Abstract:
:Apoptosis, a genetically controlled programmed cell death, has been found to play a role in ischemic reperfusion injury in several animal species including rats and rabbits. To examine whether this also is true for other animals, a surgically relevant model was established using an isolated in situ swine heart. Hearts were subjected to 15 min of normothermic regional ischemia by left anterior descending artery (LAD) occlusion followed by 30 min of normothermic cardioplegic arrest and 3 h of reperfusion. Oxygen free radicals have been shown to be the inducers of apoptosis and because reperfusion of ischemic myocardium is associated with the generation of free radicals, an additional group of hearts was preperfused with three different doses (5, 10, and 25 nM) ebselen, a glutathione peroxidase mimic, for 15 min before 15 min of LAD occlusion. Hearts were then subjected to 30 min of normothermic cardioplegic arrest followed by 3 h of reperfusion at normothermia. Control experiments were performed by perfusing the hearts for 4 h at normothermia. Two other groups of hearts were subjected to either 30 or 60 min of LAD occlusion followed by 30 min of cardioplegic arrest without subjecting them to reperfusion. At the end of each experiment, hearts were processed for the evaluation of apoptosis and DNA laddering. The in situ end-labeling (ISEL) technique was used to detect apoptotic cardiomyocyte nuclei while DNA laddering was evaluated by subjecting the DNA obtained from the cardiomyocytes to 1.8% agarose gel electrophoresis followed by photographing under UV illumination. The apoptotic cells appeared only after 90 min of reperfusion, as demonstrated by the intense fluorescence of the immunostained genomic DNA when observed under fluorescence microscopy. None of the ischemic hearts showed any evidence of apoptosis. These results were corroborated with the findings of DNA fragmentation showing increased ladders of DNA bands in the same reperfused hearts. The presence of apoptotic cells and DNA fragmentation in the myocardium was abolished by preperfusing the hearts in the presence of 10 nM ebselen, which also moderated the oxidative stress developed in the heart. Apoptotic cells and DNA ladders were completely absent in the hearts subjected to either 30 or 60 min of LAD occlusion. The results demonstrate that reperfusion of the ischemic heart induces apoptosis, which can be reduced with ebselen by reducing the oxidative stress associated with ischemia/reperfusion.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Maulik N,Yoshida Tdoi
10.1097/00005344-200011000-00009subject
Has Abstractpub_date
2000-11-01 00:00:00pages
601-8issue
5eissn
0160-2446issn
1533-4023journal_volume
36pub_type
杂志文章abstract::Epidemiological studies indicate that there are biological interrelationships between blood pressure and blood lipids that may influence the mechanisms whereby hypertension is associated with an increased risk of coronary artery disease. Serotonin (5-HT) and thromboxane A2, which are released from aggregating platelet...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1992-01-01 00:00:00
abstract::Diabetes and CYP2C19 loss of function (LOF) alleles are associated with the variable antiplatelet activity of the prodrug clopidogrel. We conducted a randomized trial (NCT03613857) to compare the combined and individualized effects of diabetes and CYP2C19 polymorphisms on the antiplatelet reactivity of clopidogrel ver...
journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
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abstract::The purpose of this study was to investigate the mechanisms involved in the angiotensin II-induced increase in the contractile response of the hypertensive wall after prolonged incubation in the organ-bath buffer. In 5-h incubated rings, the contractile response to angiotensin II in aortic rings with endothelium from ...
journal_title:Journal of cardiovascular pharmacology
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doi:10.1097/00005344-199804000-00009
更新日期:1998-04-01 00:00:00
abstract::In a prospective randomized study, we assessed the electrophysiologic effects and the efficacy of ajmaline versus propafenone in patients with accessory pathways (APs). During initiated atrioventricular (AV) reentrant tachycardia or atrial fibrillation (AF), ajmaline (1 mg/kg as bolus followed by infusion of 15 microg...
journal_title:Journal of cardiovascular pharmacology
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更新日期:1994-10-01 00:00:00
abstract::The concentrations of cyclic nucleotides were measured by radioimmunoassay in the plasma of dogs with aconitine-induced atrial fibrillation and of patients with paroxysmal atrial fibrillation. The concentration of cyclic GMP in the plasma of dogs was significantly elevated 30 and 60 min after the onset of atrial fibri...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198111000-00007
更新日期:1981-11-01 00:00:00
abstract::We studied the effects of maprotiline, a tetracyclic antidepressant agent, on transmembrane potentials recorded from papillary muscles of guinea pigs and sinoatrial nodes of rabbits, using standard microelectrode techniques. Maprotiline (10-100 microM) produced dose-dependent decreases in the maximum rate of rise (Vma...
journal_title:Journal of cardiovascular pharmacology
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更新日期:1988-02-01 00:00:00
abstract::Long-term effects of antihypertensive treatment on various electrocardiogram (ECG) voltages and the association between ECG findings at randomization and subsequent mortality were evaluated in the double-blind, placebo-controlled trial of elderly hypertensive patients, conducted by the European Working Party on High B...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00005344-199117002-00020
更新日期:1991-01-01 00:00:00
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199208000-00004
更新日期:1992-08-01 00:00:00
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198810000-00005
更新日期:1988-10-01 00:00:00
abstract::Peripheral vascular resistance, arterial blood pressure, and left ventricular hypertrophy (LVH) are closely related. In systemic hypertension, hemodynamic changes in systolic and diastolic function accompany LVH. Both of these cardiac functions are detected with echocardiography and were measured during this study in ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章
doi:
更新日期:1994-01-01 00:00:00
abstract::The elderly are reported to be less sensitive to the beta-blocking effects of propranolol. However, age-related changes in the stereoselective pharmacokinetics or protein binding of propranolol enantiomers could have confounded the results of previous studies because only 1-propranolol contributes significantly to the...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199011000-00003
更新日期:1990-11-01 00:00:00
abstract::Inhibition of angiotensin-converting enzyme (ACEI) after myocardial infarction reduces remodeling of the surviving myocardium. The cellular signaling mechanisms contributing to remodeling are not fully elucidated. Goal of the current study was to test whether protein kinase C (PKC) is regulated in the surviving myocar...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200305000-00016
更新日期:2003-05-01 00:00:00
abstract::We compared the effect of verapamil slow-release (VSR) and the combination of nifedipine plus propranolol on transient myocardial ischemia in a double-blind study comprising 20 patients with proven coronary artery disease and chronic stable angina. According to the results of 24-h Holter-monitoring recording, patients...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章
doi:10.1097/00005344-199204000-00024
更新日期:1992-04-01 00:00:00
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e31819c74f4
更新日期:2009-03-01 00:00:00
abstract::Rats of the genetically hypertensive (GH) strain do not have an increased body sodium content or increased natriuresis of hypertension. Spontaneously hypertensive rats (SHR), on the other hand, have an increased body sodium content and an increased rate of excretion of a sodium load. They also have an increased appeti...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198400061-00021
更新日期:1984-01-01 00:00:00
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198812006-00016
更新日期:1988-01-01 00:00:00
abstract::The antiarrhythmic agent propafenone and its primary electropharmacologically active metabolite, 5-hydroxypropafenone, are known inhibitors of cardiac myocyte repolarizing currents. We recently documented potent propafenone inhibition of the transient outward potassium current (Ito) in human atrial myocytes from patie...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200109000-00014
更新日期:2001-09-01 00:00:00
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1989-08-01 00:00:00
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journal_title:Journal of cardiovascular pharmacology
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更新日期:2007-04-01 00:00:00
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199322008-00025
更新日期:1993-01-01 00:00:00
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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::Diazepam (DZP) is commonly used in treatment of patients with acute ischemic syndromes to allay anxiety, but benzodiazepines reduce myocardial contractility and increase myocardial blood flow. To investigate the antiischemic effect of DZP, we studied 13 patients with a positive exercise test and angiographically docum...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1994-07-01 00:00:00
abstract::Our previous studies show that activation of the transient receptor potential vanilloid type 1 (TRPV1) channels by a selective agonist, capsaicin (CAP), given unilaterally into the renal pelvis leads to increases in urine flow rate (Uflow) and urinary sodium excretion (UNa) bilaterally, although the mechanisms underly...
journal_title:Journal of cardiovascular pharmacology
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更新日期:2008-05-01 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
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更新日期:2000-11-01 00:00:00
abstract::Conversion of sustained ventricular tachycardia (VT) to nonsustained VT may be a potent mode of antiarrhythmic drug action, whereas a drug's conversion of nonsustained VT to sustained VT could produce serious clinical complications. We tested the effects of two class Ic drugs [encainide (1, 2, and 4 microM) and propaf...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199204000-00004
更新日期:1992-04-01 00:00:00
abstract:OBJECTIVE:We investigate the impact of different regimens of parenteral hydrogen sulfide (H2S) administration on myocardium during ischemia-reperfusion (IR) and the molecular pathways involved in its cytoprotective effects. METHODS:Eighteen male Yorkshire pigs underwent 60 minutes of mid-left anterior descending coron...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e3181b2b72b
更新日期:2009-10-01 00:00:00