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Distant effects of nitric oxide inhalation in lavage induced lung injury in anaesthetised pigs
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
Karolinska universitetssjukhus.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
Karolinska universitetssjukhus.
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2013 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 57, no 3, 326-333 p.Article in journal (Refereed) Published
Abstract [en]

Background Inhalation of nitric oxide (INO) exerts both local and distanteffects. 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 ofthis 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 theeffects on endogenous NO production and blood flow in the lavage-injured lungregions were studied. Six pigs served as a control group. NO concentration inexhaled air (ENO), NO synthase (NOS) activity and cyclic guanosine monophosphate (cGMP) in lung tissue, and regional pulmonary blood flow were measured. Results The calcium (Ca2+)-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 Ca2+-independent NOS activity, cGMP, 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.

Place, publisher, year, edition, pages
2013. Vol. 57, no 3, 326-333 p.
Keyword [en]
Nitric oxide, Nitric oxide synthase, Lavage induced lung injury, pulmonary blood flow, exhaled nitric oxide, cyclic guanosine monophosphate
National Category
Anesthesiology and Intensive Care
Research subject
Anaesthesiology and Intensive Care
Identifiers
URN: urn:nbn:se:uu:diva-157085DOI: 10.1111/aas.12030ISI: 000314652400009OAI: oai:DiVA.org:uu-157085DiVA: diva2:434612
Available from: 2011-08-15 Created: 2011-08-15 Last updated: 2017-12-08Bibliographically approved
In thesis
1. Endogenous Nitric Oxide Production and Pulmonary Blood Flow: during different experimental lung conditions
Open this publication in new window or tab >>Endogenous Nitric Oxide Production and Pulmonary Blood Flow: during different experimental lung conditions
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Nitric oxide (NO) is an important regulator of pulmonary blood flow and attenuates hypoxic pulmonary vasoconstriction (HPV). Nitric oxide is synthesized enzymatically in a number of tissues, including the lungs, and can also be generated from reduction of nitrite during hypoxia and acidosis. Inhaled nitric oxide (INO) is a selective pulmonary vasodilator, with no effects on systemic arterial blood pressure due to inactivation by hemoglobin in the blood. INO has distant effects both within the lungs and in other organs, since NO can be transported to remote tissues bound to proteins, or as more stable molecules of nitrite and nitrate. In healthy pigs, INO causes vasoconstriction and down regulation of endogenous NO production in lung regions not reached by INO, and predominantly so in hypoxic lung regions, i.e. augmentation of HPV. In this thesis, distant effects of INO in pigs with endotoxemic- and lavage-induced lung injuries were studied. INO increased the NO production in lung regions not reached by INO in endotoxemic pigs, whereas endogenous NO production was unaffected in pigs with lavage-induced injury.

Metabolic and/or hypercapnic acidosis frequently occurs in critically ill patients, but whether acidosis affects the endogenous pulmonary NO production is unclear. The regional NO production and blood flow in hyperoxic and hypoxic lung regions, were studied during metabolic and hypercapnic acidosis. Neither metabolic, nor hypercapnic acidosis changed the endogenous NO production in hyperoxic or hypoxic lung regions. Metabolic acidosis potentiated HPV, whereas hypercapnic acidosis transiently attenuated HPV.

In conclusion, the present thesis has demonstrated that INO in experimental sepsis increases the endogenous NO production in lung regions not reached by INO, which may cause increased shunt and poor response to INO. This distant effect is not seen in lavage injuried lungs, an experimental model with less inflammation. Acidosis does not affect the endogenous pulmonary NO production in hyperoxic or hypoxic lung regions. Whereas metabolic acidosis potentiates HPV, hypercapnic acidosis transiently attenuates HPV, due to a combination of hypercapnia-induced increase in cardiac output and a probable vasodilating effect of the CO2-molecule.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2011. 55 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 694
Keyword
Nitric oxide, pulmonary blood flow, endotoxin, nitric oxide inhalation, endothelin, hypercapnia, acidosis, lavage-induced lung injury
National Category
Anesthesiology and Intensive Care
Research subject
Anaesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-157162 (URN)978-91-554-8132-2 (ISBN)
Public defence
2011-09-30, Hedstrandsalen, Akademiska sjukhuset,ing 70, Uppsala, 13:00 (Swedish)
Opponent
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Available from: 2011-09-09 Created: 2011-08-18 Last updated: 2011-11-03Bibliographically approved

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Nilsson, ManjaAlving, KjellBergquist, MariaFredén, Filip

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