title: Aging increases the cardiotoxicity of daunorubicin and daunorubicinol in the rat.
abstract: 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.
authors.affiliation: Clinical Pharmacology and Gerontology Research Unit, Veterans Affairs Medical Center, Boise, Idaho, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Cusack
authors.forename: P S
authors.initials: PS
authors.lastname: Mushlin
authors.forename: C J
authors.initials: CJ
authors.lastname: Johnson
authors.forename: R E
authors.initials: RE
authors.lastname: Vestal
authors.forename: R D
authors.initials: RD
authors.lastname: Olson
mesh_terms: 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
chemical_list: D000903:Antibiotics, Antineoplastic; C000847:daunorubicinol; D003630:Daunorubicin