Superoxide dismutase activity in Adriamycin-induced cardiotoxicity in humans:: A potential novel tool for risk stratification

Background: Oxidative stress has been implicated in Adriamycin cardiotoxicity experimentally. We evaluated whether changes in systemic markers of antioxidant reserve occur and are associated with left ventricular (LV) dysfunction during Adriamycin use in humans. Methods and Results: We prospectively evaluated oncology patients eligible for Adriamycin chemotherapy. Blood samples for enzymatic (erythrocyte superoxide dismutase activity [SOD-U SOD/mg protein]) and nonenzymatic antioxidants (total radical trapping antioxidant potential [TRAP-U of Trolox/pL plasma]) were collected at baseline (B), intermediate (1), and final (F) cycles. LV ejection fraction (LVEF) was assessed by radionuclide ventriculography. Fifty-one patients (49 +/- 12 years, 90% female) underwent 5.9 +/- 0.9 chemotherapy cycles and received 301 +/- 52 mg/m(2) of Adriamycin. LVEF decreased from 61 +/- 6% (B) to 56 +/- 7% (F) (P <.001), but only 6 (12%) patients developed significant LV systolic dysfunction (LVEF < 50%). SOD activity increased significantly during treatment (4.5 +/- 1.8 [B], 6.0 +/- 2.1 [I], 5.6 +/- 2.2 [F]; P <.01), whereas TRAP values were unchanged. Baseline SOD activity from patients who developed LV systolic dysfunction was significantly higher than from those who maintained normal LVEF (5.9 +/- 1.8 versus 4.3 +/- 1.7; P <.05). In multivariate analysis, baseline SOD levels remained independently associated with LV dysfunction (P =.05). Conclusion: Erythrocyte SOD activity increases after Adriamycin treatment and high baseline levels predicts Adriamycin-induced cardiotoxicity in humans.