title: Remote ischemic preconditioning elaborates a transferable blood-borne effector that protects mitochondrial structure and function and preserves myocardial performance after neonatal cardioplegic arrest.
abstract: OBJECTIVE
  Remote ischemic preconditioning is known to elicit production of a blood-borne cardioprotective factor that is infarct sparing in models of ischemia-reperfusion injury and myocardial damage reducing after cardiopulmonary bypass in human subjects. The mechanism of protection remains incompletely understood. In this study, we examined effects on mitochondrial structure and function in a noninfarct model of cardioplegic arrest.
  
  
  METHODS
  Explanted neonatal rabbit hearts were mounted in a Langendorff preparation and perfused with dialysate of blood taken from sham-treated or remotely preconditioned rabbits. Each heart was subsequently subjected to 1-hour cardioplegic arrest and 30-minute reperfusion periods, during which hemodynamic responses were measured. Mitochondria were isolated for structural and functional measurements.
  
  
  RESULTS
  Relative to hearts with sham-treated dialysate, myocardial performance (systolic pressure, maximum positive and negative first derivatives of left ventricular pressure, and left ventricular end-diastolic pressure) was better preserved with dialysate from preconditioned rabbits. Similarly, mitochondria isolated from hearts with dialysate from preconditioned rabbits showed preserved respiration at complex I and IV in the electron transport chain (P < .01 and P < .05, respectively). Mitochondrial outer membrane integrity was also preserved, with diminished sensitivity of mitochondrial respiration to exogenous cytochrome c (P < .01) and less cytosolic diffusion of cytochrome c (P < .01). Mitochondrial resistance to calcium-mediated mitochondrial permeability transition pore opening was not affected.
  
  
  CONCLUSIONS
  The cardioprotective factor in plasma dialysate after remote preconditioning preserves mitochondrial structure and function in a noninfarct cardioplegic arrest model. This protection is associated with preservation of global myocardial performance.
authors.affiliation: Division of Cardiovascular Research, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Lixing
authors.initials: L
authors.lastname: Wang
authors.forename: Norihiko
authors.initials: N
authors.lastname: Oka
authors.forename: Michael
authors.initials: M
authors.lastname: Tropak
authors.forename: John
authors.initials: J
authors.lastname: Callahan
authors.forename: John
authors.initials: J
authors.lastname: Lee
authors.forename: Greg
authors.initials: G
authors.lastname: Wilson
authors.forename: Andrew
authors.initials: A
authors.lastname: Redington
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Caldarone
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents / Q000378:metabolism*; D045304:Cytochromes c / Q000378:metabolism / Q000494:pharmacology; D006324:Heart Arrest, Induced; D006439:Hemodynamics; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D008929:Mitochondria, Heart / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D015425:Myocardial Reperfusion; D010101:Oxygen Consumption; D010539:Permeability; D011817:Rabbits; D016277:Ventricular Function, Left
chemical_list: D002316:Cardiotonic Agents; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D045304:Cytochromes c; D002118:Calcium