title: Deferoxamine and hespan complex as a resuscitative adjuvant in hemorrhagic shock rat model.
abstract: The optimal type and amount of fluid for resuscitation of injured patients in hemorrhagic hypovolemic shock remains controversial. Use of deferoxamine, an iron chelator and oxygen-free radical scavenger, and hespan (hydroxyethyl starch), a colloid plasma expander, was evaluated in a rat hemorrhagic shock model. Eighty Sprague-Dawley male rats were utilized in four experiments. In these rats, bi-femoral cutdowns were performed for blood withdrawal, resuscitation, blood sampling, and continuous blood pressure monitoring. All rats, except control (with bilateral cutdown only), were bled and maintained at 40 mmHg for 90 min. The shed blood was returned and animals were resuscitated. One hour later, 2 mg/kg lidocaine was injected and blood samples were taken at 10, 15, 30, and 60 min for evaluation of lidocaine derivative monoethylglycinexylidide (MEGX) by fluorescent polarization immunoassay. In experiment 1 (n = 31), resuscitation with different volumes of Ringer's lactate (7.5 mL, 15.0 mL, and 30.0 mL/kg) was compared and 7.5 mL/kg LR was most beneficial. In experiment 2 (n = 22), resuscitation with three doses of Hespan (3.75 mL, 7.5 mL, and 15 mL/kg) was compared. A dose of 15 mL/kg significantly improved the liver function. In experiment 3 (n = 15), resuscitations with two doses of deferoxamine (30 mg and 100 mg/kg) were compared. A dose of 100 mg/kg significantly improved the liver function. In experiment 4 (n = 12), a combination of deferoxamine (100 mg/kg) and Hespan (3.75 and 7.5 mL) was used. Deferoxamine (100 mg/kg) complexed with 7.5 mL of Hespan was found the most beneficial resuscitation. This conjugate could be a choice as a resuscitative adjuvant in hypovolemic shock without any side effects.
authors.affiliation: Department of Anatomy, Saint Louis University Health Sciences Center, Missouri 63104, USA.
authors.forename: M Waheed
authors.initials: MW
authors.lastname: Rana
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Shapiro
authors.forename: M Arif
authors.initials: MA
authors.lastname: Ali
authors.forename: Yao-Jan
authors.initials: YJ
authors.lastname: Chang
authors.forename: William H
authors.initials: WH
authors.lastname: Taylor
mesh_terms: D000818:Animals; D003676:Deferoxamine / Q000008:administration & dosage*; D006895:Hydroxyethyl Starch Derivatives / Q000008:administration & dosage*; D007502:Iron Chelating Agents / Q000008:administration & dosage*; D007552:Isotonic Solutions / Q000008:administration & dosage; D008012:Lidocaine / Q000031:analogs & derivatives*; D008102:Liver Circulation / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation / Q000379:methods; D000077325:Ringer's Lactate; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D006895:Hydroxyethyl Starch Derivatives; D007502:Iron Chelating Agents; D007552:Isotonic Solutions; D000077325:Ringer's Lactate; C068460:hydroxyethyl starch-deferoxamine conjugate; D008012:Lidocaine; C001173:monoethylglycinexylidide; D003676:Deferoxamine