Pichardo J, Palace V, Farahmand F, Singal P K
St. Boniface General Hospital Research Centre and Department of Physiology, University of Manitoba, Winnipeg, Canada.
Mol Cell Biochem. 1999 Jun;196(1-2):51-7.
The suggested role of oxidative stress in the pathogenesis of heart failure is largely based on utilizing left heart failure models. The present study on rats evaluated changes in antioxidants as well as oxidative stress in relation to hemodynamic function subsequent to the right heart failure induced by monocrotaline (50 mg/kg, i.p.). During the post-injection period, monocrotaline (MCT)-treated rats demonstrated a persistent growth depression. Two to three weeks after the injection, MCT-treated rats showed signs of fatigue, peripheral cyanosis and dyspnea. In these rats, right heart hypertrophy was confirmed by a significant increase in right ventricular weight as well as right ventricle to body weight ratio. In MCT-treated rats, there was also a significant increase in right ventricular systolic as well as end diastolic pressures. No change in lung and liver wet/dry weight ratios between MCT-treated and control animals was observed. Based on the hemodynamic data as well as other clinical observations, the functional stage achieved was compensated heart failure. Myocardial antioxidant enzymes, catalase, glutathione peroxidase and superoxide dismutase, in the MCT-treated rats were not different compared to control rats. Vitamin E levels were significantly depressed in the RV and there was no change in retinol levels. There was a significant increase in lipid hydroperoxide concentrations in MCT-treated rats as compared to the control group. These data provide evidence that right heart failure is associated with an increase in oxidative stress.
氧化应激在心力衰竭发病机制中的作用，很大程度上是基于对左心衰竭模型的研究。本研究以大鼠为对象，评估了在腹腔注射50mg/kg野百合碱诱导右心衰竭后，抗氧化剂以及氧化应激与血流动力学功能相关的变化。在注射后的时间段内，接受野百合碱（MCT）处理的大鼠表现出持续的生长抑制。注射后两到三周，MCT处理的大鼠出现疲劳、外周发绀和呼吸困难的症状。在这些大鼠中，右心室重量以及右心室与体重之比显著增加，证实了右心室肥大。在MCT处理的大鼠中，右心室收缩压和舒张末期压力也显著升高。未观察到MCT处理组与对照组动物之间肺和肝湿重/干重比的变化。基于血流动力学数据以及其他临床观察，所达到的功能阶段为代偿性心力衰竭。与对照组大鼠相比，MCT处理的大鼠心肌抗氧化酶（过氧化氢酶、谷胱甘肽过氧化物酶和超氧化物歧化酶）没有差异。右心室中维生素E水平显著降低，视黄醇水平没有变化。与对照组相比，MCT处理的大鼠脂质过氧化氢浓度显著增加。这些数据证明右心衰竭与氧化应激增加有关。
