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.
Cusack
B J
BJ
Clinical Pharmacology and Gerontology Research Unit, Veterans Affairs Medical Center, Boise, Idaho, USA.
Mushlin
P S
PS
Johnson
C J
CJ
Vestal
R E
RE
Olson
R D
RD
D000375:Aging; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000633:toxicity*; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344
D000903:Antibiotics, Antineoplastic; C000847:daunorubicinol; D003630:Daunorubicin