Abstract:
OBJECTIVES:Early thrombolysis can reduce infarct size and enhance the long term recovery of contractile function after acute myocardial infarction. These benefits of early reperfusion may be confounded, however, by platelet mediated reocclusion after initial lysis, and "reperfusion injury" mediated by oxygen derived free radicals. Superoxide dismutase (SOD)--as well as its action as a potent free radical scavenging agent--inhibits platelet aggregation in vitro. Thus our primary objectives were to determine whether SOD+catalase, given as adjuvant therapy with recombinant human tissue plasminogen activator, could inhibit platelet aggregation and thereby reduce the time to lysis and maintain arterial patency. Whether SOD+catalase enhanced myocardial salvage or improved acute recovery of contractile function in the setting of thrombosis/thrombolysis was also assessed. METHODS:Two anaesthetised open chest canine models were used: a model of thrombosis/thrombolysis and an in vivo model of platelet aggregation. In protocol I coronary thrombosis was induced by endothelial injury and injection of blood+thrombin+CaCl2. At three hours after occlusion, control animals received saline and tissue plasminogen activator and treated dogs received SOD+catalase and tissue plasminogen activator. Variables measured included coronary blood flow (for assessment of the time to lysis and incidence and duration of spontaneous reocclusion); regional myocardial blood flow; segment shortening; and infarct size. In protocol II dogs underwent endothelial injury and coronary stenosis, resulting in cyclic variations in coronary blood flow caused by formation and dislodgement of platelet thrombi. At 30 minutes after placement of the stenosis, dogs received either saline and tissue plasminogen activator or SOD+catalase and tissue plasminogen activator. Variables measured included the frequency of cyclic flow variations and the duration of occlusion per 30 minute time interval. RESULTS:SOD+catalase slightly reduced the time required to achieve reflow: time to lysis was 35(SEM 5) v 22(4) minutes for control v treated groups (p < 0.05). Protocol II showed that this accelerated time to lysis was due to acute inhibition of platelet aggregation by the scavenging agents. Despite continuous infusion however, SOD+catalase failed to maintain vessel patency in either limb of the study. In protocol I, reocclusion occurred in 90% of control dogs (with 49(8)% of the time after initial lysis spent reoccluded), v 83% in the treated group (36(12)% of the time reoccluded; NS v controls). Also, both groups remained dyskinetic after reflow: at one hour after initial lysis, segment shortening was -6(9)% v -6(20)% of baseline preocclusion values in the subset of control v treated dogs in which the left anterior descending coronary artery was patent at the time of measurement (NS). Finally, infarct size was similar in both groups, averaging 32(9)% v 38(9)% of the myocardium at risk in control v treated animals (NS). CONCLUSIONS:Although SOD+catalase acutely attenuated platelet aggregation and slightly accelerated lysis, these agents failed to limit platelet mediated rethrombosis. Furthermore, SOD+catalase did not enhance myocardial salvage and did not improve acute recovery of contractile function after thrombosis/thrombolysis. Thus SOD+catalase given as adjuvant therapy with tissue plasminogen activator did not have a substantial beneficial effect on either the efficacy of thrombolysis or on "reperfusion injury" in this canine model.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Przyklenk K,Kloner RAdoi
10.1093/cvr/27.6.925subject
Has Abstractpub_date
1993-06-01 00:00:00pages
925-34issue
6eissn
0008-6363issn
1755-3245journal_volume
27pub_type
杂志文章abstract:OBJECTIVE:The K(+) channel encoded by the human ether-a-go-go-related gene (HERG) is crucial for repolarization in the human heart. In order to investigate the impact of HERG current (I(Kr)) on the incidence of cardiac arrhythmias, we generated a transgenic mouse expressing HERG specifically in the heart. METHODS AND ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2004.09.030
更新日期:2005-01-01 00:00:00
abstract:OBJECTIVE:Transiently altering the atrial activation sequence induces atrial memory, manifested as an altered atrial gradient as measured in electrocardiographic XYZ leads. We hypothesized that protracted periods of left atrial impulse initiation alter the atrial gradient in a manner predictive of arrhythmias. METHODS...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(03)00536-4
更新日期:2003-11-01 00:00:00
abstract:OBJECTIVE:Chlamydia pneumoniae infection has been associated with atherosclerosis, although the mechanisms by which C. pneumoniae contribute to atherogenesis remain unclear. Altered production of nitric oxide, a known bactericidal and anti-inflammatory agent, represents one possible mechanistic link. To examine this is...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(03)00389-4
更新日期:2003-10-15 00:00:00
abstract:AIM:To assess whether endothelin-1 (ET-1) induces the in vivo expression of inflammatory-related proteins, namely cyclooxygenase-2 (COX-2) and tissue factor, in the myocardium and circulating leukocytes of guinea-pigs. The involvement of platelets was also analyzed. METHODS:ET-1 (0.013 microg/min) was infused to male ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(02)00657-0
更新日期:2003-01-01 00:00:00
abstract:OBJECTIVE:This study investigated whether endothelial dysfunction occurs in mesenteric arteries of apoE-deficient mice and determined the role of endothelin (ET)-1, which is increased in human atherosclerosis, using an orally active endothelin ET(A) receptor antagonist. METHODS:ApoE-deficient and C57BL/6J control mice...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(01)00469-2
更新日期:2002-02-01 00:00:00
abstract:STUDY OBJECTIVE:The aim was to compare the temporal sequence and structural relationship between perivascular and interstitial fibrosis and microscopic scarring seen in the left ventricle in response to either a transient or sustained stimulus to fibrosis. DESIGN:In 72 male Wistar rats (250-350 g) the transient stimul...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/24.9.741
更新日期:1990-09-01 00:00:00
abstract:OBJECTIVES:Gap junctions have been demonstrated ultrastructurally in cardiac regions where connexin40 (Cx40) and connexin43 (Cx43) protein could not be detected immunohistochemically. We investigated therefore the distribution of their mRNAs with more sensitive techniques. METHODS:In situ hybridizations with Cx40 and ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/0008-6363(96)00131-9
更新日期:1996-11-01 00:00:00
abstract:OBJECTIVE:The highly selective adenosine A1 receptor agonist, 2-chloro-N6-cyclopentyl-adenosine (CCPA), has been shown to be as cardioprotective as ischaemic preconditioning when evaluated with an early staining method using tetrazolium. However, tetrazolium-positive tissue measured 3 h after reperfusion may still over...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.4.652
更新日期:1993-04-01 00:00:00
abstract::Eighty-one consecutive patients representing a wide clinical spectrum were studied to assess the degree of limitation of the atrial extrastimulus technique for measurement of atrioventricular node refractoriness; and, to determine the relationship between conductivity and functional refractoriness of the atrioventricu...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/16.8.457
更新日期:1982-08-01 00:00:00
abstract:OBJECTIVE:Increased expression of the cardiac natriuretic peptides (NP), atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) is observed during chronic hemodynamic overload. The mechanisms underlying this process are not fully understood. In vitro, endothelin 1 (ET-1) is a powerful stimulator of cardiac...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(00)00311-4
更新日期:2001-03-01 00:00:00
abstract:OBJECTIVE:Insulin seems to have vasodilator properties, but it is unclear if insulin in postprandial concentrations is a specific vasodilator of skeletal muscle resistance arterioles only or that various types of vessels are affected. The aim of the present study was to determine the direct effects and the time course ...
journal_title:Cardiovascular research
pub_type: 临床试验,杂志文章
doi:10.1016/s0008-6363(97)00035-7
更新日期:1997-04-01 00:00:00
abstract::STUDY OBJECTIVE - The aim of the study was to determine the changes in the beta adrenergic system induced by cardiac hypertrophy due to valvular aortic stenosis. DESIGN - Density of beta adrenoceptors, cardiac tissue noradrenalime concentrations, coronary blood flow (using radioactive microspheres), and haemodynamic v...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/24.1.65
更新日期:1990-01-01 00:00:00
abstract:OBJECTIVES:Annexin A7 is involved in cardiomyocyte membrane organization and Ca(2+)-dependent signalling processes. We investigated the impact of annexin A7 on cardiac electrophysiological properties using an annexin A7-deficient mouse strain (annexin A7(-/-)). METHODS:Nineteen adult annexin A7(-/-) and 14 wild-type m...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2007.07.001
更新日期:2007-11-01 00:00:00
abstract:OBJECTIVE:The aim was to investigate whether intrinsic cardiac neurones can be involved in the genesis of ventricular arrhythmias. METHODS:Nicotinic, muscarinic, beta adrenergic, peptidergic, and amino acidergic agonists, as well as purinergic compounds, were individually administered in microliter quantities adjacent...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.5.636
更新日期:1994-05-01 00:00:00
abstract:OBJECTIVE:The aim was to examine whether an absolute reduction in energy supply is required for preconditioning against myocardial infarction, and whether an episode of increased adrenergic activity with or without supply-demand imbalance is capable of triggering cardioprotection. METHODS:41 anaesthetised dogs were su...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.11.2071
更新日期:1993-11-01 00:00:00
abstract::Conventional antithrombotic treatments with antiplatelet, anticoagulant or fibrinolytic drugs are not uniformly successful and are associated with hemorrhagic side effects. Thus, new approaches to the prevention and treatment of arterial thrombosis are desirable. The gene transfer approach is particularly attractive b...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(97)00153-3
更新日期:1997-09-01 00:00:00
abstract:AIMS:Atrial fibrillation (AF) is the most common cardiac arrhythmia, and early-onset lone AF has been linked to mutations in genes encoding ion channels. Mutations in the pore forming subunit KV4.3 leading to an increase in the transient outward potassium current (Ito) have previously been associated with the Brugada S...
