Iron chelation attenuates intracranial pressure and improves survival in a swine model of acute liver failure.
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.
Arkadopoulos
Nikolaos
N
Second Department of Surgery, Athens University School of Medicine, Aretaieion University Hospital, Athens, Greece. narkado@otenet.gr
Vlahakos
Demetrios
D
Kostopanagiotou
Georgia
G
Panagopoulos
Dimitrios
D
Karvouni
Eleni
E
Routsi
Christina
C
Kalimeris
Konstantinos
K
Andreadou
Ioanna
I
Kouskouni
Evangelia
E
Smyrniotis
Vassilios
V
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
D016207:Cytokines; D017262:Siderophores; D008315:Malondialdehyde; D003676:Deferoxamine