• Yan Li, Xuemei Li, Michael Haley, Yvonne Fitz, Eric Gerstenberger, Steven M Banks, Peter Q Eichacker, and Xizhong Cui.
• Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
• Intensive Care Med. 2006 Aug 1;32(8):1263-70.

ObjectiveNonselective 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.MethodsAnimals 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.ResultsIndependent 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-alpha, interleukins 1 and 10, and macrophage inflammatory protein 3alpha) and lung lavage neutrophils. From 6 to 24 h DTPA Fe(III) increased blood bacteria.ConclusionsDTPA 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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