Linked Life Data

10470987

Source:http://linkedlifedata.com/resource/pubmed/id/10470987

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1999-10-22
pubmed:abstractText
Renin-angiotensin-aldosterone and sympathetic nervous systems overactivity play a major role in worsening the extent of heart failure. Attenuation of neurohumoral activation with angiotensin-converting enzyme (ACE) inhibitors and beta-blockers has proven beneficial in congestive heart failure. Because ACE inhibition is a recommended treatment for heart failure, this study was designed to test the effects on neurohumoral activation, hemodynamics, and left ventricular (LV) volume of the combination of an ACE inhibitor (delapril) with a DA2-dopaminergic receptor/alpha2-adrenoceptor agonist (CHF-1024) or a beta1-adrenoceptor antagonist (metoprolol) after a moderate to large myocardial infarction (MI) in rats. MI was induced by left coronary artery ligation in 134 rats, and six were not operated on. After 2 months, the animals with ECG evidence of MI were treated for 1 more month with CHF- 1024, 0.33 mg/kg/day or with metoprolol (10 mg/kg/day), delivered through implanted osmotic minipumps, in addition to delapril (6 mg/kg/day) in the drinking water. Daily urinary excretion of norepinephrine (NE) and circulating concentration were measured. Hemodynamic variables were measured, and three-dimensional morphometric analysis was done on the diastole-arrested hearts to quantify infarct size and LV geometry. In conscious animals, delapril alone or with CHF-1024 or metropolol did not modify heart rate or systolic blood pressure. Both combination treatments, however, significantly reduced heart rate in anesthetized animals compared with the group receiving vehicle. Infarct size was not different between treatments, averaging 20-22% of LV volume. The threefold increase of LV chamber volume in infarcted rats was significantly attenuated by delapril alone or with CHF-1024 or metoprolol (-37 to -44%, p<0.05). Treatment with a combination of the ACEi and CHF-1024 tended to normalize the shape of the LV cavity. Urinary NE excretion was unaffected by delapril alone but was reduced by the addition of CHF-1024 or metoprolol. In conclusion, 1 month of treatment with doses of delapril having no hemodynamic effect, reduced LV volume in a model of chronic heart failure. When CHF-1024 or metoprolol was given with delapril, sympathetic activation decreased with no unwanted effects, such as excessive hypotension.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0160-2446
pubmed:author
pubmed:issnType
Print
pubmed:volume
34
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
321-6
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:10470987-Adrenergic alpha-Agonists, pubmed-meshheading:10470987-Adrenergic beta-Antagonists, pubmed-meshheading:10470987-Angiotensin-Converting Enzyme Inhibitors, pubmed-meshheading:10470987-Animals, pubmed-meshheading:10470987-Coronary Disease, pubmed-meshheading:10470987-Disease Models, Animal, pubmed-meshheading:10470987-Dopamine Agonists, pubmed-meshheading:10470987-Hemodynamics, pubmed-meshheading:10470987-Male, pubmed-meshheading:10470987-Neurotransmitter Agents, pubmed-meshheading:10470987-Norepinephrine, pubmed-meshheading:10470987-Rats, pubmed-meshheading:10470987-Rats, Sprague-Dawley, pubmed-meshheading:10470987-Receptors, Adrenergic, beta-1, pubmed-meshheading:10470987-Receptors, Dopamine D2, pubmed-meshheading:10470987-Ventricular Dysfunction, Left, pubmed-meshheading:10470987-Ventricular Function, Left
pubmed:year
1999
pubmed:articleTitle
Effects of a DA2/alpha2 agonist and a beta1-blocker in combination with an ACE inhibitor on adrenergic activity and left ventricular remodeling in an experimental model of left ventricular dysfunction after coronary artery occlusion.
pubmed:affiliation
Department of Cardiovascular Research, Instituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't