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CRITICAL CARE AND TRAUMA

Selective Inducible Nitric Oxide Inhibition Can Restore Hemodynamics, but Does Not Improve Neurological Dysfunction in Experimentally-Induced Septic Shock in Rats

Yuji Kadoi, MD^*, and Fumio Goto, MD

*Department of Intensive Care, Gunma University, School of Medicine, Gunma, Japan; and Department of Anesthesiology, Gunma University, Graduate School of Medicine, Gunma, Japan

Address correspondence and reprint requests to Yuji Kadoi, MD, Department of Intensive Care, Gunma University, School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan. Address e-mail to kadoi{at}med.gunma-u.ac.jp

In this study, we evaluated the time course of changes in inducible nitric oxide synthase (iNOS) in the brain by using the rat model of sepsis induced by cecal ligation and puncture (CLP) and examined whether selective iNOS inhibition can prevent the hemodynamic and neurological changes induced by sepsis. Male Wistar rats were randomly divided into four groups: control, sham, CLP, and CLP + the selective iNOS inhibitor L-N6-(1-iminoethyl)-lysine (L-NIL). Septic shock was induced in the rats by CLP under pentobarbital anesthesia, and then we measured hemodynamic variables, neurological indicators, blood gases, plasma levels of nitrate/nitrite (an indicator of the biosynthesis of NO), and brain iNOS activity and nitrotyrosine levels after 1, 6, 12, and 24 h. Plasma nitrite was increased at 12 and 24 h in the CLP group. The activity of iNOS in the brain was increased at 12 and 24 h after CLP (at 12 h: control, 0.3 ± 0.05; sham, 0.3 ± 0.1; CLP, 1.3 ± 0.08*; CLP + L-NIL, 0.33 ± 0.1 fmol · mg^–1 · min^–1; at 24 h: control, 0.27 ± 0.08; sham, 0.31 ± 0.1; CLP, 1.0 ± 0.3*; CLP + L-NIL, 0.34 ± 0.1 fmol · mg^–1 · min^–1; mean ± SD; *P < 0.05). Brain nitrotyrosine was increased at 24 h after CLP (at 24 h: control, 6.7 ± 0.4; sham, 6.7 ± 0.5; CLP, 11.2 ± 2.8*; CLP + L-NIL, 7.52 ± 0.5 densitometric units; means ± SD; *P < 0.01). In contrast, in both the CLP and CLP + L-NIL groups, the consciousness reflex was significantly decreased at 24 h after CLP. Selective iNOS inhibition restored the hemodynamic changes induced by sepsis but could not improve neurological dysfunction.

IMPLICATIONS: We examined whether selective inducible nitric oxide synthase inhibition can prevent the neurological changes induced by sepsis and found that it could not improve neurological dysfunction.

This article has been cited by other articles:

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999