title: Iron chelation attenuates intracranial pressure and improves survival in a swine model of acute liver failure.
abstract: Oxidative mechanisms have been implicated in the pathogenesis of brain edema in acute liver failure (ALF). The aim of this study was to test the hypothesis that inhibition of iron-catalyzed oxidative reactions through iron chelation using deferoxamine could attenuate brain edema in a swine model of ischemic ALF. Following ALF induction (end-to-side portacaval anastomosis and ligation of the hepatoduodenal ligament), 14 animals were randomized to a study group that received an intravenous infusion of 150 mg/kg deferoxamine (group DF; n = 7) or a control group (group C; n = 7). Six sham-operated animals were also assigned to a deferoxamine-treated group (n = 3) or a control group (n = 3). Hemodynamic, neurological, and hematological parameters were monitored postoperatively. All sham animals maintained normal hemodynamics and intracranial pressure. At 18 hours, group DF animals had higher mean arterial pressure (mean +/- standard deviation: 98.0 +/- 15.9 versus 69.9 +/- 15.8 mmHg, P < 0.004), lower intracranial pressure (18.1 +/- 8.6 versus 32.7 +/- 13.4 mmHg, P < 0.032), and higher cerebral perfusion pressure (76.4 +/- 16.4 versus 37.1 +/- 25.6 mmHg, P < 0.006) in comparison with group C. Similar differences were recorded up to the 24th postoperative hour, leading to a significant difference in animal survival (88% in group DF versus 17% in group C, P < 0.001). Furthermore, group DF exhibited an attenuated increase of serum malondialdehyde from the baseline (16% versus 74%, P < 0.05) and lower brain malondialdehyde concentrations (3.7 +/- 1.3 versus 5.7 +/- 2.0 microM/mg of protein, P < 0.05) in comparison with controls. In conclusion, deferoxamine delayed the development of intracranial hypertension and improved survival in pigs with ischemic ALF.
authors.affiliation: Second Department of Surgery, Athens University School of Medicine, Aretaieion University Hospital, Athens, Greece. narkado@otenet.gr
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Arkadopoulos
authors.forename: Demetrios
authors.initials: D
authors.lastname: Vlahakos
authors.forename: Georgia
authors.initials: G
authors.lastname: Kostopanagiotou
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Panagopoulos
authors.forename: Eleni
authors.initials: E
authors.lastname: Karvouni
authors.forename: Christina
authors.initials: C
authors.lastname: Routsi
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Kalimeris
authors.forename: Ioanna
authors.initials: I
authors.lastname: Andreadou
authors.forename: Evangelia
authors.initials: E
authors.lastname: Kouskouni
authors.forename: Vassilios
authors.initials: V
authors.lastname: Smyrniotis
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D002496:Central Venous Pressure; D016207:Cytokines / Q000097:blood; D003676:Deferoxamine / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D019586:Intracranial Hypertension / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D008099:Liver / Q000473:pathology; D017114:Liver Failure, Acute / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008315:Malondialdehyde / Q000097:blood; D017262:Siderophores / Q000627:therapeutic use*; D013552:Swine
chemical_list: D016207:Cytokines; D017262:Siderophores; D008315:Malondialdehyde; D003676:Deferoxamine