Remote ischemic preconditioning elaborates a transferable blood borne factor which protects mitochondrial structure and function and preserves myocardial performance after neonatal cardioplegic arrest
Norihiko Oka, Lixing Wang, Michael Tropek, John Callahan, Gregory Wilson, Andrew Redington, Christopher A. Caldarone; Hospital for Sick Children, Toronto, ON, Canada
Comment on this Abstract
Objective: Remote ischemic preconditioning is known to elicit production of a blood borne cardioprotective factor with infarct-sparing effects in models of ischemia-reperfusion injury. The mechanism of protection remains incompletely understood. In this study we examine the effects of the cardioprotective factor on mitochondrial structure and function in a non-infarct model of cardioplegic arrest.
Methods: Explanted neonatal rabbit hearts were mounted in a Langendorf preparation. The hearts were perfused with a dialysate of blood taken from another group of rabbits which were sham-treated or remotely preconditioned. Each heart was subsequently subjected to 1 hour of cardioplegic arrest and 30 minutes of reperfusion during which hemodynamic responses were measured. Mitochondria were then isolated for structural and functional measurements.
Results: Compared to hearts treated with the sham-treated dialysate, myocardial performance (systolic pressure, maximum positive dP/dT, negative dP/dT, and LVEDP) was better preserved after treatment with dialysate from preconditioned rabbits. Similarly, mitochondria isolated from hearts treated with the dialysate from preconditioned rabbits showed preserved respiration at complex I and IV in the electron transport chain (P<0.01 and P<0.05 respectively). Mitochondrial outer membrane integrity was also preserved with diminished sensitivity of mitochondrial respiration to exogenous cytochrome c (P<0.01) and less diffusion of cytochrome c into the cytosol (P<0.01). Mitochondrial resistance to calcium-mediated mPTP opening was not affected.
Conclusion: The cardioprotective factor present in plasma dialysate following remote preconditioning preserves mitochondrial structure and function in a non-infarct cardioplegic arrest model. This protection is associated with preservation of global myocardial performance.
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