Ischemic preconditioning preserves mitochondrial membrane potential and limits reactive oxygen species production

Ricardo Quarrie, Daniel S. Lee, Gregory Steinbaugh, Brandon Cramer, Warren Erdahl, Douglas R. Pfeiffer, Jay L. Zweier, Juan A. Crestanello

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Mitochondrial superoxide radical (O2 ) production increases after cardiac ischemia/reperfusion (IR). Ischemic preconditioning (IPC) preserves mitochondrial function and attenuates O2 production, but the mechanism is unknown. Mitochondrial membrane potential (mΔΨ) is known to affect O 2 production; mitochondrial depolarization decreases O2 formation. We examined the relationship between O2 production and mΔΨ during IR and IPC. Materials/methods: Rat hearts were subjected to Control or IPC. Mitochondria were isolated at end equilibration (End EQ), end ischemia (End I), and end reperfusion (End RP). mΔΨ was measured using a tetraphenylphosphonium electrode. Mitochondrial O2 production was measured by electron paramagnetic resonance using DMPO spin trap. Cytochrome c levels were measured using high-pressure liquid chromatography. Results: IPC preserved mΔΨ at End I (-156 ± 5 versus -131 ± 6 mV, P <0.001) and End RP (-168 ± 2 versus -155 ± 2 mV, P <0.05). At End RP, IPC attenuated O2 production (2527 ± 221 versus 3523 ± 250 AU/mg protein, P <0.05). IPC preserved cytochrome c levels (351 ± 14 versus 269 ± 16 picomoles/mg protein, P <0.05) at End RP, and decreased mitochondrial cristae disruption (10% ± 4% versus 33% ± 7%, P <0.05) and amorphous density formation (18% ± 4% versus 28% ± 1%, P <0.05). Conclusion: We conclude that IPC preserves mΔΨ, possibly by limiting disruption of mitochondrial inner membrane. IPC also decreases mitochondrial O2 production and preserves mitochondrial ultrastructure after IR. While it was previously held that slight decreases in mΔΨ decrease O 2 production, our results indicate that preservation of mΔΨ is associated with decreased O2 and preservation of cardiac function in IPC. These findings indicate that the mechanism of IPC may not involve mΔΨ depolarization, but rather preservation of mitochondrial electrochemical potential.

Original languageEnglish (US)
Pages (from-to)8-17
Number of pages10
JournalJournal of Surgical Research
Volume178
Issue number1
DOIs
StatePublished - Nov 2012
Externally publishedYes

Keywords

  • Cardiac
  • Heart
  • Ischemia/reperfusion
  • Ischemic preconditioning
  • Membrane potential
  • Mitochondria
  • Reactive oxygen species

ASJC Scopus subject areas

  • Surgery

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