Anti-inflammatory and pro-angiogenic effects of beta blockers in a canine model of chronic ischemic cardiomyopathy: Comparison between carvedilol and metoprolol

D. Elizabeth Le, Marco Pascotto, Howard Leong-Poi, Ibrahim Sari, Antonio Micari, Sanjiv Kaul

    Research output: Contribution to journalArticle

    22 Scopus citations

    Abstract

    There is controversy regarding the superiority of carvedilol (C) over metoprolol (M) in congestive heart failure. We hypothesized that C is superior to M in chronic ischemic cardiomyopathy because of its better anti-inflammatory and pro-angiogenic effects. In order to test our hypothesis we used a chronic canine model of multivessel ischemic cardiomyopathy where myocardial microcatheters were placed from which interstitial fluid was collected over time to measure leukocyte count and cytokine levels. After development of left ventricular dysfunction, the animals were randomized into four groups: sham (n = 7), placebo (n = 8), M (n = 11), and C (n = 10), and followed for 3 months after treatment initiation. Tissue was examined for immunohistochemistry, oxidative stress, and capillary density. At 3 months both rest and stress wall thickening were better in C compared to the other groups. At the end of 3 months of treatment end-systolic wall stress also decreased the most in C. Similarly resting myocardial blood flow (MBF) improved the most in C as did the stress endocardial/epicardial MBF. Myocardial interstitial fluid showed greater attenuation of leukocytosis with C compared to M, which was associated with less fibrosis and oxidative stress. C also had higher IL-10 level and capillary density. In conclusion, in a chronic canine model of multivessel ischemic cardiomyopathy we found 3 months of C treatment resulted in better resting global and regional function as well as better regional function at stress compared to M. These changes were associated with higher myocardial levels of the anti-inflammatory cytokine IL-10 and less myocardial oxidative stress, leukocytosis, and fibrosis. Capillary density and MBF were almost normalized. Thus in the doses used in this study, C appears to be superior to M in a chronic canine model of ischemic cardiomyopathy from beneficial effects on inflammation and angiogenesis. Further studies are required for comparing additional doses of these drugs.

    Original languageEnglish (US)
    Article number384
    JournalBasic Research in Cardiology
    Volume108
    Issue number6
    DOIs
    StatePublished - Nov 1 2013

    Keywords

    • Angiogenesis
    • Beta blockers
    • Cytokines
    • Ischemic cardiomyopathy
    • Regional flow
    • Regional function

    ASJC Scopus subject areas

    • Physiology
    • Cardiology and Cardiovascular Medicine
    • Physiology (medical)

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