Attempt to prevent doxorubicin-induced acute human myocardial morphologic damage with acetylcysteine

Doxorubicin induced acute as well as chronic myocardial morphologic alterations. Twenty patients with normal cardiovascular function were randomized to 2 groups based on age and dose of doxorubicin. Group I received placebo 1 hour before doxorubicin administration; group II received acetylcysteine (N-acetyl-L-cysteine) (Nac) 1 hour before doxorubicin. Endomyocardial biopsies were performed at base line at 4 and 24 hours after doxorubicin administration. Biopsy tissue was viewed by electron microscopy, and stereoscopic techniques were used to determine tubular and mitochondrial area. The change of the tubular area was similar in the 2 groups, was maximum at 4 hours, and was proportionately spread throughout the cell. The mitochondrial swelling was also similar in the 2 groups and proportionate throughout the cell but was maximum at 24 hours. This study demonstrated that the acute doxorubicin-induced damage was diffuse and not prevented by Nac.