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The peroxynitrite catalyst WW-85 improves pulmonary function in ovine septic shock
Dirk M Maybauer1, Marc O Maybauer, Csaba Szabó
1Departments of Anesthesiology, Pathology, and Surgery, Investigational Intensive Care Unit, The University of Texas Medical Branch and Shriners Burns Hospital for Children, Galveston, Texas, USA. dmmaybau@utmb.edu
Shock (Augusta, Ga.)
|June 26, 2010
Summary
WW-85, a peroxynitrite decomposition catalyst, significantly improved lung function and reduced cellular injury in a sheep model of septic shock. This indicates blocking the nitric oxide-peroxynitrite pathway is a promising therapeutic strategy.
Area of Science:
- Biomedical Sciences
- Physiology
- Pharmacology
Background:
- Systemic inflammatory response syndrome involves excessive nitric oxide (NO·) and superoxide (O2) production, leading to harmful peroxynitrite formation.
- Peroxynitrite is a key mediator of cellular damage, causing necrosis and apoptosis in conditions like acute lung injury and septic shock.
Purpose of the Study:
- To investigate the therapeutic potential of WW-85, a peroxynitrite decomposition catalyst, in a sheep model of acute lung injury and septic shock.
- To evaluate the impact of blocking the nitric oxide-peroxynitrite pathway on physiological disturbances and cellular injury.
Main Methods:
- Eighteen sheep were divided into sham, control, and WW-85 treatment groups.
- Acute lung injury and septic shock were induced using cotton smoke and Pseudomonas aeruginosa instillation.
- WW-85 was administered via bolus and continuous infusion following injury induction.
Main Results:
- WW-85 treatment significantly improved gas exchange and reduced airway obstruction and shunt formation.
- Treated animals showed reduced markers of oxidative stress and inflammation, including myeloperoxidase, malondialdehyde, and 3-nitrotyrosine.
- WW-85 administration led to decreased microvascular leakage and enhanced pulmonary function.
Conclusions:
- Blockade of the nitric oxide-peroxynitrite pathway using WW-85 effectively mitigates the detrimental effects of septic shock.
- The findings in this clinically relevant ovine model suggest WW-85 as a potential therapeutic agent for sepsis-induced lung injury.
