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myocardial inflammation which was suggested by the presence of lymphocytes and
polymorphonuclear myocardial infiltration, degeneration and atrophy of cardiac
myocytes, focal myocardial necrosis and fibrous pericarditis (Bristow et al. 1978). The
subacute cardiotoxic effects can be distinguished from the chronic cardiotoxic effects by
the presence of this inflammatory response, which is usually absent in the chronic
cardiotoxicity (Bristow et aI. 1978; Ferrans l97B).
[.c.3.Chronic cardiotoxicity (adriamycin-induced cardiomyopathy): One of the most
prominent effects of adriamycin's chronic administration is the development of dosedependent
cardiomyopathy (Buja et al. 1973; Lefrak et al. 1973; Von Hoff et al. 1979).
Lefrak and associates (1973) identified an association between chronic adriamycin
administration and development of drug induced cardiomyopathy and heart failure. It was
also shown that the incidence of adriamycin-induced heart failure rise to the unacceptable
levels when the cumulative doses of the dug exceed 500 mglmz (Von Hoff et al. 1979).
Adriamycin-induced heart failure has been correlated with the patient age, total
adriamycin dose and dose schedule (Von Hoff et al. 1979).The reports on the dose
dependent increase in the incidence of congestive heart failure have resulted in limiting
the cumulative doses of adriamycin below the threshold of 550 múm2 of body surface
area. However, the occulrence of ultrastructural changes in myocardial biopsies and
impaired contractility was documented in patients who have received significantly lower
doses of adriamycin. The occurrence of non-symptomatic ventricular dysfunction in
patients which received sub-threshold doses of adriamycin was also reported (Zambetti et
al. 2001).