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Cited by 35Cell death mechanisms and regulationCardiac electrophysiology and arrhythmiasPhosphodiesterase function and regulation

Relative Toxicity of Cardiotonic Agents: Some Induce More Cardiac and Skeletal Myocyte Apoptosis and Necrosis In Vivo Than Others

Burniston, Jatin G., Ellison, Georgina M., Clark, William A., Goldspink, David F., Tan, Lip-Bun·2005·Cardiovascular Toxicology
DOI 10.1385/ct:5:4:355
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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 +/- 24 g) 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 immunohistochemically 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. A majority 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 against the harm via accelerated cumulative loss of myocytes.

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Authors
Burniston, J. G., Ellison, G. M., Clark, W. A., Goldspink, D. F., & Tan, L.-B.
Affiliations
  • Liverpool John Moores University (GB)
  • University of Leeds (GB)
Corresponding author
Burniston, Jatin G.
ORCID
Venue
Cardiovascular Toxicology
Publisher
Springer Science and Business Media LLC
Published
2005
Volume
5
Issue
4
Pages
355-364
ISSN
1530-7905 (ISSN-L)
DOI
10.1385/ct:5:4:355
OpenAlex
W2023582801
Cited by
35
References
37
Citations by year
2026: 2 · 2023: 1 · 2022: 2 · 2017: 3 · 2016: 1 · 2015: 1 · 2014: 5 · 2013: 4 · 2012: 4
FWCI
0.75
Type
journal article
Language
en
Open access
closed
Locations
  • Cardiovascular Toxicology (publishedVersion)
  • PubMed (publishedVersion)
  • Research Portal (King's College London) (submittedVersion)
Funders
  • Fonds National de la Recherche Luxembourg
  • Liverpool John Moores University
  • National Institutes of Health
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Phosphodiesterase function and regulation
Keywords
cardiotonic agents, myotoxicity, cardiomyocyte apoptosis, myocardial necrosis, catecholamines, norepinephrine, epinephrine, isoproterenol, dobutamine, milrinone, dopamine, phosphodiesterase inhibitors, caspase-3, annexin V, soleus muscle
MeSH terms
Animals, Cardiotonic Agents, Disease Models, Animal, Dose-Response Relationship, Drug, Heart, Image Processing, Computer-Assisted, Immunoenzyme Techniques, Injections, Subcutaneous, Isoproterenol, Male, Myocardium, Necrosis, Apoptosis, Muscle, Skeletal, Muscle Fibers, Skeletal, Myocytes, Cardiac, Rats

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