PATHIGENESIS OF Anthracycline

Pathogenesis of anthracycline induced cardiotoxicity remain controversial and poorly

understood. Typical pathologic changes in the heart include vacuolar degeneration of the
sarcoplasmic reticulum, swelling and disruption of the mitochondria, and myofilament
degeneration. There is also evidence of myocyte loss. Pathologic evidence includes early studies
showing chromatin condensation, as can be seen in apoptotic cells in the myocardium of
anthracycline-treated patients. Animal studies have shown similar findings. In addition, cell
death likely occurs by necrosis. Elevation of serum troponin is observed in patients treated with
anthracyclines, consistent with the induction of cell death. Endothelial cells and progenitor cell
populations in the heart are also susceptible to anthracycline-induced cell death. Thus one
explanation for anthracycline induced cardiotoxicity is that myocytes are lost with every
exposure and the pool of endogenous reparative cells diminishes, predisposing the heart to
inadequate healing.