Abstract:
OBJECTIVE:The aim was to evaluate in a minipig model of acute myocardial infarction the cardioprotection provided by the beta adrenoceptor blocking and vasodilating activities present in carvedilol; comparison was made to the pure beta adrenoceptor antagonist, propranolol. METHODS:Experiments were performed in 25 Yucatan minipigs (9-12 kg), randomly assigned to receive vehicle (n = 7), carvedilol 0.3 mg.kg-1 (n = 6), carvedilol 1 mg.kg-1 (n = 6), or propranolol 1 mg.kg-1 (n = 6). Myocardial infarction was produced by occlusion of the left anterior descending coronary artery for 45 min followed by 4 h of reperfusion. Vehicle, carvedilol (0.3 and 1 mg.kg-1) or propranolol (1 mg.kg-1) were given intravenously 15 min before the coronary artery occlusion. At the end of the reperfusion period, infarct size was determined using Evans blue dye and triphenyltetrazolium chloride staining. Infarct volumes were visualised using computer assisted three dimensional image analysis of the stained myocardial tissue sections. Myeloperoxidase activity was measured in tissue samples removed from normal, infarcted, and at risk areas. RESULTS:Carvedilol (1 mg.kg-1) reduced infarct size by over 90% without producing pronounced changes in systemic haemodynamic variables. The ability of carvedilol to reduce infarct size was clearly dose dependent. Thus infarct size, which represented 27.5(SEM 2.3)% of the area at risk in the vehicle treated group, was only 13.1(4.0)% (p < 0.05) and 2.4(1.5)% (p < 0.01) in pigs treated with carvedilol at 0.3 and 1 mg.kg-1, respectively. In animals treated with propranolol (1 mg.kg-1), infarct size represented 10.9(2.4)% of the area at risk (p < 0.05). The 60% and 91% reductions in infarct size produced by propranolol (1 mg.kg-1) and carvedilol (1 mg.kg-1), respectively, were clearly evident upon three dimensional image analysis. The reduction in infarct size was significantly greater for carvedilol (1 mg.kg-1) compared to propranolol (1 mg.kg-1) at equivalent beta adrenoceptor blocking doses. Pretreatment with propranolol did not reduce the increases in myeloperoxidase activity observed in the area at risk or in the infarcted area. In contrast, carvedilol produced a dose dependent reduction in myeloperoxidase activity in these areas. CONCLUSIONS:Carvedilol limits myocardial necrosis resulting from coronary artery occlusion and reperfusion in a more pronounced manner than the pure beta adrenoceptor antagonist, propranolol. The cardioprotective effect of carvedilol, which reduced infarct size by 91%, may result from the combined effects of beta adrenoceptor blockade and vasodilatation, and possibly also from inhibition of intracellular calcium overload in cardiac cells resulting from antagonism of myocardial alpha 1 adrenoceptors and/or calcium channel blockade. The cardioprotection provided by carvedilol may ultimately be of benefit in hypertensive patients who are at risk for acute myocardial infarction.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Bril A,Slivjak M,DiMartino MJ,Feuerstein GZ,Linee P,Poyser RH,Ruffolo RR Jr,Smith EF 3rddoi
10.1093/cvr/26.5.518subject
Has Abstractpub_date
1992-05-01 00:00:00pages
518-25issue
5eissn
0008-6363issn
1755-3245journal_volume
26pub_type
杂志文章abstract::Acute occlusions of the proximal left circumflex coronary arteriovenous pedicle were performed in open chest anaesthetised dogs. Twenty eight dogs were randomly allocated to receive acebutolol (3 mg X kg-1 twice daily) or placebo given blindly by mouth for five days; a control group of 14 dogs without any pretreatment...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/20.10.721
更新日期:1986-10-01 00:00:00
abstract:AIMS:in this study, we attempted to detect a recent myocardial ischaemic event using ultrasound molecular imaging (UMI) with microbubbles (MB) targeted to intercellular adhesion molecule-1 (ICAM-1) in the late phase of reperfusion. METHODS AND RESULTS:we created a myocardial ischaemia-reperfusion model in 60 C57/BL ma...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvq269
更新日期:2011-01-01 00:00:00
abstract:OBJECTIVE:Our aim was to determine in desmin homozygous mutant mice the viscoelastic properties, the mechanical strength and the structure of the carotid artery. METHODS:To assess the viscoelastic properties of large arteries, we have performed an in vivo analysis of the diameter-, and distensibility-pressure curves o...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(01)00278-4
更新日期:2001-07-01 00:00:00
abstract:OBJECTIVES:We investigated whether Angiotensin II (Ang II) modulates peripheral chemoreflex function through carotid body (CB) chemoreceptors in chronic heart failure (CHF). METHODS:We measured renal sympathetic nerve activity (RSNA) in response to graded hypoxia before and after intravenous administration of Ang II (...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2006.03.017
更新日期:2006-07-01 00:00:00
abstract:OBJECTIVE:Earlier studies have revealed sarcolemmal (SL) defects in congestive heart failure due to myocardial infarction; however, the mechanisms of SL changes in the failing heart are poorly understood. Since congestive heart failure is associated with various metabolic abnormalities including a deficiency of carniti...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00089-9
更新日期:1999-06-01 00:00:00
abstract:Aims:The lectin-like oxLDL receptor-1 (LOX-1) promotes endothelial uptake of oxidized low-density lipoprotein (oxLDL) and plays an important role in atherosclerosis and acute coronary syndromes (ACS). However, its role in arterial thrombus formation remains unknown. We investigated whether LOX-1 plays a role in arteria...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvx015
更新日期:2017-04-01 00:00:00
abstract:STUDY OBJECTIVE:The objectives were (a) to describe the effects of vasoactive drugs in normal rats upon cardiovascular function assessed by computing aortic haemodynamic power and input impedance, each separated into their component parts, and (b) to study the relationship between left ventricular pulsatile power outpu...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/25.11.923
更新日期:1991-11-01 00:00:00
abstract:BACKGROUND:During reperfusion of ischaemic myocardium, Na+/H+ exchange promotes recovery from acidosis resulting in an accumulation of intracellular Na+. This leads to calcium overload via Na+/Ca2+ exchange and might result in cell necrosis contributing to reperfusion injury. METHODS AND RESULTS:We assessed whether HO...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1995-12-01 00:00:00
abstract:AIMS:17β-Oestradiol (E2) and its receptors (ERα and ERβ) are important regulators of physiological and pathological processes in the cardiovascular system. ER act in concert with other regulatory factors mediating oestrogenic effects. However, the underlying mechanisms modulating ER transcriptional activity are not ful...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvs281
更新日期:2012-12-01 00:00:00
abstract:AIMS:Pulmonary arterial endothelial cells (PAECs) express the enzymes needed for generation of l-arginine from intracellular l-citrulline but do not express the enzymes needed for de novo l-citrulline synthesis. Hence, l-citrulline levels in PAECs are dependent on l-citrulline transport. Once generated, l-arginine can ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvs186
更新日期:2012-08-01 00:00:00
abstract::We tested the hypothesis that visualisation of defects on thallium-201 (201Tl) myocardial perfusion images (MPI) depends on the duration of the ischaemic state between 201Tl injection and the time of reperfusion of an occluded coronary artery. Praecordial imaging with a gamma camera was performed in 24 anaesthetised, ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/16.1.47
更新日期:1982-01-01 00:00:00
abstract:OBJECTIVE:Polymorphic ventricular tachycardias (PVT) occur spontaneously in canine hearts under the combination of D-sotalol (S), bradycardia and phenylephrine (PE). We investigated the hypotheses that: (1) the activation patterns of the initial PVT beats would be consistent with an origin in the ventricular conduction...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(98)00036-4
更新日期:1998-06-01 00:00:00
abstract:AIMS:The mesenchymal cushions lining the early embryonic heart undergo complex remodelling to form the membranous ventricular septum as well as the atrioventricular and semilunar valves in later life. Disruption of this process underlies the most common congenital heart defects. Here, we identified a novel role for Sli...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvv040
更新日期:2015-04-01 00:00:00
abstract:OBJECTIVE:Heart failure is associated with reduced function of sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a) but increased function of sarcolemmal Na+/Ca2+ exchanger (NCX), leading to decreased SR Ca2+ content and loss of frequency-potentiation of contractile force. We reported that SERCA2a-overexpression in transg...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2005.05.006
更新日期:2005-09-01 00:00:00
abstract:OBJECTIVES:We measured the uptake of technetium-99m tetrofosmin (99m Tc) and thallium-201 (201 TI) in areas of healed transmural myocardial infarction and in the regions of acute peri-infarction ischemia. METHODS:Anesthetised pigs with a 1-month old transmural infarction elicited by permanent ligature of the left ante...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(97)00316-7
更新日期:1998-04-01 00:00:00
abstract:OBJECTIVE:To examine if adenosine prevents oxidant-induced mitochondrial dysfunction by producing nitric oxide (NO) in cardiomyocytes. METHODS AND RESULTS:Adenosine significantly enhanced the fluorescence of DAF-FM, a dye specific for NO, implying that adenosine induces synthesis of NO. Adenosine-induced NO production...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2004.12.004
更新日期:2005-03-01 00:00:00
abstract:STUDY OBJECTIVE:The aim was to record diastolic transmitral pressure gradients at high sensitivity to quantitate the effect on transmitral pressure gradients of changing the heart rate. DESIGN:Diastolic left atrial and left ventricular pressures were recorded at high sensitivity (40 mm Hg = 10 mm recorded deflection) ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/24.7.560
更新日期:1990-07-01 00:00:00
