Exacerbation of doxorubicin cardiotoxicity by digoxin administration in an experimental rabbit model

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 less than 0.05) in the digoxin-doxorubicin group than in the doxorubicin or control groups. Myocardial technetium-99m pyrophosphate content was also significantly greater (p less than 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.