Journals of Gerontology Series A: Biological Sciences and Medical Sciences, Vol 51, Issue 5 B376-B384, Copyright © 1996 by The Gerontological Society of America
Aging increases the cardiotoxicity of daunorubicin and daunorubicinol in the rat
BJ Cusack, PS Mushlin, CJ Johnson, RE Vestal and RD Olson
Clinical Pharmacology and Gerontology Research Unit, Veterans Affairs Medical Center, Boise, Idaho, USA.
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.
