Nakahara T, Takeo S
Can J Cardiol. 1986 Jan-Feb;2(1):24-33.
The present study was designed to elucidate irreversible biochemical changes in the mitochondrial membrane of hearts subjected to hypoxia and subsequent reoxygenation in a rabbit heart Langendorff preparation. Significant changes in the mitochondrial calcium uptake, ATPase, and oxidative phosphorylation activities were seen in the heart receiving 30 to 60 min of hypoxic perfusion. These changes were accompanied by deleterious alterations in contractile function. Among hypoxia-induced changes in biochemical activities of isolated mitochondria, only oxidative phosphorylation activity was found to be irreversible upon reoxygenation. This is compatible with the findings of reoxygenation-induced incomplete recovery of tissue ATP level, once decreased by hypoxic perfusion. In the electron microscopic study, the heart receiving 60 min of hypoxic perfusion showed contracted sarcomeres, vacuolization and electron lucency of the mitochondria which were not restored by the subsequent reoxygenation. The results suggest that an inability of the mitochondrial membrane to produce high-energy phosphate primarily induces lack of ATP required for cardiac mechanical activity and membrane integrity, which in turn leads to the impairment of myocardial cell function.
本研究旨在阐明在兔心脏Langendorff标本中，经历缺氧及随后复氧的心脏线粒体膜中不可逆的生化变化。在接受30至60分钟缺氧灌注的心脏中，观察到线粒体钙摄取、ATP酶和氧化磷酸化活性有显著变化。这些变化伴随着收缩功能的有害改变。在缺氧诱导的分离线粒体生化活性变化中，只有氧化磷酸化活性在复氧后被发现是不可逆的。这与缺氧灌注导致组织ATP水平降低后，复氧诱导组织ATP水平不完全恢复的结果一致。在电子显微镜研究中，接受60分钟缺氧灌注的心脏显示肌节收缩、线粒体空泡化和电子透明，随后的复氧并未使其恢复。结果表明，线粒体膜无法产生高能磷酸主要导致心脏机械活动和膜完整性所需的ATP缺乏，进而导致心肌细胞功能受损。
