Low-pressure reperfusion alters mitochondrial permeability transition
Low-pressure reperfusion alters mitochondrial permeability transition
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DOI：
10.1152/ajpheart.01081.2004
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发表时间：
2005-06-01
影响因子：
4.8
通讯作者：
Ferrera, R
中科院分区：
文献类型：
--
作者：
Bopassa, JC;Michel, P;Ferrera, R
我们假设低压再灌注可能通过抑制线粒体通透性转换孔（mPTP）开放来限制心肌坏死并减轻缺血后收缩功能障碍。雄性 Wistar 大鼠心脏 (n = 36) 根据 Langendorff 技术进行灌注，暴露于 40 分钟缺血，并分配到以下组之一：1) 常压再灌注 (NP = 100 cmH(2)O) 或 2) 低压再灌注 (LP = 70 cmH2O)。使用肌酸激酶释放和氯化四苯基四唑染色来评估梗塞面积。通过冠脉流量、心率 (HR)、左心室展开压 (LVDP)、压力曲线的一阶导数 (dP/dt) 和心率-压力乘积 (RPP = LVDP x HR) 的变化来评估心功能的改变。从再灌注心肌中分离线粒体，并使用电位法测量 Ca2+ 诱导的 mPTP 开放。通过测量丙二醛的产生来评估脂质过氧化。 LP 组的梗塞面积显着减小，平均为 NP 组左心室重量的 17 +/- 3%，而 NP 组为 33 +/- 3%。再灌注结束时，LP 心脏的功能恢复显着改善，RPP 平均为 10,392 +/- 876，而 NP 心脏为 3,969 +/- 534 mmHg/min (P < 0.001)。 LP 和 NP 心脏中诱导 mPTP 打开所需的 Ca2+ 负荷平均分别为 232 +/- 10 和 128 +/- 16 muM（P < 0.001）。 LP 心脏中的心肌丙二醛显着低于 NP 心脏（P < 0.05）。这些结果表明，低压再灌注提供的保护涉及抑制 mPTP 的开放，可能是通过减少活性氧的产生来实现的。
We hypothesized that low-pressure reperfusion may limit myocardial necrosis and attenuate postischemic contractile dysfunction by inhibiting mitochondrial permeability transition pore (mPTP) opening. Male Wistar rat hearts (n = 36) were perfused according to the Langendorff technique, exposed to 40 min of ischemia, and assigned to one of the following groups: 1) reperfusion with normal pressure (NP = 100 cmH(2)O) or 2) reperfusion with low pressure (LP = 70 cmH2O). Creatine kinase release and tetraphenyltetrazolium chloride staining were used to evaluate infarct size. Modifications of cardiac function were assessed by changes in coronary flow, heart rate (HR), left ventricular developed pressure (LVDP), the first derivate of the pressure curve (dP/dt), and the rate-pressure product (RPP = LVDP x HR). Mitochondria were isolated from the reperfused myocardium, and the Ca2+-induced mPTP opening was measured using a potentiometric approach. Lipid peroxidation was assessed by measuring malondialdehyde production. Infarct size was significantly reduced in the LP group, averaging 17 +/- 3 vs. 33 +/- 3% of the left ventricular weight in NP hearts. At the end of reperfusion, functional recovery was significantly improved in LP hearts, with RPP averaging 10,392 +/- 876 vs. 3,969 +/- 534 mmHg/min in NP hearts (P < 0.001). The Ca2+ load required to induce mPTP opening averaged 232 +/- 10 and 128 +/- 16 mu M in LP and NP hearts, respectively (P < 0.001). Myocardial malondialdehyde was significantly lower in LP than in NP hearts (P < 0.05). These results suggest that the protection afforded by low-pressure reperfusion involves an inhibition of the opening of the mPTP, possibly via reduction of reactive oxygen species production.