EFFECTS OF HYDROXYETHYL STARCH-DEFEROXAMINE ON ARACHIDONIC-ACID METABOLISM AND SMALL-BOWEL WALL PERFUSION IN EARLY SEPSIS

The effects of hydroxyethyl starch-conjugated deferoxamine (HES-DFO), a macromolecular iron chelator, were investigated on eicosanoid releas e 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 co mpletion of the CLP procedure. At 30, 60, 120, and 240 min after sepsi s induction, blood pressure and bowel perfusion were measured. The ani mals were sacrificed and blood was collected for subsequent analysis o f thromboxane, prostacyclin, and prostaglandin F-2 alpha. The tissue c ontent of energy-rich phosphates was determined in small-bowel samples at each time point. The antioxidative HES-DFO therapy did not diminis h the eicosanoid release after CLP when compared with either HES-treat ed or saline-infused rats. However, treatment with the polymeric iron chelator resulted in an impaired bowel wall perfusion that was not ref lected in alterations in total adenine nucleotide content or in energy charge. Considering hemodynamic and biochemical endpoints, these resu lts are contradictory to the hypothesis that iron-driven oxygen radica ls are major determinants of the eicosanoid release that is elevated f ollowing CLP-induced sepsis.