Possible Involvement of Mitochondrial Energy-Producing Ability in the Development of Right Ventricular Failure in Monocrotaline-Induced Pulmonary Hypertensive Rats
Possible Involvement of Mitochondrial Energy-Producing Ability in the Development of Right Ventricular Failure in Monocrotaline-Induced Pulmonary Hypertensive Rats
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DOI：
10.1254/jphs.08322fp
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发表时间：
2009-09-01
影响因子：
3.5
通讯作者：
Tanonaka, Kouichi
中科院分区：
文献类型：
--
作者：
Daicho, Takuya;Yagi, Tatsuya;Tanonaka, Kouichi
本研究旨在探讨线粒体能量产生能力的改变在给药大鼠右心衰发展中的可能参与。皮下注射60 mg/kg的大鼠在第6周出现明显的心肌肥大和纤维化，即严重的心脏重构。通过插管和超声心动图方法对大鼠给药后心脏血流动力学的时程研究显示，大鼠心脏双产物降低，心输出量指数降低，右心室Tei指数升高，提示给药后第6周大鼠发生右心衰竭。给药动物右心室肌线粒体耗氧率降低，这与心肌高能磷酸盐的减少有关。此外，给药大鼠线粒体耗氧率的降低与右心室Tei指数的升高呈负相关。这些结果表明，线粒体能量产生能力的损害参与了单苦参碱诱导的肺动脉高压大鼠右心衰的发展。
The present study was undertaken to explore the possible involvement of alterations in the mitochondrial energy-producing ability in the development of the right ventricular failure in monocrotaline-administered rats. The rats at the 6th week after subcutaneous injection of 60 mg/kg monocrotaline revealed marked myocardial hypertrophy and fibrosis, that is, severe cardiac remodeling. The time-course study on the cardiac hemodynamics of the monocrotaline-administered rat by the cannula and echocardiographic methods showed a reduction in cardiac double product, a decrease in cardiac output index, and an increase in the right ventricular Tei index, suggesting that the right ventricular failure was induced at the 6th week after monocrotaline administration in rats. The mitochondrial oxygen consumption rate of the right ventricular muscle isolated from the monocrotaline-administered animal was decreased, which was associated with a reduction in myocardial high-energy phosphates. Furthermore, the decrease in mitochondrial oxygen consumption rate was inversely related to the increase in the right ventricular Tei index of the monocrotaline-administered rats. These results suggest that impairment of the mitochondrial energy-producing ability is involved in the development of the right ventricular failure in monocrotaline-induced pulmonary hypertensive rats.