uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Distant effects of nitric oxide inhalation in endotoxemic pigs
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
Show others and affiliations
2010 (English)In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 38, no 1, 242-248 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Inhalation of nitric oxide (INO) has distant effects. By a blood- borne factor, INO down-regulates endogenous nitric oxide production in healthy pig lungs, resulting in vasoconstriction in lung regions not directly reached by INO. The aim of this study was to investigate whether INO has distant effects in endotoxemic pig lungs. The hypothesis was that INO down-regulates endogenous NO production in lung regions not reached by INO. DESIGN: Prospective, randomized animal study. SETTING: University hospital research laboratory. SUBJECTS: Twenty-two pairs of domestic pigs. INTERVENTIONS: Cross-circulation was established in 22 pairs of anesthetized pigs. Nine pairs received endotoxin (control group) and 13 pairs received endotoxin, with one pig inhaling NO (80 ppm) and one pig receiving blood from that pig (NO-blood recipient group). MEASUREMENTS AND MAIN RESULTS: NO in exhaled air, NO synthase activity in lung tissue, endothelin-1 in the blood, ETA and ETB receptor immunoreactivity in lung tissue, vital parameters, and blood gases were measured. Endotoxin per se increased NO in exhaled air by 100% compared to baseline (control group). In the NO-blood recipient group, i.e., pigs receiving blood from the NO-inhaling pigs, NO in exhaled air increased by 300% (p = .03). The Ca-dependent NO synthase activity was higher in these pigs (p = .02), indicating increased endogenous NO production. The ET B receptor immunoreactivity was higher in the NO-blood recipient group (p = .004). CONCLUSIONS: As opposed to findings in healthy pigs, INO in endotoxemic pigs causes an increase in endogenous NO production in lung regions not reached by INO. Increased NO production in nonventilated lung regions may cause vasodilatation, counteracting the INO-induced increase in blood flow to the ventilated lung regions.

Place, publisher, year, edition, pages
2010. Vol. 38, no 1, 242-248 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-113072DOI: 10.1097/CCM.0b013e3181b4a4fcISI: 000273224800033PubMedID: 19730256OAI: oai:DiVA.org:uu-113072DiVA: diva2:289531
Available from: 2010-01-25 Created: 2010-01-25 Last updated: 2017-12-12Bibliographically 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
Supervisors
Available from: 2011-09-09 Created: 2011-08-18 Last updated: 2011-11-03Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed
By organisation
Anaesthesiology and Intensive CareDepartment of Medical Sciences
In the same journal
Critical Care Medicine
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 411 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf