Inhibited mitochondrial respiration by amobarbital during cardiac ischaemia improves redox state and reduces matrix Ca2+ overload and ROS release
Inhibited mitochondrial respiration by amobarbital during cardiac ischaemia improves redox state and reduces matrix Ca2+ overload and ROS release
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DOI：
10.1016/j.cardiores.2007.08.008
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发表时间：
2008-01-15
影响因子：
10.8
通讯作者：
Camara, Amadou K. S.
中科院分区：
文献类型：
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作者：
Aidakkak, Mohammed;Stowe, David F.;Camara, Amadou K. S.
目的缺血时线粒体电子传递链（ETC）发生损伤。阻断电子流的ETC缺血前可逆的复合物I抑制剂异戊巴比妥保护孤立的线粒体缺血性损伤，并保留氧化磷酸化和细胞色素c的内容。我们假设，在缺血前短暂的异戊巴比妥灌注可以通过保护线粒体氧化还原状态和减少线粒体超氧化物来改善心脏缺血和再灌注（IR）后的恢复并减少梗死面积（O-2（-中心点））的产生，反过来又会减少线粒体Ca 2+的积累方法豚鼠Langendorff灌流心脏，分别用Krebs Ringer液（KR;未处理）或异戊巴比妥处理。(2.5 mM）在KR中持续1分钟，然后立即进行30分钟的无流动、全身缺血，随后进行再灌注而不进行另外的处理。结果异戊巴比妥钠灌流前1 min，心肌线粒体NADH、FAD、mt[Ca 2 +]和O-2（-center dot）水平明显升高，线粒体NADH、FAD水平无明显变化，mt[Ca 2 +]水平明显降低。在缺血期间，异戊巴比妥组线粒体NADH较高，O-2（-中心点）水平较低，mt[Ca 2 +]升高较少。再灌注时O-2异戊巴比妥组心内[Ca 2 +] i和mt明显降低，NADH-FAD氧化还原状态得以维持，心功能明显改善;结论异戊巴比妥暂时性阻断线粒体复合物I活性可通过减少O-2的产生而保护心脏（-中心点）和线粒体Ca（2+）负荷。
Aim Damage to the mitochondrial electron transport chain (ETC) occurs during ischaemia. Blockade of electron flow in the ETC just before ischaemia with the reversible complex I inhibitor amobarbital protects isolated mitochondria against ischaemic damage and preserves oxidative phosphorylation and cytochrome c content. We hypothesized that brief amobarbital perfusion just before ischaemia would improve cardiac recovery and decrease infarct size after ischaemia and reperfusion (IR) by preserving the mitochondrial redox state and reducing mitochondrial superoxide (O-2(-center dot)) generation, in turn would decrease mitochondrial Ca2+ accumulation (mt[Ca2+]).Methods Guinea pig Langendorff-perfused hearts were treated with Krebs Ringer solution (KR; untreated) or amobarbital. (2.5 mM) in KR for 1 min immediately before 30 min of no flow, global ischaemia, followed by reperfusion without additional treatment. Cardiac function, mitochondrial NADH, FAD, mt[Ca2+], and O-2(-center dot) levels were assessed during the 1 min perfusion period and throughout IR.Results Amobarbital perfusion atone before ischaemia significantly increased O-2(-center dot) levels and NADH, without altering FAD, and decreased mt[Ca2+]. During ischaemia, mitochondrial NADH was higher, O-2(-center dot) levels were lower, and mt[Ca2+] was less elevated in the amobarbital group. On reperfusion O-2(-center dot) levels and mt[Ca2+] were significantly reduced, NADH-FAD redox state was preserved and cardiac function was markedly improved in the amobarbital group; infarct size was smaller in the amobarbital group compared to the untreated group.Conclusion Temporary blockade of mitochondrial complex I activity by amobarbital protects hearts by reducing production of O-2(-center dot) and mtCa(2+) loading during IR injury.