Desferrioxamine attenuates minor lung injury following surgical acute liver failure.
Acute liver failure (ALF) can be complicated by lung dysfunction. The aim of this study was to test the hypothesis that inhibition of oxidative stress through iron chelation with desferrioxamine (DFX) attenuates pulmonary injury caused by ALF. 14 adult female domestic pigs were subjected to surgical devascularisation of the liver and were randomised to a study group (DFX group, n = 7), which received post-operative intravenous infusion of DFX (14.5 mg x kg(-1) x h(-1) for the first 6 h post-operatively and 2.4 mg x kg(-1) x h(-1) until completion of 24 h), and a control group (n = 7). Post-operative lung damage was evaluated by histological and bronchoalveolar lavage fluid (BALF) analysis. DFX resulted in reduced BALF protein levels and tissue phospholipase (PL)A(2) activity. Plasma malondialdehyde and BALF nitrate and nitrite concentrations were lower, while catalase activity in the lung was higher after DFX treatment. PLA(2), platelet-activating factor acetylhydrolase and total cell counts in BALF did not differ between groups. Histological examination revealed reduced alveolar collapse, pneumonocyte necrosis and total lung injury in the DFX-treated animals. DFX reduced systemic and pulmonary oxidative stress during ALF. The limited activity of PLA(2) and the attenuation of pneumonocyte necrosis could represent beneficial mechanisms by which DFX improves alveolar-capillary membrane permeability and prevents alveolar space collapse.
Kostopanagiotou
G G
GG
Second Dept of Anaesthesiology, University of Athens School ofMedicine, Attikon Hospital, Athens, Greece. gnakos@cc.uoi.gr
Kalimeris
K A
KA
Arkadopoulos
N P
NP
Pafiti
A
A
Panagopoulos
D
D
Smyrniotis
V
V
Vlahakos
D
D
Routsi
C
C
Lekka
M E
ME
Nakos
G
G
D055371:Acute Lung Injury / Q000188:drug therapy* / Q000209:etiology; D000704:Analysis of Variance; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002374:Catalase / Q000378:metabolism; D003676:Deferoxamine / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D007262:Infusions, Intravenous; D017114:Liver Failure, Acute / Q000150:complications*; D008315:Malondialdehyde / Q000097:blood; D009336:Necrosis; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D054467:Phospholipases A2 / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D011897:Random Allocation; D013552:Swine
D009566:Nitrates; D009573:Nitrites; D011506:Proteins; D008315:Malondialdehyde; D002374:Catalase; D054467:Phospholipases A2; D003676:Deferoxamine