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Pulmonary effects of desferrioxamine in the treatment of an experimental model of fulminant hepatic failure
Critical Care volume 11, Article number: P399 (2007)
Desferrioxamine (DFX) is a clinically approved iron chelator used to treat iron overload. It has also shown beneficial effects in experimental acute liver failure (ALF) by inhibiting oxidative damage . Lung dysfunction commonly complicates ALF. Iron-mediated processes have been shown to contribute to it . We hypothesized that inhibition of oxidative reactions by means of iron chelation could attenuate lung injury after ischemic ALF.
In 14 domestic pigs fulminant hepatic failure was induced by surgical devascularization of the liver, and animals were monitored postoperatively for 24 hours under general anaesthesia. Seven randomly assigned pigs (DFX group) were treated with intravenous desferrioxamine (14.5 mg/kg/hour for 6 hours and 2.4 mg/kg/hour for the next 18 hours), whereas the remaining (control group) received standard care. Bronchoalveolar lavage fluid (BALF) was obtained after central line placement, after surgery, at 7 hours, and 24 hours postoperatively and was analysed for cell counts, biochemical and oxidative markers of lung injury.
DFX resulted in maintenance of blood pressure (mmHg) (84 ± 27 in DFX vs 51 ± 16 in control, P < 0.05) and attenuated the increase of intracranial pressure (mmHg) (19 ± 10 in DFX vs 36 ± 9 in control, P < 0.01) at 24 hours. Protein levels in BALF were increased in controls whereas in the DFX group protein (μg/ml) was significantly lower (at 7 hours 398 ± 219 vs 187 ± 67, respectively, P < 0.01; and at 24 hours 261 ± 112 vs 162 ± 52, respectively, P < 0.05). Nitrites in BALF were elevated at 7 hours in controls whereas a reduction was observed in the DFX group (3.924 ± 3.67 μM vs 0.590 ± 0.69 μM, respectively, P < 0.05). Phospholipase A2, platelet-activating factor acetylhydrolase, nitrates, total cell counts, neutrophils and macrophages in BALF all increased in the control and DFX groups but did not differ significantly between them.
Treatment of ALF with DFX attenuates the increase of protein and nitrites in BALF, but does not seem to significantly affect phospholipase A2, platelet-activating factor acetylhydrolase, nitrates, macrophages or neutrophils. The observed effects may suggest a protective role of DFX on lung inflammation during the first 24 hours of ALF.
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Am J Respir Cell Mol Biol. 2003, 29: 427. 10.1165/rcmb.F278
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Kalimeris, K., Kostopanagiotou, G., Routsi, C. et al. Pulmonary effects of desferrioxamine in the treatment of an experimental model of fulminant hepatic failure. Crit Care 11, P399 (2007). https://0-doi-org.brum.beds.ac.uk/10.1186/cc5559
- Lung Injury
- Iron Overload
- Acute Liver Failure
- Bronchoalveolar Lavage Fluid