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Inhibition of constitutive nitric oxide synthase does not influence ventilation: matching in normal prone adult sheep with mechanical ventilation
Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
Department of Physiology, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Norway.
Department of Physiology, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Norway.
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2016 (English)In: Anesthesia and Analgesia, ISSN 0003-2999, E-ISSN 1526-7598, Vol. 123, no 6, 1492-1499 p.Article in journal (Refereed) Published
Abstract [en]

Background

Local formation of nitric oxide (NO) in the lung in proportion to ventilation, leading to vasodilation, is a putative mechanism behind ventilation- perfusion matching. We examined the role of local constitutive NO formation on regional distributions of ventilation (V) and perfusion (Q) and ventilation-perfusion matching (V/Q) in mechanically ventilated adult sheep with normal gas exchange.

Methods

V and Q were analyzed in lung regions (≈1.5 cm3) before and after inhibition of constitutive nitric oxide synthase (cNOS) with Nω-nitro-L-arginine methyl ester (L-NAME) (25 mg/kg) in seven prone sheep ventilated with PEEP. V and Q were measured using aerosolized fluorescent and infused radiolabeled microspheres, respectively. The animals were exsanguinated while deeply anaesthetized; lungs were excised, dried at total lung capacity and divided into cube units. The spatial location for each cube was tracked and fluorescence and radioactivity per unit weight determined.

Results

Pulmonary artery pressure increased significantly after L-NAME (from mean 16.6 to 23.6 mmHg, P<0.01) while there were no significant changes in PaO2, PaCO2 or SD log(V/Q). Distribution of V was not influenced by L-NAME but a small redistribution of Q from ventral to dorsal lung regions resulting in less heterogeneity in Q along the gravitational axis was seen (p<0.01). Perfusion to regions with the highest ventilation (5th quintile of the V distribution) remained unchanged with L-NAME.

Conclusions

There was minimal or no influence of cNOS inhibition by L-NAME on the distributions of V and Q, and V/Q in prone anesthetized and ventilated adult sheep with normal gas exchange.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2016. Vol. 123, no 6, 1492-1499 p.
National Category
Surgery Cardiac and Cardiovascular Systems
Identifiers
URN: urn:nbn:se:liu:diva-112361DOI: 10.1213/ANE.0000000000001556ISI: 000388144000020OAI: oai:DiVA.org:liu-112361DiVA: diva2:765625
Note

Funding agencies: Faculty of Medicine and Health Sciences, Linkoping University, Sweden; Faculty of Medicine, University of Oslo, Norway; Anders Jahres Foundation for Promotion of Sciences, Norway; AGA Gas AB, Lidingo, Sweden

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Available from: 2014-11-24 Created: 2014-11-24 Last updated: 2017-12-05Bibliographically approved
In thesis
1. Gas Exchange in the Normal Lung: Experimental studies on the effects of positive end-expiratory pressure and body position
Open this publication in new window or tab >>Gas Exchange in the Normal Lung: Experimental studies on the effects of positive end-expiratory pressure and body position
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

BACKGROUND: The principal function of the lung is gas exchange requiring adequate ventilation and perfusion at the level of the alveoli. The efficiency of gas exchange is depending on the distributions of regional ventilation (V) and pulmonary blood flow (Q) and their correlation.

AIMS: To validate a high-resolution method to quantify regional V and to investigate the combined effect of positive end-expiratory pressure (PEEP) and body position on distributions of regional V and Q in the normal lung with mechanical ventilation. To assess the matching of V and Q by calculating ventilation-perfusion ratio (V/Q) heterogeneity, determining the spatial distribution of V/Q and to investigate the role of nitric oxide (NO) in regional V/Q matching.

METHODS: Anesthetized mechanically ventilated sheep were studied in prone or supine position with different levels of PEEP (0, 10 and 20 cmH2O). Measurements of regional V were done by determining the deposition of a wet aerosol of fluorescent microspheres (FMS) with a median mass aerodynamic diameter of 1.1 μm, and validated against Technegas. Radioactive microspheres, 15 μm in diameter, were used for determining regional Q. Nitric oxide synthase (NOS) was inhibited with Nω-nitro-L-arginine methyl ester (L-NAME) to evaluate the role of NO on regional V/Q matching. The right lung was dried at total lung capacity and diced in approx. 1000 regions tracking the spatial location of each region.

RESULTS: The deposition of FMS mirrored regional deposition of Technegas and thus regional ventilation well. In prone, with PEEP, only a small dorsal redistribution of V but not of Q was observed. The vertical Q gradient was abolished with PEEP in prone position in conflict with the classical zonal model. In supine position both V and Q were distributed with a unimodal gradient and PEEP displaced the mode further dorsally. V/Q heterogeneity was greater in supine than in prone position with and without PEEP. Furthermore, PEEP generated regions with high V/Q in supine but not in prone position. Inhibition of NOS did not change the V/Q distribution in prone position.

CONCLUSION: There were marked differences in redistribution of regional ventilation and regional pulmonary blood flow between prone and supine position when PEEP was applied. NO was not an active mechanism for V/Q matching in normal sheep lungs.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2014. 74 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1425
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:liu:diva-112364 (URN)10.3384/diss.diva-112364 (DOI)978-91-7519-219-2 (ISBN)
Public defence
2014-12-12, Berzeliussalen, Campus US, Linköpings universitet, Linköping, 13:00 (Swedish)
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Available from: 2014-11-24 Created: 2014-11-24 Last updated: 2014-11-24Bibliographically approved

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Johansson, MatsEscobar Kvitting, John-PederWalther, Sten

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Division of Cardiovascular MedicineFaculty of Health SciencesDepartment of Thoracic and Vascular SurgeryDivision of Radiological SciencesCenter for Medical Image Science and Visualization (CMIV)
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Anesthesia and Analgesia
SurgeryCardiac and Cardiovascular Systems

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