title: Iron chelation with a deferoxamine conjugate in hemorrhagic shock.
abstract: Oxygen-derived radicals are cytotoxic, highly reactive molecules that contribute to cellular death and injury in hemorrhagic shock. Iron released into the plasma in hemorrhagic shock may contribute to cellular damage by catalyzing lipid peroxidation of cell membranes. Deferoxamine (DFO) chelation of transitional metal ions prevents formation of these radicals and may diminish reperfusion injury. The conjugation of DFO to pentastarch (PS) decreases DFO toxicity and extends its half-life making it a potentially useful resuscitative fluid. A porcine hemorrhagic shock model was used to evaluate the effects of five resuscitative fluids on survival and hepatic function. Swine (11-16 kg) underwent splenectomy, liver biopsy, and placement of arterial and venous catheters. Awake animals were bled at 1 ml/kg/min to a MAP of 45 mm Hg, maintained for 1 hr, and resuscitated over 30 min with one of five fluids: Lactated Ringer's (LR); LR + free DFO 2.5 mg/ml (LR + DFO) (n = 6); 5% PS in LR (PS) (n = 6); 5% PS + free DFO (PS + DFO) 7.5 mg/ml (n = 6); 5% PS/DFO conjugate (7.5 mg/ml) in LR (n = 6). LR and LR + DFO received 3 ml/ml shed blood; PS, PS + DFO, and PS/DFO received 1 ml/ml shed blood. No shed blood was returned to the animals. There was no significant differences between groups in MAP, HR, CVP, and T pre- and post-resuscitation. No LR lived to sacrifice at 24 hr. Thirty-three percent of LR + DFO and PS + DFO animals died within minutes of receiving the free DFO containing resuscitative fluid, presumably from acute DFO toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Surgery, Hennepin County Medical Center, Minneapolis, Minnesota 55415.
authors.forename: D M
authors.initials: DM
authors.lastname: Jacobs
authors.forename: J M
authors.initials: JM
authors.lastname: Julsrud
authors.forename: M P
authors.initials: MP
authors.lastname: Bubrick
mesh_terms: D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002614:Chelating Agents / Q000494:pharmacology*; D003676:Deferoxamine / Q000494:pharmacology*; D006439:Hemodynamics; D006895:Hydroxyethyl Starch Derivatives / Q000494:pharmacology*; D007501:Iron; D008099:Liver / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D016019:Survival Analysis; D013552:Swine; D013997:Time Factors
chemical_list: D002614:Chelating Agents; D006895:Hydroxyethyl Starch Derivatives; C068460:hydroxyethyl starch-deferoxamine conjugate; D008315:Malondialdehyde; D007501:Iron; D001219:Aspartate Aminotransferases; D003676:Deferoxamine