Protection of hearts from reperfusion injury by propofol is associated with inhibition of the mitochondrial permeability transition
Protection of hearts from reperfusion injury by propofol is associated with inhibition of the mitochondrial permeability transition
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DOI：
10.1016/s0008-6363(99)00365-x
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发表时间：
2000-01-14
影响因子：
10.8
通讯作者：
Halestrap, AP
中科院分区：
文献类型：
--
作者：
Javadov, SA;Lim, KHH;Halestrap, AP
目的：减少氧化应激可能通过阻止线粒体通透性转换孔的打开来保护心脏免受缺血再灌注损伤。全身麻醉剂异丙酚是一种自由基清除剂，研究了其对全身和心脏麻痹性缺血停搏后MPT和心脏保护作用的影响。方法：在异丙酚存在或不存在的情况下，对离体Wister大鼠心脏进行暖性全脑缺血（Langendorff）或冷性圣托马斯心脏骤停（工作心脏模式）。采用[H-3]-2-脱氧葡萄糖-6-磷酸（[H-3]-DOG-6P）包埋法测定MPT孔隙开度。分离线粒体的呼吸功能也被确定为氧化应激的证据。结果：异丙酚（2 μ g/ml）可显著改善Langendorff心脏再灌注后的功能恢复（左室发展压由28.4+/-6.2降至53.3+/-7.3 mmHg，左室舒张末期压由52.9+/-4.3降至37.5+/-3.9 mmHg）。异丙酚（4 μ g/ml）处理的工作心脏在冷性心脏骤停后恢复也有所改善。与对照组相比，体外心脏再灌注功从0.42+/-0.05提高到0.60+/-0.03 J/s，为基线值的45-64%
Objective: Diminishing oxidative stress may protect the heart against ischaemia-reperfusion injury by preventing opening of the mitochondrial permeability transition (MPT) pore. The general anaesthetic agent propofol, a free radical scavenger, has been investigated for its effect on the MPT and its cardioprotective action following global and cardioplegic ischaemic arrest. Method: Isolated perfused Wister rat hearts were subjected to either warm global ischaemia (Langendorff) or cold St. Thomas' cardioplegia (working heart mode) in the presence or absence of propofol. MPT pore opening was determined using [H-3]-2-deoxyglucose-6-phosphate ([H-3]-DOG-6P) entrapment. The respiratory function of isolated mitochondria was also determined for evidence of oxidative stress. Results: Propofol (2 mu g/ml) significantly improved the functional recovery of Langendorff hearts on reperfusion (left ventricular developed pressure from 28.4+/-6.2 to 53.3+/-7.3 mmHg and left ventricular end diastolic pressure from 52.9+/-4.3 to 37.5+/-3.9 mmHg). Recovery was also improved in propofol (4 mu g/ml) treated working hearts following cold cardioplegic arrest. External cardiac work on reperfusion improved from 0.42+/-0.05 to 0.60+/-0.03 J/s, representing 45-64% of baseline values, when compared to controls (P