Experimental Cancer
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Exacerbation of doxorubicin cardiotoxicity by digoxin administration in an experimental rabbit model
William C. Reeves,
James W. Griffith,
Mary Ann Wood,
Lawrence Whitesell,
Corresponding Author
William C. Reeves
Section of Cardiology, School of Medicine, East Carolina University, Greenville, NC 27858-4354
Section of Cardiology, School of Medicine, East Carolina University, Greenville, NC 27858-4354Search for more papers by this authorJames W. Griffith
Department of Comparative Medicine, Pennsylvania State University, Hershey, PA 17033
Search for more papers by this authorMary Ann Wood
Section of Cardiology, Department of Medicine, Pennsylvania State University, Hershey, PA 17033, USA
Search for more papers by this authorLawrence Whitesell
Section of Cardiology, Department of Medicine, Pennsylvania State University, Hershey, PA 17033, USA
Search for more papers by this authorWilliam C. Reeves,
James W. Griffith,
Mary Ann Wood,
Lawrence Whitesell,
Corresponding Author
William C. Reeves
Section of Cardiology, School of Medicine, East Carolina University, Greenville, NC 27858-4354
Section of Cardiology, School of Medicine, East Carolina University, Greenville, NC 27858-4354Search for more papers by this authorJames W. Griffith
Department of Comparative Medicine, Pennsylvania State University, Hershey, PA 17033
Search for more papers by this authorMary Ann Wood
Section of Cardiology, Department of Medicine, Pennsylvania State University, Hershey, PA 17033, USA
Search for more papers by this authorLawrence Whitesell
Section of Cardiology, Department of Medicine, Pennsylvania State University, Hershey, PA 17033, USA
Search for more papers by this authorAbstract
The relationship between digoxin administration and the development of doxorubicin cardiomyopathy was evaluated in a chronic experimental rabbit model. We graded the myocardial pathology by conventional light microscopic histologic techniques. Additionally, myocardial fibrosis was quantified by hydroxyproline determinations and myocardial cellular damage by technetium-99m pyrophosphate uptake. Twenty-four rabbits were studied: 6 control, 6 doxorubicin-treated, and 12 digoxin-doxorubicin-treated. Mortality in the digoxin-doxorubicin group was 50%. All other rabbits lived throughout the entire experiment. The severest grades of histologic lesions were seen only in the digoxin-doxorubicin group. Myocardial hydroxyproline content was greater (p < 0.05) in the digoxin-doxorubicin group than in the doxorubicin or control groups. Myocardial technetium-99m pyro-phosphate content was also significantly greater (p < 0.05) in the digoxin-doxorubicin group than in controls. In conclusion, the pretreatment and continued administration of digoxin, together with doxorubicin, increased the severity of myocardial damage and reduced longevity in this experimental model of doxorubicin cardiotoxicity.
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