Partial liquid ventilation with perflubron attenuates in vivo oxidative damage to proteins and lipids

Alexandre T. Rotta, Björn Gunnarsson, Lynn J. Hernan, Bradley P. Fuhrman, David M. Steinhorn

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Objective: To determine the impact of partial liquid ventilation on the degree of pulmonary damage by reactive oxygen species in a model of acute lung injury caused by systemic endotoxemia. Design: A prospective, controlled, in vivo, animal laboratory study. Setting: Animal research facility of a health sciences university. Subjects: Forty New Zealand White rabbits. Interventions: Mature rabbits were anesthetized and instrumented with a tracheostomy and vascular catheters. Animals were assigned to receive either partial liquid ventilation (n = 16) with perflubron (18 mL/kg via endotracheal tube) or conventional mechanical ventilation (n = 16). Both groups were ventilated using similar strategies, with an FIO2 of 1.0 and tidal volume as required to obtain a normal PaCO2. Animals were then given 0.9 mg/kg Escherichia coli endotoxin intravenously over 30 mins. Eight uninjured instrumented and mechanically ventilated animals served as controls. Partial liquid ventilation or conventional ventilation was continued for 4 hrs before the animals were killed. Lung homogenates were analyzed for malondialdehyde (MDA) and 4-hydroxy-2(E)-nonenal (4-HNE) concentrations using a colorimetric assay. To assess protein oxidative damage, carbonyl groups in protein side chains were derivatized with 2,4- dinitrophenylhydrazine followed by Western blotting with a dinitrophenylated- specific primary antibody. Measurements and Main Results: MDA (713.42 ± 662 vs. 1601.4 ± 1156 nmol/g protein; p = .023) and MDA plus 4-HNE (1480.24 ± 788 vs. 2675.2 ± 1628 nmol/g protein; p = .038) concentrations were lower in animals treated with partial liquid ventilation compared with conventionally ventilated animals, respectively. Animals treated with partial liquid ventilation exhibited attenuation of dinitrophenylated-derivatized protein bands by Western blotting, indicating a reduction in protein oxidative damage. The presence of perfluorocarbon did not interfere with the MDA assay when assessed by independent analysis in vitro. Perflubron did not serve as a sink for peroxyl radicals produced in the aqueous phase during separate in vitro oxidation experiments. Conclusions: Partial liquid ventilation attenuates oxidative damage to lipids and proteins during experimental acute lung injury. This finding is not caused by binding of lipid peroxidation products to perflubron or by the peroxyl radical scavenging properties of perflubron.

Original languageEnglish (US)
Pages (from-to)202-208
Number of pages7
JournalCritical Care Medicine
Volume28
Issue number1
StatePublished - 2000
Externally publishedYes

Keywords

  • Acute respiratory distress syndrome
  • Endotoxin
  • Fluorocarbons
  • Inflammation
  • Liquid ventilation
  • Lung disease
  • Malondialdehyde
  • Oxidative damage
  • Respiratory failure

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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    Rotta, A. T., Gunnarsson, B., Hernan, L. J., Fuhrman, B. P., & Steinhorn, D. M. (2000). Partial liquid ventilation with perflubron attenuates in vivo oxidative damage to proteins and lipids. Critical Care Medicine, 28(1), 202-208.