title: The severity of microvascular dysfunction due to compartment syndrome is diminished by the systemic application of CO-releasing molecule-3.
abstract: OBJECTIVE
  To examine the protective effects of carbon monoxide (CO), liberated from a novel CO-releasing molecule (CORM-3), on the function of compartment syndrome (CS)-challenged muscle in a rodent model, thus providing for a potential development of a pharmacologic adjunctive treatment for CS.
  
  
  METHODS
  Wistar rats were randomized into 4 groups: sham (no CS), CS, CS with inactive CORM-3 (iCORM-3), and CS + CORM-3 (10 mg/kg intraperitoneally). CS was induced by elevation of intracompartmental pressure to 30 mm Hg through an infusion of isotonic saline into the anterior compartment of the hind limb for 2 hours. Both CORM-3 and iCORM-3 were injected immediately after fasciotomy. Microvascular perfusion, cellular tissue injury, and inflammatory response within the extensor digitorum longus muscle were assessed using intravital video microscopy 45 minutes after fasciotomy. Systemic levels of tumor necrosis factor alpha (TNF-α) were also measured.
  
  
  RESULTS
  Elevation of intracompartmental pressure resulted in significant microvascular perfusion deficits (23% ± 2% continuously perfused capillaries in CS vs. 76% ± 4% in sham, P < 0.0001; 55% ± 2% nonperfused capillaries in CS vs. 13% ± 2% in sham, P < 0.0001), significant increase in tissue injury (ethidium bromide/bisbenzimide of 0.31 ± 0.05 in CS vs. 0.05 ± 0.03 in sham, P < 0.0001) and adherent leukocytes (13.7 ± 0.9 in CS vs. 1.8 ± 0.5 in sham, P < 0.0001), and a progressive rise in systemic TNF-α. CORM-3 (but not iCORM-3) treatment restored the number of continuously perfused capillaries (57% ± 5%, P < 0.001), diminished tissue injury (ethidium bromide/bisbenzimide of 0.07 ± 0.01, P < 0.001), reversed the CS-associated rise in TNF-α, and decreased leukocyte adherence (0.6 ± 0.3, P < 0.001).
  
  
  CONCLUSIONS
  CORM-3 displays a potent protective/anti-inflammatory action in an experimental model of CS, suggesting a potential therapeutic application to patients at risk of developing CS.
authors.affiliation: *Division of Orthopaedic Surgery, University of Western Ontario, London, Ontario, Canada; †Centre for Critical Illness Research, Lawson Health Research Institute, London, Ontario, Canada; and ‡Department of Medical Biophysics, University of Western Ontario, London, Ontario, Canada.
authors.forename: Abdel-Rahman
authors.initials: AR
authors.lastname: Lawendy
authors.forename: Aurelia
authors.initials: A
authors.lastname: Bihari
authors.forename: David W
authors.initials: DW
authors.lastname: Sanders
authors.forename: Richard F
authors.initials: RF
authors.lastname: Potter
authors.forename: Gediminas
authors.initials: G
authors.lastname: Cepinskas
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects*; D002196:Capillaries / Q000187:drug effects / Q000503:physiopathology*; D002199:Capillary Permeability / Q000187:drug effects*; D003161:Compartment Syndromes / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D007274:Injections, Intraperitoneal; D008297:Male; D055806:Microvessels / Q000187:drug effects / Q000503:physiopathology*; D009942:Organometallic Compounds / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
chemical_list: D009942:Organometallic Compounds; C476530:tricarbonylchloro(glycinato)ruthenium(II)