Role of oxidative stress in transition of hypertrophy to heart failure
Role of oxidative stress in transition of hypertrophy to heart failure
复制标题
DOI：
10.1016/0735-1097(96)00140-4
复制
发表时间：
1996-08-01
影响因子：
24
通讯作者：
Singal, PK
中科院分区：
文献类型：
--
作者：
Dhalla, AK;Hill, MF;Singal, PK
目标。为了确定氧化应激增加在代偿性肥厚向心力衰竭转变过程中的作用，本研究考察了长期维生素E治疗对豚鼠慢性压力过载后心力衰竭发生的影响。功能亢进的心脏肥大已被证明伴随着内源性抗氧化储备的增加，而充血性心力衰竭则伴随着这种储备的减少。研究了维生素E（一种天然抗氧化剂）对肥厚期心力衰竭发展的影响。豚鼠升主动脉收缩。对于维生素治疗，在手术时植入缓释微丸。在第10周和第20周对大鼠血液动力学功能、心肌结构、抗氧化剂和氧化应激进行评估。豚鼠升主动脉绑扎在10周时导致功能性肥厚，随后在20周时出现充血性心力衰竭。肥厚的心脏表现为氧化应激降低，表现为更高的氧化还原（氧化还原）状态和更少的脂质过氧化，而衰竭阶段的特征是氧化应激增加。给动物补充缓释维生素E片可增加心肌中维生素的含量，在20周时，带状带的动物没有出现任何心力衰竭的迹象。这些维生素e治疗的动物在20周时的血流动力学功能也得到了更好的维持。与未处理的动物相比，维生素e处理的动物在20周时心肌还原性谷胱甘肽/氧化性谷胱甘肽比率较高，脂质过氧化程度较低。20周时，维生素e治疗组的心脏超微结构异常明显少于未治疗组。维生素E治疗改善心肌氧化还原状态，加上对心力衰竭发展的调节，可能表明在心力衰竭发病机制中氧化应激增加的病理生理作用。本研究提示长期抗氧化治疗在调节或预防心力衰竭发病机制方面具有潜在的治疗价值。
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 accompa nied 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.