title: [The nitric oxide metabolism in the hypoxic, ischemic and reperfused human skeletal muscle cell: clinical and therapeutical observations].
abstract: BACKGROUND
  The biochemical and metabolic role played by nitric oxide (NO) in course of oxidative stress due to cell hypoxia, ischemia and reperfusion has a determinant relevance in the mitochondrial adaptive changes which antagonize the irreversible morpho-functional damage. In particular conditions, such as in prolonged ischemia and/or exogenous NO supplementation, this element is present in the radical form (NOO*) concurring to peroxidative cell injury. Aim of this study was to investigate these opposite NO aspects in hypoxic, ischemic and reperfused human skeletal muscle tissue.
  
  
  METHODS
  Skeletal muscle samples were taken during elective knee orthopedic surgery in 10 consecutive patients. The biopsies were obtained before, after 5+/-1 min and 58+/-2 min from tourniquet application and then after 18+/-3 min following muscle reperfusion. The samples, immediately frozen in liquid nitrogen, were assayed for endocellular free NO following the gas-amperometric method described by Palmerini C.
  
  
  RESULTS
  When compared with normoxic tissues, a significant decrease in free NO content was observed in hypoxic samples. After about 60 min of prolonged ischemia the NO levels show an evident increase, while the tissue reperfusion leads to a progressive restoration of physiological content in the cellular free nitric oxide.
  
  
  CONCLUSIONS
  The obtained data in hypoxic muscle cell seem to underline the pivotal role played by NO in adapting the cytochrome c oxidase oxidative activity to lower O2 bio-availability. On the other hand the prolonged ischemia leads to a consistent NOO* generation triggered by oxyradical generation and Ca2+ intracellular over load. Even if the tissue reoxygenation restores the normal NO levels it is arguable that the pre-treatment of ischemic cell with antioxidants, Ca-antagonist and Dexamethasone supplementation could represent a crucial and specific therapeutic approach to critically ill patient.
authors.affiliation: Istituto di Anestesia-Rianimazione, Università degli Studi, Cagliari, Italy.
authors.forename: G G
authors.initials: GG
authors.lastname: Corbucci
authors.forename: C
authors.initials: C
authors.lastname: Palmerini
authors.forename: R
authors.initials: R
authors.lastname: Palombari
authors.forename: B
authors.initials: B
authors.lastname: Lettieri
authors.forename: E
authors.initials: E
authors.lastname: Grella
authors.forename: C
authors.initials: C
authors.lastname: Velluti
authors.forename: C
authors.initials: C
authors.lastname: Chelo
mesh_terms: D000328:Adult; D015687:Cell Hypoxia; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007511:Ischemia / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000166:cytology / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D012039:Regional Blood Flow; D015424:Reperfusion
chemical_list: D009569:Nitric Oxide