title: Remote and local ischemic preconditioning equivalently protects rat skeletal muscle mitochondrial function during experimental aortic cross-clamping.
abstract: OBJECTIVE
  This study investigated whether remote (rIPC) and local ischemic preconditioning (IPC) similarly limit skeletal muscle dysfunction induced by aortic cross-clamping.
  
  
  METHODS
  Rats were divided in three groups: the sham-operated control group (C) underwent surgery without clamping. The ischemia-reperfusion group (IR) had 3 hours of ischemia induced by aortic clamping and collateral vessels ligation, followed by 2 hours of reperfusion. The IPC group had, before prolonged ischemia, three bouts of 10 minutes of ischemia and 10 minutes of reperfusion on the right hind limb. Thus, right hind limbs had local IPC and left hind limbs had rIPC. Complexes I, II, III, and IV activities of the mitochondrial respiratory chain of the gastrocnemius muscle were measured using glutamate-malate (V(max)), succinate (V(succ)), and N,N,N',N'-tetramethyl-p-phenylenediamine dihydrochloride (TMPD)-ascorbate (V(TMPD)). Expressions of genes involved in apoptosis (Bax, Bcl-2) and antioxidant defense (superoxide dismutase 1 [SOD 1], SOD2, glutathione peroxidase [GPx]) were determined by quantitative real-time polymerase chain reaction. Glutathione was also measured.
  
  
  RESULTS
  Right and left hind limb mitochondrial functions were similar in controls and after IR. IR reduced V(max) (-21.2%, 6.6 ± 1 vs 5.2 ± 1 μmol O(2)/min/g dry weight, P = .001), V(succ) (-22.2%, P = .032), and V(TMPD) (-22.4%, P = .033), and increased Bax (63.4%, P = .020) and Bax/Bcl-2 ratio (+84.6%, P = .029). SODs and GPx messenger RNA were not modified, but glutathione tended to be decreased after IR. Local IPC and rIPC counteracted similarly these deleterious effects, restoring mitochondrial maximal oxidative capacities and normalizing Bax, the Bax/Bcl-2 ratio, and glutathione.
  
  
  CONCLUSIONS
  Remote ischemic preconditioning protection against IR injury is equivalent to that achieved by local IPC. It might deserve a broader use in clinical practice.
  
  
  CONCLUSIONS
  Acute and chronic ischemia induce mitochondrial dysfunction in human skeletal muscles, and improving muscle mitochondrial function improves subjects’ status. Compared with local ischemic preconditioning (IPC), remote IPC (rIPC) appears easier to perform and is safer for the vessel and territory involved in ischemic injury. This study demonstrates that the muscle protection afforded by rIPC is equivalent to that achieved by IPC. Acknowledging that IPC procedures should be specifically adapted to patient characteristics to be successful, our results support a broader use of rIPC in the setting of vascular surgery.
authors: Service de Chirurgie Cardiovasculaire, Pôle de Cardiologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors: Ziad
authors: Z
authors: Mansour
authors: Jamal
authors: J
authors: Bouitbir
authors: Anne Laure
authors: AL
authors: Charles
authors: Samy
authors: S
authors: Talha
authors: Michel
authors: M
authors: Kindo
authors: Julien
authors: J
authors: Pottecher
authors: Joffrey
authors: J
authors: Zoll
authors: Bernard
authors: B
authors: Geny
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000601:surgery*; D019069:Cell Respiration; D003250:Constriction; D019610:Cytoprotection; D004195:Disease Models, Animal; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D004734:Energy Metabolism; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics; D006614:Hindlimb; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism* / Q000473:pathology; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D013997:Time Factors; D014656:Vascular Surgical Procedures / Q000009:adverse effects*; D051028:bcl-2-Associated X Protein / Q000235:genetics; D000099156:Superoxide Dismutase 2
chemical_list: D045222:Electron Transport Chain Complex Proteins; D005978:Glutathione; D005979:Glutathione Peroxidase; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D051028:bcl-2-Associated X Protein; D000099156:Superoxide Dismutase 2; C494828:Bax protein, rat; C000606290:SOD1 protein, human; C000606292:Sod1 protein, rat