:00:00
abstract:BACKGROUND:Markers of thrombosis, inflammation, endothelial dysfunction and neurohumoral activation such as fibrinogen, D-dimer, C-reactive protein, von Willebrand factor, tumour necrosis factor-alpha and chromogranin-A are reported to be linked to the increase of cardiovascular risk for atherosclerosis progression and...
journal_title:Cardiovascular drugs and therapy
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1023/a:1024394610648
更新日期:2003-01-01 00:00:00
abstract::The following discourse addresses the pharmacologic profile of KT-362, its clinical potential as an anti-arrhythmic agent with associated hypotensive effects, as well as its additional related potential in myocardial ischemia and related sequellae, and the specific cellular actions that may be responsible for these po...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF02018262
更新日期:1990-10-01 00:00:00
abstract:PURPOSE:To assess the effects of electro-acupuncture (EA) on glycemic control, myocardial inflammation, and the progression of diabetic cardiomyopathy in mice with type 2 diabetes. METHODS:Db/Db mice received EA at PC6+ST36 (DM-Acu), non-acupoint simulation (DM-Sham), or no treatment (DM). EA was applied for 30 min pe...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-020-07043-4
更新日期:2020-12-01 00:00:00
abstract:PURPOSE:The glucagon-like peptide-1 (GLP-1) has been shown to exert cardioprotective effects in animals and patients. This study tests the hypothesis that preservation of GLP-1 by the GLP-1 receptor agonist liraglutide or the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin is associated with a reduction of angiote...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-015-6592-7
更新日期:2015-06-01 00:00:00
abstract::People who consume a diet rich in fruit and vegetables have lower risks of cancer, cardiovascular disease and all-cause mortality. Many prospective cohort studies have reported inverse associations between dietary intake or blood levels of beta-carotene and risks of cancer. Several large-scale trials were set up to as...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1023/a:1022134418372
更新日期:2002-09-01 00:00:00
abstract:PURPOSE:Homocysteine (Hcy) is an independent risk factor for cardiovascular diseases that impairs endothelial function. We investigated whether the impaired endothelial function can be restored by the eNOS transcription enhancer AVE3085 in porcine coronary arteries. The effects of AVE3085 against Hcy on eNOS-NO functio...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-013-6478-5
更新日期:2013-12-01 00:00:00
abstract::The time course of myocardial ischemia was studied in canine myocardium by electron microscopy. Ischemia of the myocardium produces ultrastructural alterations of mitochondria, nuclei, contractile apparatus, and the SR- and T-tubular system that are accompanied by loss of glycogen and intracellular edema. These change...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF00054248
更新日期:1988-05-01 00:00:00
abstract::The modifying effect on exercise performance and neuroendocrine response of the nonselective beta blocker timolol (10 mg b.i.d. for 5 days) and the beta 1-selective beta blocker metoprolol (100 mg b.i.d. for 5 days) was studied. The hormones studied were growth hormone, prolactin, cortisol, renin, epinephrine, dopamin...
journal_title:Cardiovascular drugs and therapy
pub_type: 临床试验,杂志文章
doi:10.1007/BF01881530
更新日期:1989-03-01 00:00:00
abstract::High-density lipoprotein cholesterol (HDL-c) has long been referred to as 'good cholesterol' due to its apparent inverse relationship with future CVD risk. More recent research has questioned a causal role for HDL-c in this relationship, however, as both genetic studies and numerous large-scale randomised controlled t...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/s10557-018-06846-w
更新日期:2019-04-01 00:00:00
abstract::Patients with mild to moderate hypertension (diastolic blood pressure > or = 95 and < or = 115 mmHg) and renal dysfunction entered one of two studies to assess the safety of efficacious daily doses of quinapril on renal function and blood pressure. Twenty-four patients with moderate renal impairment (MRI) (creatinine ...
journal_title:Cardiovascular drugs and therapy
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1007/BF00877336
更新日期:1994-04-01 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::Reducing elevated levels of low-density-lipoprotein cholesterol (LDL-C) significantly reduces the incidence of coronary heart disease (CHD) events and mortality in hypercholesterolemic patients. CHD risk reduction is proportional to LDL-C reduction. Despite this knowledge, many physicians are not applying existing tre...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1023/a:1013341606476
更新日期:2001-09-01 00:00:00
abstract::Excess activity of the sympathetic nervous system (SNS) is linked to human obese hypertension and to salt-sensitive hypertension. Paradoxically, reduced SNS activity has been implicated as a contributor to obesity, particularly in animal models, and salt loading usually inhibits SNS activity. We have investigated the ...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/BF00120497
更新日期:1996-06-01 00:00:00