Aging Increases the Cardiotoxicity of Daunorubicin and Daunorubicinol in the Rat

This study examined effects of aging on the cardiac response in vitro to daunorubicin, a cancer chemotherapeutic agent that causes cardiotoxicity. Left ventricular trabeculae carneae from adult (aged 6-9 months) and old (aged 24-28 months) Fischer 344 rats were placed in oxygenated, physiological buffer. Preparations were treated with daunorubicin (175 microM) or saline (controls) over a 210-minute study period. Daunorubicin-induced decline in contractility (DS and dS/dt) was greater in old compared to adult myocardium (p < .02). Similarly, cardiac relaxation (90% relaxation time) was more impaired by daunorubicin in older preparations (p < 01). Although daunorubicin concentrations were unaffected by age, daunorubicinol concentrations in ventricular strips increased with time to a greater extent in the older group (p < .05). This study suggests that senescence increases the acute in vitro cardiotoxicity of daunorubicin and that the metabolite, daunorubicinol, may contribute to this toxicity.