Cardiotoxicity of anthracyclines.
This study describes the effects of some anthracyclines (adriamycin, 4-epiadriamycin and esorubicin) on isolated, electrically driven left guinea pig atrium in normodynamic or hypodynamic (Tyrode solution with 0.1 g/1 CaCl2) conditions. Exposure for 60' to the anthracyclines caused a depression of contractile force and of maximal rate of tension development (df/dt). The statistical analysis of data showed an equivalent inhibitory effect between adriamycin and esorubicin, whereas 4-epiadriamycin has in normodynamic conditions greater negative inotropic effects significantly different from that of the two other drugs. Thus the lower toxicity of 4-epiadriamycin observed in vivo by other authors may probably be imputed to a lower concentration of the drug in the heart. The cardiac depressant effects induced by anthracyclines in vitro, as previously reported, are antagonized by new cardiotonic agents whose mechanism of action can be related to an increase in calcium activity in myocardial tissue.
Dipartimento di Farmacologia dell' Università, Milano, Italy.
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R
Bossa
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G
Efstathiu
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I
Galatulas
M A
MA
Nilnci
D000818:Animals; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000633:toxicity*; D004594:Electrophysiology; D015251:Epirubicin / Q000633:toxicity*; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects* / Q000503:physiopathology; D006331:Heart Diseases / Q000139:chemically induced
D015251:Epirubicin; D004317:Doxorubicin; C030851:esorubicin