Improved mitochondrial bioenergetics by anesthetic preconditioning during and after 2 hours of 27°C ischemia in isolated hearts
Improved mitochondrial bioenergetics by anesthetic preconditioning during and after 2 hours of 27°C ischemia in isolated hearts
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DOI：
10.1097/01.fjc.0000175238.18702.40
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发表时间：
2005-09-01
影响因子：
3
通讯作者：
Stowe, DF
中科院分区：
文献类型：
--
作者：
An, JZ;Camara, AKS;Stowe, DF
我们研究了在完整心脏冷缺血（麻醉预处理，APC）前给予七氟烷是否通过进一步改善线粒体能量平衡提供额外的保护，以及是否被线粒体K-ATP阻滞剂消除。在5组离体豚鼠心脏的左心室壁内测量NADH和FAD荧光：（1）单独低温;（2）低温+缺血;（3）APC（4.1%七氟醚）+冷缺血;（4）5-HD +冷缺血;和（5）APC + 5-HD +冷缺血。将心脏暴露于七氟烷15分钟，然后在冷却前在37 ℃下冲洗15分钟，在27 ℃下缺血2小时，在37 ℃下再灌注2小时。K-ATP通道抑制剂5-HD在七氟醚前、后灌注。缺血引起NADH的快速增加和FAD的减少，其在2小时内减弱。热再灌注导致NADH减少和FAD增加。APC减弱了NADH和FAD的变化，进一步改善了缺血后功能，缩小了梗死面积。5-HD阻断APC的心肌保护作用，但不能阻断APC诱导的NADH和FAD的改变。因此，APC改善氧化还原平衡，并具有轻度低温缺血的心脏保护作用。5-HD阻断APC诱导的心脏保护作用，但不能改善线粒体生物能量学。这表明在冷缺血和再灌注过程中通过K-ATP通道开放的保护作用是APC诱导的氧化还原状态改善的下游，或者这些氧化还原状态的变化不会被K-ATP通道拮抗作用减弱。
We examined if sevoflurane given before cold ischemia of intact hearts (anesthetic preconditioning, APC) affords additional protection by further improving mitochondrial energy balance and if this is abolished by a mitochondrial K-ATP blocker. NADH and FAD fluorescence was measured within the left ventricular wall of 5 groups of isolated guinea pig hearts: (1) hypothermia alone; (2) hypothermia + ischemia; (3) APC (4.1% sevoflurane) + cold ischemia; (4) 5-HD + cold ischemia, and (5) APC + 5-HD + cold ischemia. Hearts were exposed to sevoflurane for 15 minutes followed by 15 minutes of washout at 37 degrees C before cooling, 2 hours of 27 degrees C ischemia, and 2 hours of 37 degrees C reperfusion. The K-ATP channel inhibitor 5-HD was perfused before and after sevoflurane. Ischemia caused a rapid increase in NADH and a decrease in FAD that waned over 2 hours. Warm reperfusion led to a decrease in NADH and an increase in FAD. APC attenuated the changes in NADH and FAD and further improved postischemic function and reduced infarct size. 5-HD blocked the cardioprotective effects of APC but not APC-induced alterations of NADH and FAD. Thus, APC improves redox balance and has additive cardioprotective effects with mild hypothermic ischemia. 5-HD blocks APC-induced cardioprotective effects but not improvements in mitochondrial bioenergetics. This suggests that mediation of protection by K-ATP channel opening during cold ischemia and reperfusion is downstream from the APC-induced improvement in redox state or that these changes in redox state are not attenuated by K-ATP channel antagonism.