title: Cardiomyocyte mitochondria as targets of humoral factors released by remote ischemic preconditioning.
abstract: BACKGROUND
  Remote ischemic preconditioning (RIPC) reduces myocardial infarct size, and protection can be transferred with plasma to other individuals, even across species. Mitochondria are the end-effectors of cardioprotection by local ischemic conditioning maneuvers. We have now analyzed mitochondrial function in response to RIPC.
  
  
  METHODS
  Plasma from pigs undergoing placebo or RIPC (infarct size reduction by 67% in RIPC pigs compared to placebo) was transferred to isolated perfused rat hearts subjected to 30 min global ischemia followed by 120 min reperfusion for infarct size measurement. Additional experiments were terminated at 10 min reperfusion to isolate mitochondria for functional measurements. Effects of RIPC pig plasma were compared to local ischemic preconditioning (IPC) or to infusion of tumor necrosis factor α (TNF-α).
  
  
  RESULTS
  Ischemia/reperfusion (I/R) induced an infarct of 41 ±2% of total ventricular mass. Placebo pig plasma did not affect infarct size (38 ±1,p= 0.13). The RIPC pig plasma reduced infarct size (27 ±2,p< 0.001), as did IPC (20 ±1,p< 0.001) and TNF-α (28 ±2,p< 0.001). Associated with cardioprotection, reductions of mitochondrial adenosine diphosphate (ADP)-stimulated respiration, adenosine triphosphate (ATP) production and calcium retention capacity (CRC) by I/R and placebo pig plasma were prevented by RIPC pig plasma, as they were by IPC and TNF-α. Mitochondrial reactive oxygen species production (nmol H2O2/100 µg protein) induced by I/R (272 ±34) was comparable in response to placebo pig plasma (234 ±28,p= 0.37) and was reduced by RIPC pig plasma (83 ±15,p< 0.001) as well as by IPC (78 ±21,p< 0.001) and TNF-α (125 ±42,p= 0.002).
  
  
  CONCLUSIONS
  In rat myocardium, mitochondria are an intracellular target of protection induced by humoral factors retrieved from pigs undergoing RIPC.
authors.affiliation: Institute for Pathophysiology, West German Heart and Vascular Centre Essen, University of Essen, Medical School, Essen, Germany.
authors.forename: Nilguen
authors.initials: N
authors.lastname: Gedik
authors.affiliation: Institute for Pathophysiology, West German Heart and Vascular Centre Essen, University of Essen, Medical School, Essen, Germany; Laboratory of Cardiac Electrophysiology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Maciel
authors.affiliation: Institute for Pathophysiology, West German Heart and Vascular Centre Essen, University of Essen, Medical School, Essen, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Schulte
authors.affiliation: Institute for Pathophysiology, West German Heart and Vascular Centre Essen, University of Essen, Medical School, Essen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Skyschally
authors.affiliation: Institute for Pathophysiology, West German Heart and Vascular Centre Essen, University of Essen, Medical School, Essen, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Heusch
authors.affiliation: Institute for Pathophysiology, West German Heart and Vascular Centre Essen, University of Essen, Medical School, Essen, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Kleinbongard
keywords: cardioprotection; humoral factor; mitochondria; remote ischemic preconditioning