Key result
4'-Epi-doxorubicin impairs myocardial contractility less than doxorubicin by preserving calcium turnover.
Why the study?
Doxorubicin and 4'-epi-doxorubicin have different cardiotoxic effects and their impact on calcium turnover in heart muscle was unclear.
The inhibition of fast-exchanging membrane-bound calcium turnover is a likely mechanism underlying early anthracycline-induced cardiotoxicity.
Suggests calcium turnover inhibition as early anthracycline cardiotoxicity mechanism; leaves open translation to human myocardium and clinical practice.
Doxorubicin and 4'-epi-doxorubicin, two anthracycline derivatives with different cardiotoxic effects in experimental models, were found to decrease myocardial contractility in isolated guinea pig atria by significantly modifying calcium turnover. This effect seems to be mainly localized on the fast exchanging membrane-bound calcium, while these drugs do not significantly influence the intracellular stores of calcium. 4'-epi-doxorubicin, which induces a less negative inotropic effect than doxorubicin, produces a smaller inhibition of calcium turnover. This supports the hypothesis that the inhibition of calcium turnover and particularly of the fast exchanging calcium compartment is a general mechanism involved in the early anthracycline-induced cardiotoxicity.
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Villani et al. (1980) studied Early anthracycline-induced cardiotoxicity. Doxorubicin and 4'-epi-doxorubicin was evaluated on Myocardial contractility and calcium turnover. Doxorubicin and 4'-epi-doxorubicin decreased myocardial contractility in isolated guinea pig atria by modifying calcium turnover, with 4'-epi-doxorubicin producing a smaller inhibition.
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