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Inducible nitric oxide mediates systemic microvascular leak following acid aspiration and mechanical ventilation

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Authors
Choi, Won-Il; Quinn, Deborah A.; Kwon, Kun Young; Park, Kwon Moo; Seo, Jeong Wook; Syrkina, Olga; Ochoa, Cristhiaan D.; Bonventre, Joseph V.; Hales, Charles A.
Issue Date
2008
Publisher
Wiley-Blackwell
Citation
Bas Appl Pathol 2008; 1: 23-29
Keywords
Adult respiratory distress syndrome; nitric oxide synthase; artificial respiration; hydrochloric acid; l-NIL; rat
Abstract
Background and aims: The systemic effects associated with mechanical ventilation of lungs injured by hydrochloric acid (HCl) aspiration are unexplored. We hypothesize that low dose acid aspiration will predispose the lung and the kidney to damage from large tidal volumes through activation of inducible nitric oxide synthase (iNOS). Materials and methods: Hydrochloric acid (HCl; pH 1.25, 1 mL/kg), or an equal amount of 0.9% sodium chloride (NaCl), were inserted into the trachea of rats immediately prior to mechanical ventilation. Rats were then ventilated with room air at 85 breaths per minute for 2 hours, either with a tidal volume (VT) of 7 mL/kg or 14 mL/kg (VT7, VT14) and zero end expiratory pressure. Kidney microvascular leak, which was assessed by measuring urine protein over 24 hours and by Evans blue dye (EBD) technique, was used as an indicator of systemic microvascular leak. Results: A significant microvascular leak occurred in both lung and kidney exposed to VT14 with HCl compared to those exposed to either VT7 with HCl or the NaCl control group. iNOS activity was significantly increased in the lung and the kidney tissue in VT14 with acid aspiration. The relatively selective iNOS inhibitor, l-N6-(1-iminoethyl)lysine (l-NIL), attenuated the EBD microvascular leak in lung and kidney and the proteinuria in the VT14 with acid aspiration group. Conclusion: iNOS may have mediated the systemic microvascular leak in the present model.
ISSN
1755-9294
Language
English
URI
http://hdl.handle.net/10371/3695
DOI
https://doi.org/10.1111/j.1755-9294.2008.00005.x
https://doi.org/10.1111/j.1755-9294.2008.00005.x
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College of Medicine/School of Medicine (의과대학/대학원)Pathology (병리학전공)Journal Papers (저널논문_병리학전공)
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