title: The peroxynitrite catalyst WW-85 improves microcirculation in ovine smoke inhalation injury and septic shock.
abstract: This prospective, randomized, controlled experimental study examined the effects of the peroxynitrite decomposition catalyst WW-85 on global hemodynamics and regional microvascular blood flow (RMBF) in an established ovine model of septic shock following severe smoke inhalation injury. Twenty-one sheep were randomized into a sham group (no injury), a control group (smoke/sepsis), and a treatment group (smoke/sepsis/WW-85; n=7 each). WW-85 was administered 1h after injury as a bolus (0.1 mg/kg), followed by a continuous infusion of 0.02 mg/kg/h RMBF was analyzed using colored microspheres. All control animals developed a hypotensive, hyperdynamic circulation and increased plasma levels of nitrate/-nitrite (NOx). All hemodynamic variables and NOx levels were significantly improved in the treatment group. In visceral organs of controls, blood flow to trachea, ileum, and spleen significantly increased (p<0.05). Blood flow to kidneys and pancreas significantly decreased (p<0.05). Treatment with WW-85 stabilized blood flow to ileum, spleen, and kidneys on baseline levels and was significantly improved compared to controls (p<0.05). Cerebral blood flow deteriorated in controls, but was significantly improved in cerebral cortex, cerebellum, pons, medulla oblongata, and thalamus (p<0.05) by WW-85. These results provide evidence that WW-85 blocks NO production, thereby improving cardiovascular function and microcirculation.
authors.affiliation: Department of Anesthesiology, Investigational Intensive Care Unit, The University of Texas Medical Branch and Shriners Burns Hospital for Children at Galveston, Galveston, TX 77555-0591 , USA.
authors.forename: Dirk M
authors.initials: DM
authors.lastname: Maybauer
authors.forename: Marc O
authors.initials: MO
authors.lastname: Maybauer
authors.forename: Csaba
authors.initials: C
authors.lastname: Szabó
authors.forename: Martin
authors.initials: M
authors.lastname: Westphal
authors.forename: Lillian D
authors.initials: LD
authors.lastname: Traber
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Salzman
authors.forename: David N
authors.initials: DN
authors.lastname: Herndon
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Traber
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002384:Catalysis; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000187:drug effects; D008833:Microcirculation / Q000187:drug effects*; D009589:Nitrogen Oxides / Q000097:blood; D030421:Peroxynitrous Acid / Q000494:pharmacology*; D011446:Prospective Studies; D011897:Random Allocation; D012039:Regional Blood Flow / Q000187:drug effects*; D034561:Sheep, Domestic; D012772:Shock, Septic / Q000503:physiopathology*; D015208:Smoke Inhalation Injury / Q000503:physiopathology*
chemical_list: D009589:Nitrogen Oxides; C506898:WW85 compound; D030421:Peroxynitrous Acid