Role of oxidative stress in transition of hypertrophy to heart failure.
OBJECTIVE
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.
Dhalla
A K
AK
Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Canada.
Hill
M F
MF
Singal
P K
PK
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D005978:Glutathione / Q000378:metabolism; D006168:Guinea Pigs; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D006439:Hemodynamics / Q000187:drug effects; D017379:Hypertrophy, Left Ventricular / Q000150:complications / Q000378:metabolism*; D015227:Lipid Peroxidation; D008297:Male; D008854:Microscopy, Electron; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D014810:Vitamin E / Q000494:pharmacology* / Q000627:therapeutic use
D000975:Antioxidants; D014810:Vitamin E; D005978:Glutathione