Hyperoxia confers myocardial protection in mechanically ventilated rats through the generation of free radicals and opening of mitochondrial ATP-sensitive potassium channels
Hyperoxia confers myocardial protection in mechanically ventilated rats through the generation of free radicals and opening of mitochondrial ATP-sensitive potassium channels
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DOI：
10.1111/j.1440-1681.2007.04745.x
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发表时间：
2008-01-01
影响因子：
2.9
通讯作者：
Fiore, Tommaso
中科院分区：
文献类型：
--
作者：
Colantuono, Giuseppe;Tiravanti, Edy Altea;Fiore, Tommaso
1. 先前已经证明，暴露于高氧环境一小时可以限制自发呼吸大鼠随后的缺血再灌注损伤。我们测试了机械通气期间较短时间的高氧对心脏的保护作用，以及活性氧（ROS）和线粒体ATP敏感钾（mitoK(ATP)）通道的可能贡献。将机械通气大鼠置于常氧（FiO2 = 0.3）或高氧（FiO2 = 1.0）条件下30 min，分别在机械通气30 min时和30 min后测量pH、Pco(2)、Po-2、心率、气道和血压。离体心脏随后进行30分钟缺血和120分钟再灌注。测量梗死面积、左室舒张末压（LVEDP）、发展压（LVDP）和冠状动脉血流（CF）。为了研究ROS和K-ATP通道在心脏保护机制中的作用，机械通气大鼠输注自由基清除剂n -乙酰半胱氨酸（NAC, 150 mg/kg），离体心脏缺血前立即输注K-ATP通道阻滞剂格列本脲（200 mmol/L）或5-羟乙酸酯（10 mmol/L）。两组间Pco(2)、pH、心率、气道及血压均无差异。高氧组Po-2极显著高于常氧组（P < 0.01）。缺血30min后，我们发现与常氧组相比，高氧预处理显著改善了CF （P < 0.01）、LVDP （P < 0.01）和LVEDP (P < 0.01)，降低了再灌注心脏梗死面积（P < 0.01）。3 .大鼠在高氧通气前给予NAC或缺血前给予K-ATP通道阻滞剂，心肌保护作用消失。缺血前高氧机械通气可减少心肌再灌注损伤。这可能是通过诱导氧化应激发生的，氧化应激导致肌细胞mitoK（ATP）通道打开。
1. One hour exposure to hyperoxia has been shown previously to limit a subsequent ischaemia-reperfusion injury in spontaneously breathing rats. We tested the cardioprotective effect of a shorter period of hyperoxia during mechanical ventilation and the possible contribution of reactive oxygen species (ROS) and mitochondrial ATP-sensitive potassium (mitoK(ATP)) channels.2. Mechanically ventilated rats were exposed to normoxia (FiO2 = 0.3) or hyperoxia (FiO2 = 1.0) for 30 min and pH, Pco(2), Po-2, heart rate, airway and blood pressure were measured at baseline and after 30 min mechanical ventilation. Isolated hearts were subsequently subjected to 30 min ischaemia and 120 min reperfusion. Infarct size and left ventricular end-diastolic pressure (LVEDP), developed pressure (LVDP) and coronary flow (CF) were measured. In order to investigate the role of ROS and K-ATP channels within the mechanism leading to cardioprotection, the free radical scavenger N-acetylcysteine (NAC; 150 mg/kg) was infused in mechanically ventilated rats and the K-ATP channel blockers glibenclamide (200 mmol/L) or 5-hydroxydecanoate (10 mmol/L) were infused in isolated hearts immediately before ischaemia.3. No differences were detected in Pco(2), pH, heart rate, airway and blood pressure between the groups. However, the Po-2 in hyperoxic groups was significantly higher compared with that in normoxic groups (P < 0.01). After 30 min ischaemia, we found that hyperoxic preconditioning significantly improved CF (P < 0.01), LVDP (P < 0.01) and LVEDP (P < 0.01) and reduced the extent of infarct size in the reperfused heart compared with the normoxic group (P < 0.01). When rats were pretreated either with NAC before hyperoxic ventilation or with K-ATP channel blockers before ischaemia, myocardial protection was abolished.4. Hyperoxic mechanical ventilation, prior to ischaemia, reduces myocardial reperfusion injury. This is likely to occur through the induction of oxidative stress, which leads to myocyte mitoK(ATP) channel opening.