Abstract 847: Trans-Resveratrol Protects Against Adriamycin-Induced Cardiomyopathy and Improves Survival
Background: The usefulness of adriamycin (ADR), a potent antitumor agent, can be limited by the development of life-threatening cardiomyopathy and heart failure. Subcellular changes leading to heart failure are suggested to be mediated by drug-induced increases in free radical production and lipid peroxidation. We tested the hypothesis that a synthetic derivative of a potent natural antioxidant present in red wine, trans-resveratrol (TR), protects against ADR-induced cardiac damage.
Methods and Results: ADR (cumulative dose, 15 mg/kg body wt) was administered in 90 rats in six equal intraperitoneal injections over a period of 2 weeks. Two weeks after the end of treatment, cardiomyopathy and congestive heart failure were characterized by ascites, congested liver, increased body weight and depressed cardiac function. Administration of TR (1000 mg/kg body weight/day (R-1000) or 300 mg/kg/day (R-300)) started 2 weeks before and continued for 2 weeks during ADR regimen, improved mean arterial pressure (MAP) (73.2±22.2 in controls (C) to 103.5±21.1 in R-300 and 107.8±20.3 mmHg in R-1000, p<0.01), and rate of LV contraction and relaxation (+dP/dT: from 4193.3±1849.3 in C to 5942.7±1028.8 and 6151.7±820.2 in the R-300 and R-1000 groups;-dP/dT: from 2928.2±1375.6 in C to 4547.3±910.2 and 4616.7±607.3 in the R-300 and R-1000 groups (p<0.001 for all)). Ascites was attenuated in both groups treated with TR and survival significantly increased from 63.3% in controls to 83.3% and 90% in the R-300 and R-1000 groups (p<0.03).
Conclusions: Trans-resveratrol provides protection against ADR-induced cardiomyopathy and prolongs survival.