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. 2011 Aug;37(5):842-50.
doi: 10.1016/j.burns.2010.12.020. Epub 2011 Feb 22.

The peroxynitrite catalyst WW-85 improves microcirculation in ovine smoke inhalation injury and septic shock

Dirk M Maybauer  1 , Marc O Maybauer, Csaba Szabó, Martin Westphal, Lillian D Traber, Andrew L Salzman, David N Herndon, Daniel L Traber
Affiliations

The peroxynitrite catalyst WW-85 improves microcirculation in ovine smoke inhalation injury and septic shock

Dirk M Maybauer et al. Burns. 2011 Aug.

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.

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Conflict of interest statement

Conflict of interest

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Hemodynamic changes after smoke inhalation injury and bacterial challenge (1A) MAP, mean arterial pressure, mmHg; and 1(B) HR, heart rate, beats/min. Data are expressed as mean ± SEM of 7 animals per group.
Fig. 2
Fig. 2
Regional microvascular blood flow (RMBF) 2(A) Cerebellum; 2(B) Cerebral cortex; 2(C) Ileum; and 2(D) Kidneys. Baseline blood flow = normal organ blood flow (100%), changes in blood flow as percentage from baseline. Significance: p<0.05, #vs. baseline, *vs. control, †vs. sham.
See this image and copyright information in PMC

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