title: Ischemia-reperfusion injury-induced pulmonary mitochondrial damage.
abstract: BACKGROUND
  Mitochondrial dysfunction is a key factor in solid organ ischemia-reperfusion (IR) injury. Impaired mitochondrial integrity predisposes to cellular energy depletion, free radical generation, and cell death. This study analyzed mitochondrial damage induced by warm pulmonary IR.
  
  
  METHODS
  Anesthetized Wistar rats received mechanical ventilation. Pulmonary clamping was followed by reperfusion to generate IR injury. Rats were subjected to control, sham, and to 2 study group conditions: 30 minutes of ischemia without reperfusion (IR30/0), or ischemia followed by 60 minutes of reperfusion (IR30/60). Pulmonary edema was quantified by wet/dry-weight ratio. Polarography determined activities of respiratory chain complexes. Mitochondrial viability was detected by using Ca(2+)-induced swelling, and integrity by citrate synthase assay. Enzyme-linked immunosorbent assay determined cytochrome C content. Mitochondrial membrane potential (ΔΨm) stability was analyzed by flow cytometry using JC1, inflammation by myeloperoxidase (MPO) activity, and matrix-metalloproteinase-9 (MMP-9) activity by gel zymography, respectively.
  
  
  RESULTS
  In IR30/60 rats, tissue water content was elevated from 80.6 % (sham) to 86.9%. After ischemia, ΔΨm showed hyperpolarization and rapid decline after uncoupling compared with controls. IR, but not ischemia alone, impaired respiratory chain function complexes I, II and III (p < 0.05). Mitochondrial viability (p < 0.001) and integrity (p < 0.01) was impaired after ischemia and IR, followed by mitochondrial cytochrome C loss (p < 0.05). Increased activation of MPO (p < 0.01) and MMP-9 (p < 0.001) was induced by reperfusion after ischemia.
  
  
  CONCLUSIONS
  Ischemia-related ΔΨm hyper-polarization induces reperfusion-associated mitochondrial respiratory chain dysfunction in parallel with tissue inflammation and degradation. Controlling ΔΨm during ischemia might reduce IR injury.
authors.affiliation: Department of Cardiothoracic- and Thoracic Vascular Surgery, University Hospital Würzburg, Würzburg, Germany. sommer_s1@klinik.uni-wuerzburg.de
authors.forename: Sebastian-Patrick
authors.initials: SP
authors.lastname: Sommer
authors.forename: Stefanie
authors.initials: S
authors.lastname: Sommer
authors.forename: Bhanu
authors.initials: B
authors.lastname: Sinha
authors.forename: Jakob
authors.initials: J
authors.lastname: Wiedemann
authors.forename: Christoph
authors.initials: C
authors.lastname: Otto
authors.forename: Ivan
authors.initials: I
authors.lastname: Aleksic
authors.forename: Christoph
authors.initials: C
authors.lastname: Schimmer
authors.forename: Rainer G
authors.initials: RG
authors.lastname: Leyh
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D008171:Lung Diseases / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D028361:Mitochondrial Diseases / Q000209:etiology* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications* / Q000503:physiopathology