A novel nitric oxide scavenger decreases liver injury and improves survival after hemorrhagic shock

John Menezes; Christian Hierholzer; Simon C. Watkins; Valerie Lyons; Andrew B. Peitzman; Timothy R. Billiar; David J. Tweardy; Brian G. Harbrecht

doi:10.1152/ajpgi.1999.277.1.g144

A novel nitric oxide scavenger decreases liver injury and improves survival after hemorrhagic shock

John Menezes, Christian Hierholzer, Simon C. Watkins, Valerie Lyons, Andrew B. Peitzman, Timothy R. Billiar, David J. Tweardy, Brian G. Harbrecht^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

79 Scopus citations

Abstract

We tested the ability of a nitric oxide (NO) scavenger to reduce tissue injury in a rodent model of hemorrhagic shock. Rats were hemorrhaged to a mean arterial blood pressure (MAP) of 40 mmHg and then resuscitated when either 30% of their shed blood had been returned (group 1) or after 100 min of continuous shock (group 2). Selected animals were treated with the NO scavenger NOX (30 mg · kg^-1 · h^-1) infused over 4 h. Hemorrhaged rats had a lower MAP after resuscitation compared with sham-shock control rats. NOX treatment significantly increased MAP after resuscitation from hemorrhage. Hemorrhagic shock also increased liver injury as reflected by elevated ornithine carbamoyltransferase (OCT) plasma levels, and NOX treatment significantly reduced OCT release. In addition, NOX was associated with significantly decreased hepatic neutrophil infiltration and improved 24- h survival (n = 8 of 9) compared with saline-treated shock animals (n = 3 of 9). These data suggest that excess NO mediates shock-induced tissue injury and that suppression of NO availability with NO scavengers may reduce the pathophysiological sequelae of severe hemorrhage.

Original language	English
Pages (from-to)	G144-G151
Journal	American Journal of Physiology - Gastrointestinal and Liver Physiology
Volume	277
Issue number	1 40-1
DOIs	https://doi.org/10.1152/ajpgi.1999.277.1.g144
State	Published - Jul 1999
Externally published	Yes

Keywords

Multiple organ failure
Nitric oxide synthase
Trauma kidney

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10.1152/ajpgi.1999.277.1.g144

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Menezes, J., Hierholzer, C., Watkins, S. C., Lyons, V., Peitzman, A. B., Billiar, T. R., Tweardy, D. J., & Harbrecht, B. G. (1999). A novel nitric oxide scavenger decreases liver injury and improves survival after hemorrhagic shock. American Journal of Physiology - Gastrointestinal and Liver Physiology, 277(1 40-1), G144-G151. https://doi.org/10.1152/ajpgi.1999.277.1.g144

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abstract = "We tested the ability of a nitric oxide (NO) scavenger to reduce tissue injury in a rodent model of hemorrhagic shock. Rats were hemorrhaged to a mean arterial blood pressure (MAP) of 40 mmHg and then resuscitated when either 30% of their shed blood had been returned (group 1) or after 100 min of continuous shock (group 2). Selected animals were treated with the NO scavenger NOX (30 mg · kg-1 · h-1) infused over 4 h. Hemorrhaged rats had a lower MAP after resuscitation compared with sham-shock control rats. NOX treatment significantly increased MAP after resuscitation from hemorrhage. Hemorrhagic shock also increased liver injury as reflected by elevated ornithine carbamoyltransferase (OCT) plasma levels, and NOX treatment significantly reduced OCT release. In addition, NOX was associated with significantly decreased hepatic neutrophil infiltration and improved 24- h survival (n = 8 of 9) compared with saline-treated shock animals (n = 3 of 9). These data suggest that excess NO mediates shock-induced tissue injury and that suppression of NO availability with NO scavengers may reduce the pathophysiological sequelae of severe hemorrhage.",

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AB - We tested the ability of a nitric oxide (NO) scavenger to reduce tissue injury in a rodent model of hemorrhagic shock. Rats were hemorrhaged to a mean arterial blood pressure (MAP) of 40 mmHg and then resuscitated when either 30% of their shed blood had been returned (group 1) or after 100 min of continuous shock (group 2). Selected animals were treated with the NO scavenger NOX (30 mg · kg-1 · h-1) infused over 4 h. Hemorrhaged rats had a lower MAP after resuscitation compared with sham-shock control rats. NOX treatment significantly increased MAP after resuscitation from hemorrhage. Hemorrhagic shock also increased liver injury as reflected by elevated ornithine carbamoyltransferase (OCT) plasma levels, and NOX treatment significantly reduced OCT release. In addition, NOX was associated with significantly decreased hepatic neutrophil infiltration and improved 24- h survival (n = 8 of 9) compared with saline-treated shock animals (n = 3 of 9). These data suggest that excess NO mediates shock-induced tissue injury and that suppression of NO availability with NO scavengers may reduce the pathophysiological sequelae of severe hemorrhage.

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A novel nitric oxide scavenger decreases liver injury and improves survival after hemorrhagic shock

Abstract

Keywords

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