Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-4-18
pubmed:abstractText
The benefit of the beta(2)-adrenergic agonist, clenbuterol, in left ventricular assist device patients with dilated cardiomyopathy has been reported, but its effect on ischemic heart failure (HF) is unknown. We investigated whether clenbuterol improves left ventricular remodeling, myocardial apoptosis and has synergy with a beta(1) antagonist, metoprolol, in a model of ischemic HF. Rats were randomized to: 1) HF only; 2) HF + clenbuterol; 3) HF + metoprolol; 4) HF + clenbuterol + metoprolol; and 5) rats with sham surgery. HF was induced by left anterior descending artery (LAD) artery ligation and confirmed by decreased left ventricular fractional shortening, decreased maximum left ventricular dP/dt (dP/dt(max)), and elevated left ventricular end-diastolic pressure (LVEDP) compared with sham rats (p < 0.01). After 9 weeks of oral therapy, echocardiographic, hemodynamic, and ex vivo end-diastolic pressure-volume relationship (EDPVR) measurements were obtained. Immunohistochemistry was performed for myocardial apoptosis and DNA damage markers. Levels of calcium-handling proteins were assessed by Western blot analysis. Clenbuterol-treated HF rats had increased weight gain and heart weights versus HF rats (p < 0.05). EDPVR curves revealed a leftward shift in clenbuterol rats versus metoprolol and HF rats (p < 0.05). The metoprolol-treated group had a lower LVEDP and higher dP/dt(max) versus the HF group (p < 0.05). Clenbuterol and metoprolol groups had decreased myocardial apoptosis and DNA damage markers and increased DNA repair markers versus HF rats (all p < 0.01). Protein levels of the ryanodine receptor and sarcoplasmic reticulum calcium-ATPase were improved in clenbuterol-, metoprolol-, and clenbuterol+metoprolol-treated groups versus HF rats. However, as a combination therapy, there were no synergistic effects of clenbuterol+metoprolol treatment. We conclude that clenbuterol ameliorates EDPVR, apoptosis, and calcium homeostasis but does not have synergy with metoprolol in our model of ischemic HF.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
317
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
553-61
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:16421285-Adrenergic beta-Agonists, pubmed-meshheading:16421285-Adrenergic beta-Antagonists, pubmed-meshheading:16421285-Animals, pubmed-meshheading:16421285-Apoptosis, pubmed-meshheading:16421285-Body Weight, pubmed-meshheading:16421285-Calcium, pubmed-meshheading:16421285-DNA Damage, pubmed-meshheading:16421285-DNA Repair, pubmed-meshheading:16421285-Disease Models, Animal, pubmed-meshheading:16421285-Echocardiography, pubmed-meshheading:16421285-Hemodynamics, pubmed-meshheading:16421285-Homeostasis, pubmed-meshheading:16421285-Myocardial Ischemia, pubmed-meshheading:16421285-Organ Size, pubmed-meshheading:16421285-Rats, pubmed-meshheading:16421285-Rats, Sprague-Dawley, pubmed-meshheading:16421285-Receptors, Adrenergic, beta, pubmed-meshheading:16421285-Ventricular Remodeling
pubmed:year
2006
pubmed:articleTitle
beta(2)-Adrenergic stimulation attenuates left ventricular remodeling, decreases apoptosis, and improves calcium homeostasis in a rodent model of ischemic cardiomyopathy.
pubmed:affiliation
Department of Surgery, Columbia University College of Physicians and Surgeons, New York, New York, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't