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: Dirk M Maybauer, Marc O Maybauer, Csaba Szabó, Martin Westphal, Lillian D Traber, Andrew L Salzman, David N Herndon, Daniel L Traber
• Journal: Burns : journal of the International Society for Burn Injuries (Burns) Vol. 37 Issue 5 Pg. 842-50 (Aug 2011) ISSN: 1879-1409 [Electronic] Netherlands
• PMID: 21345593 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd and ISBI. All rights reserved.

Chemical References

• Nitrogen Oxides
• WW85 compound
• Peroxynitrous Acid

Topics

• Animals
• Blood Pressure (drug effects)
• Catalysis
• Disease Models, Animal
• Hemodynamics (drug effects)
• Microcirculation (drug effects)
• Nitrogen Oxides (blood)
• Peroxynitrous Acid (pharmacology)
• Prospective Studies
• Random Allocation
• Regional Blood Flow (drug effects)
• Sheep, Domestic
• Shock, Septic (physiopathology)
• Smoke Inhalation Injury (physiopathology)