Role of the fast-exchanging calcium compartment in the early cardiotoxicity of anthracycline analogs.
Two new anthracycline analogs, 4'-epi-doxorubicin and 4'-deoxydoxorubicin, were tested for their cardiotoxicity and their activity on calcium turnover in guinea pig heart. The df/dt was used as an index of contractile force; calcium turnover was studied by means of a radioisotopic technique. 4'-Epi-doxorubicin was found less cardiotoxic than doxorubicin, whereas 4'-deoxydoxorubicin was found almost completely devoid of cardiotoxicity. The different cardiotoxic activity was found to be linearly correlated with the relative capacity to inhibit the fast-exchanging calcium compartment in cardiac muscle: doxorubicin greater than 4'-epi-doxorubicin greater than 4'-deoxydoxorubicin. This result supports that the inhibition of calcium exchange is involved in development of the early cardiotoxicity of anthracyclines.
D000818:Animals; D000970:Antineoplastic Agents; D002118:Calcium / Q000378:metabolism*; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015251:Epirubicin; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism
D000970:Antineoplastic Agents; D015251:Epirubicin; D004317:Doxorubicin; C030851:esorubicin; D002118:Calcium