ROLE OF OXIDATIVE STRESS IN TRANSITION OF HYPERTROPHY TO HEART-FAILURE

Objectives. In an attempt to define the role of increased oxidative st ress in the transition from compensatory hypertrophy to heart failure, this study examined the effects of long-term vitamin E therapy on the occurrence of heart failure subsequent to chronic pressure overload i n guinea pigs. Background. Hyperfunctional heart hypertrophy has been shown to be accompanied by an increase in the endogenous antioxidant r eserve, whereas congestive heart failure is accompa nied by a decrease in this reserve. The effects of vitamin E, a naturally occurring anti oxidant, on the development of heart failure from a hypertrophic stage were examined. Methods. The ascending aorta in guinea pigs was coarct ed. For vitamin treatment, slow-release pellets were implanted at the time of the operation. The animals were assessed at 10 and 20 weeks fo r hemodynamic function, myocardial structure, antioxidant agents and o xidative stress. Results. Banding of the ascending aorta in guinea pig s resulted in hyperfunctional hypertrophy at 10 weeks, which was follo wed by congestive heart failure at 20 weeks. Hypertrophied hearts show ed decreased oxidative stress, as evidenced by a higher oxidation-redu ction (redox) state and less lipid peroxidation, whereas the failure s tage was characterized by increased oxidative stress. Supplementation of animals with timed-release vitamin E tablets resulted in an increas ed myocardial content of the vitamin, and the banded animals did not d evelop any signs of heart failure at 20 weeks. Hemodynamic function at 20 weeks in these vitamin E-treated animals was also better maintaine d. The myocardial reduced glutathione/oxidized glutathione ratio of vi tamin E-treated animals at 20 weeks was higher and lipid peroxidation was less compared with the untreated animals. Ultrastructural abnormal ities were significantly less in the vitamin E-treated hearts compared with the untreated failing hearts at 20 weeks. Conclusions. An improv ed myocardial redox state with vitamin E therapy, coupled with the mod ulation of the development of heart failure, may indicate a pathophysi ologic role for increased oxidative stress in the pathogenesis of hear t failure. This study suggests the potential therapeutic value of long -term antioxidant treatment in modulating or preventing the pathogenes is of heart failure.