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agents (Bristow et al. 1980; Herman et al. 1978). Another characteristic of acute toxicity
is the elevation of CPK activity in the first 48-96 hours after the administration of
adriamycin which could be interpreted as an indication of the development of the early
myocardial damage (Olson and Capen 1977). Morphologic changes are also found to
occur shortly after the administration of adriamycin and are charactenzed by the
fragmentation of nuclear content. The presence of chromatin aggregation in myocytes
was reported in mouse and rat models as early as after a single injection of adriamycin
(Lambertenghi-Deliliers et a|. 1976; Merski et aL 1976). The fact that adriamycin rapidly
penetrates into a nuclei of cardiac myocytes, where it intercalates into DNA causing the
inhibition of DNA polymerases (Wang et al. 1972; Zunino et al. 1975), could explain the
disruption of cardiomyocyte protein production. The damage to cardiac conducting cells
can explain the acute onset of adriamycin-induced arrhythmia's. Adriamycin's acute
toxic effects also include the disruption of cardiac contractility. In vitro studies have
shown that adriamycin exerts dose-dependent, inotropic effects on the heart. In a low
dose, adriamycin is shown to exert a positive inotropic effect (Kim et al. 1980; van
Boxtel et al. 1978; Von Hoff et aL. 1979), however in a larger doses, adriamycin is found
to depress myocardial contractility (Singal and pierce l986).
I.c.2.Subacute cardiotoxicity: The existence of adriamycin-induced, sub-acute
cardiotoxicity was first time acknowledged by Bristow and his colleagues (1978). In this
study authors followed eight patients which developed specific cardiotoxic effects within
the 4 weeks after the treatment with adriamycin. Four of these patients developed
clinical signs of pericarditis, which was associated (in three of them) with serious cardiac
dysfunction(Bristow et al. T978). This dysfunction was caused by the developme¡t of