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l-Arginine supplementation in hyperdynamic endotoxemic pigs: Effect on nitric oxide synthesis by the different organs*

Bruins, Maaike J. PhD; Soeters, Peter B. MD, PhD; Lamers, Wouter H. MD, PhD; Meijer, Alfred J. PhD; Deutz, Nicolaas E. P. MD, PhD


Objectives  Under septic conditions, the protective role of nitric oxide in the organs may become compromised at a time of increased demand as a result of decreased availability of l-arginine. It remains unknown whether supplementation with l-arginine, as a substrate, can modulate organ nitric oxide production.

Design  Controlled study with laboratory animals.

Setting  University research laboratory.

Subjects  Female crossbred pigs.

Intervention  Pigs were challenged with Escherichia coli endotoxin (intravenously) and received intravenous fluid resuscitation for 24 hrs to reproduce a model of long-lasting hyperdynamic endotoxemia. Pigs were infused with either l-arginine or l-alanine intravenously during endotoxin and via the intragastric route after cessation of endotoxin infusion. The effects of l-arginine supplementation on nitric oxide synthesis and the relationships with arginine metabolism were determined with a stable isotope infusion protocol. Also, organ nitrite plus nitrate fluxes were measured. Implantation of multiple catheters enabled in vivo measurements across the hindquarter muscle, the portal-drained viscera, the liver, and the kidneys.

Measurements and Results  The isotope conversion method showed that l-arginine intervention significantly increased nitric oxide production by the portal-drained viscera, liver, and kidneys, resulting in elevated whole-body nitric oxide synthesis under endotoxemic and postendotoxemic conditions. Organ nitrite plus nitrate fluxes only tended to increase because of high variance among data.

Conclusions  In this endotoxemia model, supplemental use of l-arginine favored nitric oxide synthesis in various organs.

From the Department of Surgery (MJB, PBS, NEPD), Maastricht University, Maastricht, The Netherlands; and the Departments of Anatomy & Embryology (WHL) and Biochemistry (AJM), University of Amsterdam, Amsterdam, the Netherlands.

*See also p. 705.

Supported, in part, by grant 902-23-098 from the Netherlands Organization for Scientific Research.

In this endotoxemia model, supplemental use of l-arginine favored nitric oxide synthesis in various organs.

© 2002 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins