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Distant effects of nitric oxide inhalation in lavage‐induced lung injury in anaesthetised pigs
Author(s) -
NILSSON M. C. A.,
HAMBRAEUSJONZON K.,
ALVING K.,
WIKLUND P.,
BERGQUIST M.,
FREDÉN F.
Publication year - 2013
Publication title -
acta anaesthesiologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.738
H-Index - 107
eISSN - 1399-6576
pISSN - 0001-5172
DOI - 10.1111/aas.12030
Subject(s) - medicine , nitric oxide , lung , hypoxic pulmonary vasoconstriction , nitric oxide synthase , inhalation , cyclic guanosine monophosphate , anesthesia , endogeny , vasoconstriction , pharmacology
Background Inhalation of nitric oxide ( INO ) exerts both local and distant effects. INO in healthy pigs causes down‐regulation of endogenous nitric oxide ( NO ) production and vasoconstriction in lung regions not reached by INO , especially in hypoxic regions, which augments hypoxic pulmonary vasoconstriction. In contrast, in pigs with endotoxemia‐induced lung injury, INO causes increased NO production in lung regions not reached by INO . The aim of this study was to investigate whether INO exerts distant effects in surfactant‐depleted lungs. Methods Twelve pigs were anaesthetised, and the left lower lobe ( LLL ) was separately ventilated. Lavage injury was induced in all lung regions, except the LLL . In six pigs, 40 ppm INO was given to the LLL ( INO group), and the effects on endogenous NO production and blood flow in the lavage‐injured lung regions were studied. Six pigs served as a control group. NO concentration in exhaled air ( ENO ), NO synthase ( NOS ) activity and cyclic guanosine monophosphate (c GMP ) in lung tissue, and regional pulmonary blood flow were measured. Results The calcium ( Ca 2+ )‐dependent NOS activity was lower ( P < 0.05) in the lavage‐injured lung regions in the INO group than in the control group. There were no measurable differences between the groups for Ca 2+ ‐independent NOS activity, c GMP , ENO , or regional pulmonary blood flow. Conclusions Regional INO did not increase endogenous NO production in lavage‐injured lung regions not directly reached by INO , but instead down‐regulated the constitutive calcium‐dependent nitric oxide synthase activity, indicating that NO may inhibit its own synthesis.