Influence of tidal volume on pulmonary NO release, tissue lipid peroxidation and surfactant phospholipids

Hammerschmidt, Stefan; Schiller, Jürgen; Kühn, Hartmut; Meybaum, Michael; Geßner, Christian; Sandvoß, Torsten; Arnold, Klaus; Wirtz, Hubert

doi:10.1016/s0925-4439(03)00126-1

Cited by 27 publications

(13 citation statements)

References 38 publications

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“…HV T ventilation is associated with increased levels of NO metabolites in BALF (15,17). In our study, BALF concentrations of NO metabolites were increased in WT but not in NOS3 Ϫ/Ϫ mice subjected to HV T ventilation.…”

Section: Discussionsupporting

confidence: 40%

Nitric oxide synthase 3 contributes to ventilator-induced lung injury

Vaporidi

Francis

Bloch

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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Vaporidi K, Francis RC, Bloch KD, Zapol WM. Nitric oxide synthase 3 contributes to ventilator-induced lung injury. Am J Physiol Lung Cell Mol Physiol 299: L150-L159, 2010. First published May 7, 2010 doi:10.1152/ajplung.00341.2009.-Nitric oxide synthase (NOS) depletion or inhibition reduces ventilator-induced lung injury (VILI), but the responsible mechanisms remain incompletely defined. The aim of this study was to elucidate the role of endothelial NOS, NOS3, in the pathogenesis of VILI in an in vivo mouse model. Wild-type and NOS3-deficient mice were ventilated with high-tidal volume (HVT; 40 ml/kg) for 4 h, with and without adding NO to the inhaled gas. Additional wild-type mice were pretreated with tetrahydrobiopterin and ascorbic acid, agents that can prevent NOS-generated superoxide production. Arterial blood gas tensions, histology, and lung mechanics were evaluated after 4 h of HVT ventilation. The concentration of protein, IgM, cytokines, malondialdehyde, and 8-isoprostane were measured in bronchoalveolar lavage fluid (BALF). Myeloperoxidase activity, total and oxidized glutathione levels, and NOS-derived superoxide production were measured in lung tissue homogenates. HVT ventilation induced VILI in wild-type mice, as reflected by decreased lung compliance, increased concentrations of protein and cytokines in BALF, and oxidative stress. All indices of VILI were ameliorated in NOS3-deficient mice. Augmenting pulmonary NO levels by breathing NO during mechanical ventilation did not increase lung injury in NOS3-deficient mice. HVT ventilation increased NOS-inhibitable superoxide production in lung extracts from wild-type mice but not in those from NOS3-deficient mice. Administration of tetrahydrobiopterin and ascorbic acid ameliorated VILI in wild-type mice. Our results indicate that NOS3 contributes to ventilator-induced lung injury via increased production of superoxide.superoxide; pulmonary edema; inflammation MECHANICAL VENTILATION with high-tidal volumes (HV T ) may initiate and/or exacerbate acute lung injury (ALI) via a process known as ventilator-induced lung injury (VILI) (14,29). Shear forces generated during HV T ventilation induce alveolar-capillary barrier disruption and pulmonary inflammation. Several mechanisms have been implicated in the development of VILI, including neutrophil infiltration, as well as increased production of proinflammatory cytokines, reactive oxygen species (ROS), and nitric oxide (NO) (14,29,33).NO is produced by three NO synthase (NOS) isoforms: neuronal, inducible, and endothelial NOS (NOS 1, 2, and 3, respectively) (12). Several studies have shown that NOS2 contributes to VILI (15,25,30), whereas the role of NOS3 remains controversial. Transgenic mice overexpressing NOS3 (38) and mice that were congenitally NOS3 deficient (36) were both found to be protected from VILI.NOS3 couples L-arginine oxidation and O 2 reduction leading to the production of NO. Under certain conditions, such as substrate (L-arginine) or cofactor (e.g., tetrahydrobiopterin, BH 4 ) depletion, ...

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Section: Discussionsupporting

confidence: 40%

Nitric oxide synthase 3 contributes to ventilator-induced lung injury

Vaporidi

Francis

Bloch

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Therefore, we suggest to use MALDI-TOF MS for the evaluation of the fatty acid composition of BAL and, for instance, 31 P NMR for quantitative PL analysis. First aspects of this approach were already successfully used in BAL analysis [21].…”

Section: Resultsmentioning

confidence: 99%

Analysis of the phospholipid composition of bronchoalveolar lavage (BAL) fluid from man and minipig by MALDI-TOF mass spectrometry in combination with TLC

Sommerer

Süß

Hammerschmidt³

et al. 2004

Journal of Pharmaceutical and Biomedical Analysis

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“…For example, EBC nitrite significantly increases in healthy recreational runners in a time-dependent manner without change in lipid peroxidation 54 , suggesting an increased nitric oxide production independent of significant lung injury. Nitrite level increases with lung distention in the EBC of COPD or ventilated patients with or without ARDS 6,26 as well as with high V T ventilation of isolated rabbit lungs 55 . EBC nitrate reflects the severity of asthma better than nitrite or exhaled nitric oxide 56 .…”

Section: Discussionmentioning

confidence: 99%