Publication Detail

The publication detail shows the title, authors (with indicators showing other profiled authors), information on the publishing organization, abstract and a link to the article in PubMed. This abstract is what is used to create the fingerprint of the publication. If any grants are referenced by the publication, they will be listed here as well.

Chronic therapy with metoprolol attenuates cardiomyocyte apoptosis in dogs with heart failure.

H N Sabbah; V G Sharov; R C Gupta; A Todor; V Singh; S Goldstein (Profiled Author: Hani N Sabbah)

Department of Medicine, Henry Ford Heart and Vascular Institute, Detroit, Michigan, USA. HSABBAH1@hfhs.org
Journal of the American College of Cardiology 2000;36(5):1698-705.

OBJECTIVES: The purpose of this study was to determine if therapy with beta-blockade is associated with reduced cardiomyocyte apoptosis. BACKGROUND: Chronic treatment with beta-adrenergic blocking agents has been shown to improve left ventricular (LV) ejection fraction and attenuate progressive LV remodeling in heart failure (HF). Cardiomyocyte apoptosis has also been shown to occur in the failing heart. METHODS: Moderate HF was produced in 14 dogs by intracoronary microembolizations. Dogs were randomized to three months therapy with metoprolol (MET, 25 mg twice daily, n = 7) or to no therapy at all (n = 7). At the end of three months, dogs were sacrificed, and nuclear DNA fragmentation (nDNAf), a marker of apoptosis, was assessed in LV tissue using the TUNEL assay. The number of cardiomyocytes with positive nDNAf labeling per 1,000 was quantified in LV regions bordering old infarcts and in regions remote from infarcts. Endonuclease activity and expression of the antiapoptotic protein Bcl-2 and the proapoptotic proteins Bax and caspase-3 were also evaluated in LV tissue. RESULTS: The number of nDNAf events per 1,000 cardiomyocytes was lower in dogs treated with MET compared with untreated dogs with HF in the border regions (0.35 +/- 0.07 vs. 5.32 +/- 0.77, p < 0.001) as well as the remote regions (0.07 +/- 0.05 vs. 0.39 +/- 0.12, p < 0.05). Endonuclease activity was also significantly lower in MET-treated compared with untreated dogs (25 +/- 3 vs. 37 +/- 2 ng [3H]DNA rendered soluble/min/mg protein). Western blotting for Bcl-2, Bax and caspase-3 showed increased expression of Bcl-2, decreased expression of caspase-3 and no change in Bax in MET-treated compared with untreated dogs. CONCLUSIONS: Chronic therapy with MET attenuates cardiomyocyte apoptosis in dogs with moderate HF. Attenuation of ongoing cardiomyocyte loss through apoptosis may be one mechanism through which beta-blockers elicit their benefits in HF.

1 Originating Grant

• 1.

  Sabbah, Hani N

  PROGRESSION OF HEART FAILURE

  1 April 1994 - 31 December 2003

  NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

  Total Funding: $ 2,329,997

Scientific Context

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