Partial liquid ventilation (FLV) attenuates oxidative damage to the lung in a model of acute lung injury (AU)
Introd-ctioa: Several experimental models of AU treated with PLV exhibit attenuation in tissue damage and inflammation. We have previously demonstrated a reduction in pulmonary leukostasis during PLV1 and a decrease in free radical release by alveolar macrophages exposed to perfluorocarbons:. In view of the central role played by activated leukocytes in cellular ondatrvt damage and ALL we hypothesized that PLV would also reduce lung injury induced by reactive oxygen species. Methods: Thirty-one NZW rabbits were anesthetized and instrumented with a uacheostomy and vascular catheters. Twenty-eight animals were randomly assigned to receive either PLV with perflubron (ISml/kg via ETT, LiquiVent, Alliance Pharmaceutical Corp.) or conventional ventilation (CV) and were ventilated with FiOi=l and Ve required to obtain normal pCOj. Thirty minutes after onset of ventilation, animals were given 0.9 mg/kg of £co// LPS, IV. PLV or CV was continued for 4 hours before sacrifice. Three uninjured animals served as normal controls. Lungs were frozen at -70°C. Lung samples were homogenized in buffer solutions and clarified. Malooaldchyde (MDA) and 4-bydroxy-2(E)-nonenal (4-HNE) concentrations, by-products of lipid peroridation, were measured by a cotoimethc assay. To assess protein oxidative damage, 2,4-dinitrophenylhydrazine (DNPH) derivatized samples underwent SDSPAGE separation followed by Western blotting with a DNP-pecific primary antibody. Results; (mean+SD) MDA (uaoi/g proton) MDA+ 4-HNE (umol/g protein) CV (n=14) 8.01+5.78 13.37 + 8.14 PLV (n°14) 3.57±3.31 (pO.02) 7.40 + 3.94 (p<0.05) Control (n=3) 2.75 ±0.65 3.66+1.91 Western blotting demonstrated an attenuation of DNP-derivatized bands of carbonyt groups in lung tissue of PLV treated animals when compared to CV treated animals. CoachisioBs: PLV attenuates oxidatrve damage to proteins and lipids in a model of ALL We speculate that these findings are related to decreased pulmonary loikost-w and reduced free radical generation by leukocytes during PLV.
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