Basic Research in Cardiology

, 108:384

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
Original Contribution

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.

Keywords

Ischemic cardiomyopathy Beta blockers Regional flow Regional function Cytokines Angiogenesis 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • D. Elizabeth Le
    • 1
    • 6
  • Marco Pascotto
    • 2
  • Howard Leong-Poi
    • 3
    • 7
  • Ibrahim Sari
    • 4
    • 8
  • Antonio Micari
    • 5
    • 9
  • Sanjiv Kaul
    • 6
  1. 1.Hospital and Specialty Medicine - CardiologyPortland VA Medical Center and Knight Cardiovascular InstitutePortlandUSA
  2. 2.Buon Consiglio-Fatebenefratelli HospitalNaplesItaly
  3. 3.Heart and Stroke Foundation of Canada and the Canadian Institutes of Health ResearchOttawaCanada
  4. 4.The Turkish Cardiac SocietyIstanbulTurkey
  5. 5.Italian Society of Cardiology-Aventis FoundationMilanItaly
  6. 6.Knight Cardiovascular InstituteOHSU, UHN62PortlandUSA
  7. 7.St, Michael’s HospitalTorontoCanada
  8. 8.Department of CardiologyGaziantep UniversityGaziantepTurkey
  9. 9.GVM Care and Research Maria Eleonora HospitalPalermoItaly

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