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Relative toxicity of cardiotonic agents

Some induced more cardiac and skeletal myocyte apoptosis and necrosis in vivo than others

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Abstract

We sought to determine the relative myotoxicity of a sample of cardiotonic (catecholaminergic and PDE Inhibitory) agents currently available for clinical use. Male Wistar rats (292±24g) were administered single subcutaneous injections of 20 mmol kg−1 of each agent. Myocyte apoptosis (caspase-3 and annexin-V) and necrosis (anti-myosin antibody) were detected immunohisto-chemically on cryosections of the heart and soleus muscle. All of the cardiotonic agents except dopamine produced significant amounts of cardiomyocyte death compared with the vehicle controls, with necrosis (range 2–8%, p<0.01) approximately one order of magnitude greater in extent than apoptosis (range 0.06–0.5%, p<0.05). The incidence of necrosis induced by norepinephrine (8%) was approximately twice that of epinephrine and isoproterenol (4%) and four times that of dobutamine and milrinone (2%). All agents were also toxic to the soleus muscle (range 0.1–8%), but isoproterenol (8%, p<0.05) and epinephrine (4%, p<0.05) were the most significant. No cell death was detected in control animals treated with only the vehicle. Amajority of cardiotonic agents currently in clinical use are toxic to cardiac and skeletal myocytes. These observations suggest that judicious clinical use of such agents requires careful weighing of potential benefits againts the harm via accelerated cumulative loss of myocytes.

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Authors and Affiliations

  1. Research Institute for Sports and Exercise Sciences, Liverpool John Moores University, Webster Street, L3 2ET, Liverpool, England

    Jatin G. Burniston, Georgina M. Ellison & David F. Goldspink

  2. Michael Reese Hospital and Medical Center, Chicago, IL, USA

    William A. Clark

  3. Academic Unit of Molecular Vascular Medicine, University of Leeds, England

    Lip-Bun Tan

Authors
  1. Jatin G. Burniston
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  2. Georgina M. Ellison
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  3. William A. Clark
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  4. David F. Goldspink
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  5. Lip-Bun Tan
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Correspondence to Jatin G. Burniston.

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Burniston, J.G., Ellison, G.M., Clark, W.A. et al. Relative toxicity of cardiotonic agents. Cardiovasc Toxicol 5, 355–364 (2005). https://doi.org/10.1385/CT:5:4:355

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  • DOI: https://doi.org/10.1385/CT:5:4:355

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