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Intensive Care Medicine
Published in: Intensive Care Medicine 8/2006

01-08-2006 | Experimental

DTPA Fe(III) decreases cytokines and hypotension but worsens survival with Escherichia coli sepsis in rats

Authors: Yan Li, Xuemei Li, Michael Haley, Yvonne Fitz, Eric Gerstenberger, Steven M. Banks, Peter Q. Eichacker, Xizhong Cui

Published in: Intensive Care Medicine | Issue 8/2006

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Abstract

Objective

Nonselective inhibition of nitric oxide (NO) with NO synthase antagonists decreases hypotension but worsens outcome clinically. We investigated whether iron (III) complex of diethylenetriaminepentaacetic acid [DTPA Fe(III)], a scavenger of NO as well as other oxidant mediators, has similar divergent effects in E. coli challenged rats.

Methods

Animals with venous and arterial catheters and challenged with intrabronchial or intravenous E. coli were randomized to treatment with DTPA Fe(III) in doses from 3 to 800 mg/kg or placebo. Mean blood pressure (MBP) was measured in all animals and plasma NO, cytokines, and blood and lung leukocyte and bacteria counts in animals administered intrabronchial E. coli and DTPA Fe(III) 50 mg/kg or placebo. Animals received antibiotics and were observed 168 h.

Results

Independent of drug regimen or infection site, compared to placebo, DTPA Fe(III) increased MBP although this was greater with high vs. lower doses. Despite increased MBP, DTPA Fe(III) worsened the hazards ratio of survival . At 6 and 24 h DTPA Fe(III) decreased NO but not significantly and decreased four cytokines (tumor necrosis factor-α, interleukins 1 and 10, and macrophage inflammatory protein 3α) and lung lavage neutrophils. From 6 to 24 h DTPA Fe(III) increased blood bacteria.

Conclusions

DTPA Fe(III) while increasing blood pressure has the potential to worsen outcome in sepsis. Further preclinical testing is required before this agent is applied clinically.
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Metadata
Title
DTPA Fe(III) decreases cytokines and hypotension but worsens survival with Escherichia coli sepsis in rats
Authors
Yan Li
Xuemei Li
Michael Haley
Yvonne Fitz
Eric Gerstenberger
Steven M. Banks
Peter Q. Eichacker
Xizhong Cui
Publication date
01-08-2006
Publisher
Springer-Verlag
Published in
Intensive Care Medicine / Issue 8/2006
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-006-0234-2

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