journal_title:Cardiovascular research
pub_type: 杂志文章,多中心研究
doi:10.1093/cvr/cvt028
更新日期:2013-06-01 00:00:00
abstract:AIMS:Previous studies on the role of stem cell factor (SCF) in endothelial progenitor cell (EPC)-mediated neovascularization have focused on the EPC mobilization and homing process. However, the direct effects of SCF on neovascularization activity of EPCs have not been characterized. We sought to determine whether SCF ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvr161
更新日期:2011-10-01 00:00:00
abstract:OBJECTIVE:The aim was to investigate the effect on the coronary network of the interaction between high arterial blood oxygen tension (PaO2) and stimulation by the alpha adrenergic agonist phenylephrine or by serotonin in an isolated, blood perfused rabbit heart preparation. METHODS:Fresh pig erythrocytes in Krebs-Hen...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.9.1326
更新日期:1994-09-01 00:00:00
abstract:STUDY OBJECTIVE:The aim of the study was to test an intermittent ECG synchronised suction device which was added to a coronary vein retroinfusion system (selective suction and retroinfusion = SSR) in order to transport oxygenated fluid more efficiently into ischaemic myocardium. DESIGN:The suction period preceding the...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/24.6.456
更新日期:1990-06-01 00:00:00
abstract::End-diastolic current thresholds have been measured in 12 open-chested dogs with epicardial disc electrodes ranging in radius from 0.01 to 9.0 mm. The current threshold for cathodal 1 ms impulses proved to be independent of electrode size for radii smaller than 0.2 mm and proportional to the radius to the power 1.5 fo...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/12.8.477
更新日期:1978-08-01 00:00:00
abstract::The last decade has seen a dramatic increase in the understanding of the molecular basis of arrhythmias. Much of this new information has been driven by genetic studies that focused on rare, monogenic arrhythmia syndromes that were accompanied or followed by cellular electrophysiological or biochemical studies. The ma...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2005.04.005
更新日期:2005-08-15 00:00:00
abstract:AIMS:Mast cells participate importantly in abdominal aortic aneurysms (AAAs) by releasing inflammatory cytokines to promote vascular cell protease expression and arterial wall remodelling. Mast cells accumulate in AAA lesions during disease progression, but the exact chemokines by which mast cells migrate to the site o...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvs262
更新日期:2012-12-01 00:00:00
abstract:OBJECTIVE:Important physiological and pathophysiological conditions are associated with changes in secretion and synthesis of atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP). The aim of this study was to examine the effects of mechanical stretch and endothelin-1 on ANF and BNP secretion and gene exp...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.10.1519
更新日期:1994-10-01 00:00:00
abstract::The effects of L-propionylcarnitine on the recovery of cardiac contractile performance after global ischaemia and reperfusion were studied in isolated perfused rat hearts. The addition of either 5.5 or 11 mmol X litre-1 L-propionylcarnitine significantly improved the recovery of cardiac output, left ventricular pressu...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/20.7.536
更新日期:1986-07-01 00:00:00
abstract::Atrial fibrillation (AF) is the most commonly encountered clinical arrhythmia associated with pronounced morbidity, mortality, and socio-economic burden. This pathological entity is associated with an altered expression profile of genes that are important for atrial function. MicroRNAs (miRNAs), a new class of non-cod...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvq350
更新日期:2011-03-01 00:00:00
abstract::A mathematical formulation of the blood flow behaviour through a capillaron model is described. The formulation is applied to the analysis of post-occlusion (reactive) hyperaemia and autoregulation. ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/10.1.13
更新日期:1976-01-01 00:00:00
abstract:OBJECTIVE:3-Methylcholanthrene (MC), a polycylic aromatic hydrocarbon, induces atherogenesis in mice fed an atherogenic diet. In this study, we tested the hypothesis that MC would induce DNA adducts in mouse aortic smooth muscle cells (SMCs) and that cytochrome P4501B1 (CYP1B1) plays an important role in the activation...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(01)00536-3
更新日期:2002-03-01 00:00:00
abstract::Most of our knowledge about the modulation of platelet function by catecholamines is based on observations of acute in vitro actions. Little is known about the effects of chronically elevated or reduced adrenergic stimulation of the platelets. We therefore treated rats for 8 weeks with either adrenaline or the beta-bl...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/23.2.112
更新日期:1989-02-01 00:00:00
abstract::Atrial fibrillation (AF) is the most common tachyarrhythmia in clinical practice. Over decades of research, a vast amount of knowledge has been gathered about the causes and consequences of AF related to cellular electrophysiology and features of the tissue structure that influence the propagation of fibrillation wave...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvw007
更新日期:2016-04-01 00:00:00