期刊
CARDIOVASCULAR RESEARCH
卷 77, 期 2, 页码 406-415出版社
OXFORD UNIV PRESS
DOI: 10.1016/j.cardiores.2007.08.008
关键词
mitochondria; energy metabolism; free radicals; ischaemia; reperfusion
资金
- NHLBI NIH HHS [HL 073246-01] Funding Source: Medline
- NIA NIH HHS [2P01AG15885] Funding Source: Medline
- PHS HHS [0355608Z, 0425037B] Funding Source: Medline
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.
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