Reduction of oxygen uptake in vitro as an index of cardiac toxicity induced by new anthracyclines.

Impairment of respiratory control in myocardial cells has been implicated in attempts to explain the cardiac toxicity of anthracycline antibiotics. This parameter has been found to correlate significantly with depletion of ATP and increase of Ca2+ intracellular concentration in rat heart slices. It has been suggested that 4'-deoxydoxorubicin and 4-demethoxydaunorubicin, whose molecular structures differ slightly from those of doxorubicin and daunorubicin, respectively, might be less cardiotoxic. The present study evaluates the effect in vitro of these new anthracycline derivatives (10 micrograms/ml) on endogenous respiration, measuring oxygen uptake in rat heart slices incubated for 60 min in a Warburg manometric apparatus at 38 degrees C. Mean oxygen uptake values +/- SE (microliter/mg d.w) were as follows: control condition 4.21 +/- 0.2; with doxorubicin 3.03 +/- 0.1; with 4-demethoxydaunorubicin 3.75 +/- 0.1; with 4'-deoxydoxorubicin 3.87 +/- 0.2. Thus, in terms of this parameter, 4'-deoxydoxorubicin and, to a lesser extent, 4-demethoxydaunorubicin are less cardiotoxic than doxorubicin. However, it is well to bear in mind that impairment of respiratory control is only one of the aspects of cellular damage that leads to anthracycline-induced cardiomyopathy.