AGING INCREASES THE CARDIOTOXICITY OF DAUNORUBICIN AND DAUNORUBICINOLIN THE RAT

This study examined effects of aging on the cardiac response in vitro to daunorubicin, a cancer chemotherapeutic agent that causes cardiotox icity. Left ventricular trabeculae carneae from adult (aged 6-9 months ) and old (aged 24-28 months) Fischer 344 rats were placed in oxygenat ed, physiological buffer. preparations were treated with daunorubicin (175 mu M) or saline (controls) over a 210-minute study period. Daunor ubicin-induced decline in contractility (DS and dS/dt) was greater in old compared to adult myocardium (p < .02). Similarly, cardiac relaxat ion (90% relaxation time) was more impaired by daunorubicin in older p reparations (p < 01). Although daunorubicin concentrations were unaffe cted by age, daunorubicinol concentrations in ventricular strips incre ased with time to a greater extent in the older group (p < .05). This study suggests that senescence increases the acute in vitro cardiotoxi city of daunorubicin and that the metabolite, daunorubicinol, may cont ribute to this toxicity.