Abstract
Ischemic preconditioning (IPC) before sustained ischemia (ISC) decreases infarct size. We found that reversible chemical blockade of electron transport at complex I immediately before sustained ISC preserves mitochondrial respiration and decreases infarct size during ISC-reperfusion. We proposed that IPC would decrease complex I activity and attenuate state 3 respiration through complex I as a potential mechanism of cardioprotection. Langendorff-perfused rat hearts underwent IPC (3 cycles 5 min 37°C global ISC and 5 min reperfusion) or were perfused for 40 min without ISC as time controls. Subsarcolemmal (SSM) and interfibrillar (IFM) populations of mitochondria were isolated to measure respiration (natom O/min/mg protein) with complex I substrates (glutamate or pyruvate-malate). Maximally-expressed complex I activity (nmol NADH/min/mg) was measured as NADH:ubiquinone oxidoreductase in detergent-solubilized mitochondria. IPC did not decrease state 3 respiration. Complex I activity was also unaffected by IPC. IPC increased state 4 respiration in IFM (59 ± 7, n=6 vs 41 ± 5, n=5, p<0.05) indicating decreased coupling of respiration. Thus, the protection of IPC does not occur via a decrease in complex I activity or a decrease in respiration through complex I during subsequent sustained ISC. Alternatively, IPC decreases the coupling of respiration as a potential mechanism of cardioprotection.
Published Version
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