Heart mitochondria isolated from rabbits subjected to intermittent treatment with adriamycin show a reduced respiratory control, resulting from increase in state 4b oxidation. Continuous daily treatment causes an impairment of respiratory control which is more severe, is due both to increase of state 4b and decrease of state 3 oxygen uptake and occurs after a total amount of drug which does not produce appreciable effects with the intermittent schedule of treatment: however, these changes disappear within 2 weeks from the interruption of the treatment. Mitochondria isolated from adriamycin-treated rabbits show constantly increased permeability to the addition of NADH. On the contrary the ADP/O ratio measured in vitro is essentially unchanged: the same happens with the tissue contents of ATP, ADP, AMP and the metabolites chosen to estimate cytoplasmic and mitochondrial redox states and measured in quick-frozen hearts in vivo. The results are discussed in relation to the possible role of mitochondrial functional defects in the onset of adriamycin cardiomyopathy.
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