Heart Failure
Role of oxidative stress in transition of hypertrophy to heart failure.
Dhalla AK; Hill MF; Singal PK
Journal of the American College of Cardiology 1996 Aug;28(2):506-14
OBJECTIVES: In an attempt to define the role of increased oxidative stress
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 in guinea pigs.
BACKGROUND: Hyperfunctional heart hypertrophy has been shown to be accompanied
by an increase in the endogenous antioxidant reserve, whereas congestive
heart failure is accompanied by a decrease in this reserve. The effects
of vitamin E, a naturally occurring antioxidant, on the development of
heart failure from a hypertrophic stage were examined. METHODS: The ascending
aorta in guinea pigs was coarcted. For vitamin treatment, slow-release
pellets were implanted at the time of the operation. The animals were
assessed at 10 and 20 weeks for hemodynamic function, myocardial structure,
antioxidant agents and oxidative stress. RESULTS: Banding of the ascending
aorta in guinea pigs resulted in hyperfunctional hypertrophy at 10 weeks,
which was followed by congestive heart failure at 20 weeks. Hypertrophied
hearts showed decreased oxidative stress, as evidenced by a higher oxidation-reduction
(redox) state and less lipid peroxidation, whereas the failure stage was
characterized by increased oxidative stress. Supplementation of animals
with timed-release vitamin E tablets resulted in an increased myocardial
content of the vitamin, and the banded animals did not develop any signs
of heart failure at 20 weeks. Hemodynamic function at 20 weeks in these
vitamin E-treated animals was also better maintained. The myocardial reduced
glutathione/oxidized glutathione ratio of vitamin E-treated animals at
20 weeks was higher and lipid peroxidation was less compared with the
untreated animals. Ultrastructural abnormalities were significantly less
in the vitamin E-treated hearts compared with the untreated failing hearts
at 20 weeks. CONCLUSIONS: An improved myocardial redox state with vitamin
E therapy, coupled with the modulation of the development of heart failure,
may indicate a pathophysiologic role for increased oxidative stress in
the pathogenesis of heart failure. This study suggests the potential therapeutic
value of long-term antioxidant treatment in modulating or preventing the
pathogenesis of heart failure.
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