Janati-Idrissi R, Besson B, Laplace M, Bui M H
INSERM U400, Faculté de Médicine, Creteil, France.
Basic Res Cardiol. 1995 Jul-Aug;90(4):305-13. doi: 10.1007/BF00797908.
Little comparative information is available on mitochondrial function changes during experimentally-induced hypertrophy. Respiratory control mechanisms are not exactly the same in situ and in isolated mitochondria. This study assessed in situ mitochondrial function in two myocardial hypertrophy models.
Cytochrome aa3 (Cytaa3) and myoglobin (Mb) absorption changes were monitored in isolated rat hearts using dual wavelength spectrophotometry (Cytaa3: 605-630 nm, Mb: 581-592 nm). Hypertrophy was induced by creation of an aortic stenosis or of an aorto-caval fistula. Optical monitoring was performed on diastole-arrested perfused hearts using the sequence O2 perfusion, N2 perfusion during 4 min, and reoxygenation. The plateaus of the Cytaa3 and Mb curves were used to quantify oxidation-reduction and oxygenation levels. Respiratory kinetics were characterized by the slopes of transition phase curves.
Myoglobin oxygenation was comparable in the hypertrophied and control hearts. However, Cytaa3 oxidation-reduction levels in the hypertrophied hearts showed a shift towards greater reduction in comparison with the controls (controls: 0.580 +/- 0.008 DO605/DO630 nm, n = 34; fistula: 0.530 +/- 0.023, n = 23; stenosis: 0.522 +/- 0.016, n = 20, p < 0.001). The rate of Cytaa3 reduction and the rate of myoglobin deoxygenation were significantly accelerated (p < 0.005) in the volume overload group (0.507 +/- 0.043, n = 23), whereas the respiratory rate in the pressure overload group (0.389 +/- 0.034, n = 20) was comparable to that in the control hearts (0.358 +/- 0.026 delta DO 605 nm/DO630 nm.min-1, n = 34).
We found mitochondrial function alterations in both volume overload- and pressure overload-induced cardiac hypertrophy, despite adequate cytosol oxygenation. The patterns of these alterations differed: the redox state showed a shift of similar magnitude toward greater reduction in both models, but the respiratory rate was increased in the volume-overloaded hearts and unchanged in the pressure-overloaded hearts. The modification in the oxidation-reduction state suggested that overload hypertrophy may induce changes in the metabolism of the myocardium, which may, in turn, load to persistent modifications in mitochondrial function. The differences between the two models suggest that adaptation to hypertrophy-inducing events exists at the level of the mitochondrion.
关于实验性诱导肥大过程中线粒体功能变化的比较信息较少。原位和分离线粒体中的呼吸控制机制并不完全相同。本研究评估了两种心肌肥大模型中的原位线粒体功能。
使用双波长分光光度法（细胞色素aa3（Cytaa3）：605 - 630nm，肌红蛋白（Mb）：581 - 592nm）监测离体大鼠心脏中细胞色素aa3和肌红蛋白的吸收变化。通过创建主动脉狭窄或主动脉 - 腔静脉瘘诱导肥大。对舒张期停搏的灌注心脏进行光学监测，采用O2灌注、4分钟的N2灌注和再氧合的顺序。Cytaa3和Mb曲线的平台用于量化氧化还原和氧合水平。呼吸动力学通过过渡相曲线的斜率来表征。
肥大心脏和对照心脏中的肌红蛋白氧合相当。然而，与对照相比，肥大心脏中的细胞色素aa3氧化还原水平向更大程度的还原方向偏移（对照：0.580±0.008 DO605/DO630nm，n = 34；瘘管：0.530±0.023，n = 23；狭窄：0.522±0.016，n = 20，p < 0.001）。容量超负荷组（0.507±0.043，n = 23）中细胞色素aa3的还原速率和肌红蛋白的脱氧速率显著加快（p < 0.005），而压力超负荷组（0.389±0.034，n = 20）的呼吸速率与对照心脏（0.358±0.026 ΔDO 605nm/DO630nm·min-1，n = 34）相当。
我们发现，尽管胞质有充足的氧合，但在容量超负荷和压力超负荷诱导的心脏肥大中均存在线粒体功能改变。这些改变的模式不同：两种模型中氧化还原状态均向更大程度的还原方向发生了相似幅度的偏移，但容量超负荷心脏的呼吸速率增加，而压力超负荷心脏的呼吸速率未改变。氧化还原状态的改变表明超负荷肥大可能诱导心肌代谢变化，进而可能导致线粒体功能的持续改变。两种模型之间的差异表明，线粒体水平存在对肥大诱导事件的适应性。
