Metabolic involvement in adriamycin cardiotoxicity

Abstract

The cardiotoxic effects of adriamycin were studied in mammalian myocardial cells in culture as a model system. Adriamycin inhibited cell growth and the rhythmic contractions characteristic of myocardial cells in culture. A possible involvement of energy metabolism was suggested previously, and in this study the adenylate energy charge and phosphorylcreatine mole fraction were determined in the adriamycin-treated cells. The adenylate energy charge was found to be significantly decreased, while the phophorylcreatine mole fraction was unchanged. Such disparity suggests an inhibition of creatine phosphokinase. The addition of 1 mM adenosine to the myocardial cell cultures markedly increases the ATP concentration through a pathway reportedly leading to a compartmentalized ATP pool. In the adriamycin-treated cells, the addition of adenosine increased the adenylate charge and, concomitant with this inrcease, the cells' functional integrity, in terms of percentage of beating cells and rate of contractions, was maintained.