Effects of Hydroxyethyl Starch-Deferoxamine on Arachidonic Acid Metabolism and Small Bowel Wall Perfusion in Early Sepsis

Abstract

The effects of hydroxyethyl starch-conjugated deferoxamine (HES-DFO), a macromolecular iron chelator, were investigated on eicosanoid release and bowel wall perfusion following cecal ligation puncture (CLP) in rats. Animals were randomly given an intravenous dose of 3.0 ml of HES-DFO or either vehicle (HES) or 9.0 ml saline immediately following completion of the CLP procedure. At 30,60,120, and 240 min after sepsis induction, blood pressure and bowel perfusion were measured. The animals were sacrificed and blood was collected for subsequent analysis of thromboxane, prostacyclin, and prostaglandin F_2α. The tissue content of energy-rich phosphates was determined in small-bowel samples at each time point. The antioxidative HES-DFO therapy did not diminish the eicosanoid release after CLP when compared with either HES-treated or saline-infused rats. However, treatment with the polymeric iron chelator resulted in an impaired bowel wall perfusion that was not reflected in alterations in total adenine nucleotide content or in energy charge. Considering hemodynamic and biochemical endpoints, these results are contradictory to the hypothesis that iron-driven oxygen radicals are major determinants of the eicosanoid release that is elevated following CLP-induced sepsis.

Key Words:

• cecal ligation puncture
• deferoxarnine
• eicosanoids
• endotoxin
• energy-rich phosphates
• hydroxyethyl starch
• iron chelation
• laser Doppler flowmetry
• oxygen radicals
• prostacyclin
• prostaglandin F_2α
• rats
• sepsis
• thromboxane