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No effect of metabolic acidosis on nitric oxide production in hypoxic and hyperoxic lung regions in 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 Surgical Sciences, Anaesthesiology and Intensive Care.
2011 (English)In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 202, no 1, 59-68 p.Article in journal (Refereed) Published
Abstract [en]

Aim: In the severely ill intensive care patients metabolic acidosis and hypoxia often co-exist. We studied the effects of metabolic acidosis on nitric oxide synthase (NOS) dependent and NOS independent nitric oxide (NO) production in hypoxic and hyperoxic lung (HL) regions in a pig model. Methods: Eighteen healthy anaesthetized pigs were separately ventilated with hypoxic gas to the left lower lobe (LLL) and hyperoxic gas to the rest of the lung. Six pigs received HCl infusion (HCl group), six pigs received the non-specific NOS inhibitor N omega-nitro-l-arginine methyl ester (l-NAME) and HCl infusions (l-NAME + HCl group) and six pigs received buffered Ringer's solution (control group). NO concentration in exhaled air (ENO), NOS activity in lung tissue, and regional pulmonary blood flow were measured. Results: Metabolic acidosis, induced by infusion of HCl, decreased the relative perfusion to the hypoxic LLL from 7 (3) [mean (SD)] to 3 (1) % in the HCl group (P < 0.01), and from 4 (1) to 1 (1) % in the l-NAME + HCl group (P < 0.05), without any measurable significant changes in ENO from hypoxic or HL regions There were no significant differences between the HCl and control groups for Ca2+-dependent (cNOS) or Ca2+-independent NOS (iNOS) activity in hypoxic or HL regions. Conclusions: Metabolic acidosis augmented the hypoxic pulmonary vasoconstriction, without any changes in pulmonary NOS dependent or NOS independent NO production. When acidosis was induced during ongoing NOS blockade, the perfusion of hypoxic lung regions was almost abolished, indicating acidosis-induced pulmonary vasoconstriction was not NO dependent.

Place, publisher, year, edition, pages
2011. Vol. 202, no 1, 59-68 p.
Keyword [en]
acidosis, exhaled nitric oxide, hypoxic pulmonary vasoconstriction, nitric oxide, nitric oxide synthase blockade
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-152868DOI: 10.1111/j.1748-1716.2011.02250.xISI: 000289250500007PubMedID: 21251235OAI: oai:DiVA.org:uu-152868DiVA: diva2:414150
Available from: 2011-05-02 Created: 2011-05-02 Last updated: 2017-12-11Bibliographically 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

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