Nitric oxide synthase inhibition in sepsis? Lessons learned from large-animal studies

Hauser, B., Bracht, H., Matejovic, M., Radermacher, P. and Venkatesh, B. (2005) Nitric oxide synthase inhibition in sepsis? Lessons learned from large-animal studies. Anesthesia and Analgesia, 101 2: 488-498. doi:10.1213/01.ANE.0000177117.80058.4D

Author Hauser, B.
Bracht, H.
Matejovic, M.
Radermacher, P.
Venkatesh, B.
Title Nitric oxide synthase inhibition in sepsis? Lessons learned from large-animal studies
Journal name Anesthesia and Analgesia   Check publisher's open access policy
ISSN 0003-2999
Publication date 2005-08
Sub-type Article (original research)
DOI 10.1213/01.ANE.0000177117.80058.4D
Volume 101
Issue 2
Start page 488
End page 498
Total pages 11
Editor R. D. Miller
Place of publication Philadelphia, PA, U.S.A.
Publisher Lippincott Williams & Wilkins
Collection year 2005
Language eng
Subject C1
321009 Intensive Care
730100 Clinical (Organs, Diseases and Abnormal Conditions)
Abstract Nitric Oxide (NO) plays a controversial role in the pathophysiology of sepsis and septic shock. Its vasodilatory effects are well known, but it also has pro- and antiinflammatory properties, assumes crucial importance in antimicrobial host defense, may act as an oxidant as well as an antioxidant, and is said to be a vital poison for the immune and inflammatory network. Large amounts of NO and peroxynitrite are responsible for hypotension, vasoplegia, cellular suffocation, apoptosis, lactic acidosis, and ultimately multiorgan failure. Therefore, NO synthase (NOS) inhibitors were developed to reverse the deleterious effects of NO. Studies using these compounds have not met with uniform success however, and a trial using the nonselective NOS inhibitor N-G-methyl-L-arginine hydrochloride was terminated prematurely because of increased mortality in the treatment arm despite improved shock resolution. Thus, the issue of NOS inhibition in sepsis remains a matter of debate. Several publications have emphasized the differences concerning clinical applicability of data obtained from unresuscitated, hypodynamic rodent models using a pretreatment approach versus resuscitated, hyperdynamic models in high-order species using posttreatment approaches. Therefore, the present review focuses on clinically relevant large-animal studies of endotoxin or living bacteria-induced, hyperdynamic models of sepsis that integrate standard day-today care resuscitative measures.
Keyword Anesthesiology
Smoke-inhalation Injury
Acute lung injury
Hypoxic pulmonary vasoconstriction
Placebo-controlled multicenter
Arginine hydrochloride 546c88
Septic shock
Porcine endotoxemia
Anesthetized pigs
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
2006 Higher Education Research Data Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 57 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 77 times in Scopus Article | Citations
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Created: Wed, 15 Aug 2007, 06:02:23 EST