abstract::Exaggerated cardiovascular responsiveness is common in young men and may cause non-specific symptoms and poor performance. Conventional autonomic function tests are not clinically useful. We have therefore designed a thermal entrainment method to evaluate sympathetic and parasympathetic cardiovascular function in subj...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/23.3.262
更新日期:1989-03-01 00:00:00
abstract:AIMS:Aortic adaptive immunity plays a role in atherosclerosis; however, the precise mechanisms leading to T-cell activation in the arterial wall remain poorly understood. METHODS AND RESULTS:Here, we have identified naïve T cells in the aorta of wild-type and T-cell receptor transgenic mice and we demonstrate that naï...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvz102
更新日期:2020-02-01 00:00:00
abstract::Mechanical stress signals transmitted through the heart walls during hemodynamic loading are sensed by the myocytes, which respond with changes in contractile performance and gene expression. External forces play an important role in physiological heart development and hypertrophy, but disruption of the well-balanced ...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2007.03.029
更新日期:2008-03-01 00:00:00
abstract:AIMS:Tungstate reduces blood pressure in experimental animal models of both hypertension and metabolic syndrome, although the underlying mechanisms are not fully understood. Given that the large-conductance voltage- and Ca(2+)-dependent K(+) (BK) channel is a key element in the control of arterial tone, our aim was to ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvs139
更新日期:2012-07-01 00:00:00
abstract:OBJECTIVE:The mechanosensitive nonselective cation channel (NSC(MS)) and endothelin-1 (ET-1) play critical roles in the regulation of vascular tone. This study was undertaken to investigate the effect of ET-1 on NSC(MS) and on the myogenic response of arteries. METHODS:Cell-attached patch-clamp techniques were applied...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2007.06.021
更新日期:2007-11-01 00:00:00
abstract:OBJECTIVE:The aim was to investigate the ventricular/vascular coupling of the intact right heart under conditions of normal operation and acute pulmonary hypertension. METHODS:Right ventricular contractility was obtained by calculating the end systolic pressure-volume relationship (Ees) and the effective pulmonary art...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/26.9.839
更新日期:1992-09-01 00:00:00
abstract::Sudden cardiac death, which is mainly associated with the presence of life-threatening ventricular arrhythmias, is a common 'killer' among patients with coronary artery disease. Moreover, atrial fibrillation is the most common arrhythmia encountered in the clinical practice. The beneficial effect of statins on cardiov...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2007.02.029
更新日期:2007-07-01 00:00:00
abstract::Although fully explored in larger animals, the role of injection site and sample microsphere content on variability of coronary blood flow (CBF) measurement using the microsphere technique remains controversial in rats despite the fact that this species is extensively used in cardiovascular research. We therefore inve...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/23.5.443
更新日期:1989-05-01 00:00:00
abstract:OBJECTIVE:The aim was to investigate the effect of lowering external potassium on the sensitivity of the normal and hypertrophied rat heart to arrhythmias induced by increases in ventricular wall stress. METHODS:The isolated working heart model was used to compare hypertrophied hearts from the spontaneously hypertensi...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1995-04-01 00:00:00
abstract:OBJECTIVE:Rapid ventricular pacing reliably induces severe congestive heart failure in dogs, with an associated attenuation of baroreflex sensitivity. Unique to this model is the capacity for rapid recovery of haemodynamics and plasma noradrenaline following the cessation of pacing; however, whether baroreflex sensitiv...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.3.384
更新日期:1994-03-01 00:00:00
abstract:OBJECTIVE:The role of phosphorylation of the ryanodine receptor at serine-2808 (RyRS2808) in congestive heart failure (CHF) is controversial, and effects of RyRS2808 phosphorylation on contraction are unclear. It has been reported that diastolic sarcomere length (SL) fluctuations accompany propagating contractile waves...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2005.07.010
更新日期:2006-01-01 00:00:00
abstract:OBJECTIVE:It was our aim to investigate effects of human LDL, copper-, or AAPH-oxidized over different periods of time to different degrees (ox-LDL), on viability and electrophysiological parameters of isolated ventricular myocytes of guinea pigs. METHODS:Guinea pig ventricular myocytes were incubated with ox-LDL or n...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2004.12.009
更新日期:2005-04-01 00:00:00
abstract:AIMS:Intracellular Ca(2+) ([Ca(2+)](i)) regulation in endothelial cells depends on transient receptor potential channels (TRPs), and the role of canonical TRPs (TRPCs) during hypoxia-reoxygenation (H-R) is unclear. We hypothesized that TRPC3 contributes to endothelial nitric oxide (NO) release and that H-R may reduce T...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvr102
更新日期:2011-08-01 00:00:00