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: B J Cusack, P S Mushlin, C J Johnson, R E Vestal, R D Olson
• Journal: The journals of gerontology. Series A, Biological sciences and medical sciences (J Gerontol A Biol Sci Med Sci) Vol. 51 Issue 5 Pg. B376-84 (Sep 1996) ISSN: 1079-5006 [Print] United States
• PMID: 8808986 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antibiotics, Antineoplastic
• daunorubicinol
• Daunorubicin

Topics

• Aging
• Animals
• Antibiotics, Antineoplastic (toxicity)
• Daunorubicin (analogs & derivatives, toxicity)
• Heart (drug effects)
• In Vitro Techniques
• Male
• Myocardial Contraction (drug effects)
• Rats
• Rats, Inbred F344