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Heart Function Challenged with β-Receptor Agonism or Antagonism in a Heart Failure Model

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Abstract

We have shown that chronic treatment with carteolol, a non-selective β-adrenergic receptor antagonist, improved left ventricular (LV) function and survival in an avian model of dilated cardiomyopathy (DCM). The aim of the present study was to compare ex vivo heart function with and without β-agonist and antagonist challenge. We investigated whether intracoronary infusion of a β-blocker, carteolol or β-agonist, isoproterenol decreased contractility. In the DCM group, isoproterenol resulted in a significantly greater increase in heart rate (71% vs. 28% compared to control hearts). To investigate the mechanism for the increase in heart rate, we exposed spontaneously beating neonatal cardiomyocytes to serum immunoglobulin (IgG) isolated from DCM animals. Serum IgG resulted in a significant increase in spontaneous beating rate in neonatal rat cardiomyocytes that was blocked by pre-treatment with a β-blocker. Carteolol challenge did not significantly change heart rate but did significantly increase LV peak pressure in DCM hearts (62%) while coronary artery flow remained unchanged (2.7 ± 0.1 vs 2.7 ± 0.5 ml/min/g). These results show that 1) β-receptor stimulation results in a greater tachycardic response in DCM animals, and 2) carteolo challenge improves myocardial contractility in hearts from DCM animals independent of heart rate or changes in coronary artery flow.

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Authors and Affiliations

  1. Department of Biological Sciences, Tennessee State University, Nashville, TN, 37209

    Benny Washington

  2. Departments of Physiology and Surgery, Morehouse School of Medicine, Atlanta, GA

    Karyn Butler

  3. Boston University School of Medicine and Gwathmey, Inc., Cambridge, MA, 02138

    Angelia A. Doye & Judith K. Gwathmey

  4. Massachusetts General Hospital, Charleston, MA, 02125, USA

    Monica Jang & Roger J. Hajjar

Authors
  1. Benny Washington
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  2. Karyn Butler
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  3. Angelia A. Doye
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  4. Monica Jang
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  5. Roger J. Hajjar
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  6. Judith K. Gwathmey
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Washington, B., Butler, K., Doye, A.A. et al. Heart Function Challenged with β-Receptor Agonism or Antagonism in a Heart Failure Model. Cardiovasc Drugs Ther 15, 479–486 (2001). https://doi.org/10.1023/A:1013755402109

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  • DOI: https://doi.org/10.1023/A:1013755402109

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