title: Heterogeneity of the effects of combined nitric oxide synthase inhibition on organ perfusion in ovine sepsis.
abstract: BACKGROUND
  Previous studies demonstrated beneficial effects of early neuronal nitric oxide synthase (nNOS) and subsequent inducible NOS (iNOS) inhibition on the development of multiple organ dysfunctions in septic sheep. However, the effects of NOS inhibition on regional blood flow remained undetermined. The current study was conducted to assess the effects of combined NOS inhibition on blood flow to various organs in an ovine sepsis model.
  
  
  METHODS
  Eighteen adult, female sheep were randomly allocated to the following groups: (1) sham-injured, non-treated group, (2) injured (smoke inhalation and instillation of Pseudomonas aeruginosa into the lungs), non-treated group (control), and (3) injured, treated group (specific nNOS inhibition from 1 h to 12 h and iNOS inhibition from 12 h to 24 h post-injury). Fluorescent microspheres were injected at baseline and various time points post-injury. At the end of the 24-h experimental period, tissue from various organs was harvested.
  
  
  RESULTS
  Blood flow to the ileum was significantly increased in the control group from 12 h to 24 h versus sham (P < 0.05). This increase was attenuated in the treatment group (P < 0.05). In contrast, blood flow to the pancreas was significantly increased in the treatment group after 12 h and 24 h versus both sham and control (P < 0.05). Blood flow to the spleen was significantly lower after 24h in the control group versus sham and treatment (P < 0.05 both).
  
  
  CONCLUSIONS
  Combined NOS inhibition significantly influenced the pathologically altered organ perfusion during ovine sepsis. However, this treatment strategy showed heterogeneous effects on organ perfusion, perhaps dependent on the sepsis-related degree of NO production and ensuing changes in regional flow.
authors.affiliation: Department of Anesthesiology, Investigational Intensive Care Unit, The University of Texas Medical Branch and Shriners Hospitals for Children, Galveston, TX, USA; Department of Anesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany. Electronic address: lanm@gmx.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Lange
authors.forename: Atsumori
authors.initials: A
authors.lastname: Hamahata
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Traber
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Nakano
authors.forename: Lillian D
authors.initials: LD
authors.lastname: Traber
authors.forename: Perenlei
authors.initials: P
authors.lastname: Enkhbaatar
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D007082:Ileum / Q000098:blood supply; D007191:Indazoles; D008171:Lung Diseases / Q000188:drug therapy / Q000382:microbiology / Q000503:physiopathology; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D010179:Pancreas / Q000098:blood supply; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000503:physiopathology; D011550:Pseudomonas aeruginosa; D011897:Random Allocation; D012039:Regional Blood Flow; D018805:Sepsis / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology*; D012756:Sheep; D012757:Sheep Diseases / Q000188:drug therapy / Q000503:physiopathology*; D015208:Smoke Inhalation Injury / Q000188:drug therapy / Q000503:physiopathology; D013154:Spleen / Q000098:blood supply
chemical_list: D004791:Enzyme Inhibitors; D007191:Indazoles; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; C080122:7-nitroindazole
keywords: Inducible nitric oxide synthase; Neuronal nitric oxide synthase; Regional blood flow; Sheep