title: Postconditioning modulates ischemia-damaged mitochondria during reperfusion.
abstract: Cardiac ischemia damages the mitochondrial electron transport chain and the damage persists during reperfusion. Ischemic postconditioning (PC), applied during early reperfusion, decreases cardiac injury. This finding suggests that the ischemia-damaged mitochondria can be regulated to decrease cardiac injury. The reversible blockade of electron transport during ischemia prevents damage to mitochondria. We propose that the targets of PC cytoprotective signaling are mitochondria damaged by ischemia. Thus, if ischemia-mediated mitochondrial damage is prevented, PC at the onset of reperfusion will not result in additional protection. Isolated, Langendorff-perfused adult rat hearts underwent 25-minute global ischemia and 30-minute reperfusion. Amobarbital (2.5 mM) was used to reversibly inhibit electron transport during ischemia. PC (6 cycles of 10-second ischemia-reperfusion) was applied at the onset of reperfusion. Subsarcolemmal and interfibrillar mitochondria were isolated after reperfusion. Blockade of electron transport with amobarbital only during ischemia preserved oxidative phosphorylation and decreased myocardial injury. PC, after untreated ischemia, decreased cardiac injury without improvement of oxidative phosphorylation. Blockade of electron transport during ischemia or PC improved calcium tolerance and inner membrane potential in subsarcolemmal mitochondria after reperfusion. In hearts treated with amobarbital before ischemia, PC did not provide further protection. Thus, PC protects myocardium via the regulation of ischemia-damaged mitochondria during early reperfusion.
authors.affiliation: Division of Cardiology, Department of Medicine, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Qun
authors.initials: Q
authors.lastname: Chen
authors.forename: Melanie
authors.initials: M
authors.lastname: Paillard
authors.forename: Ludovic
authors.initials: L
authors.lastname: Gomez
authors.forename: Heng
authors.initials: H
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Lesnefsky
mesh_terms: D000654:Amobarbital / Q000494:pharmacology; D000818:Animals; D004579:Electron Transport / Q000187:drug effects; D066298:In Vitro Techniques; D057775:Ischemic Postconditioning; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D010085:Oxidative Phosphorylation; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D000654:Amobarbital