liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • 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
Gas Exchange in the Normal Lung: Experimental studies on the effects of positive end-expiratory pressure and body position
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.
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: urn:nbn:se:liu:diva-112364DOI: 10.3384/diss.diva-112364ISBN: 978-91-7519-219-2 (print)OAI: oai:DiVA.org:liu-112364DiVA: diva2:765642
Public defence
2014-12-12, Berzeliussalen, Campus US, Linköpings universitet, Linköping, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2014-11-24 Created: 2014-11-24 Last updated: 2014-11-24Bibliographically approved
List of papers
1. Positive end-expiratory pressure affects regional redistribution of ventilation differently in prone and supine sheep
Open this publication in new window or tab >>Positive end-expiratory pressure affects regional redistribution of ventilation differently in prone and supine sheep
Show others...
2004 (English)In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 32, no 10, 2039-2044 p.Article in journal (Refereed) Published
Abstract [en]

Objective: To examine interactions between positive end-expiratory pressure (PEEP) and posture on regional distribution of ventilation and to compare measurements of regional ventilation with two aerosols: a wet fluorescent microsphere aerosol (FMS, median mass aerodynamic diameter 1.1 μm) and a dry 99mTc-labeled carbon particle aerosol (Technegas, TG, median mass aerodynamic diameter ≈0.1 μm). Design: Experimental study. Setting. Academic laboratory. Subjects: Anesthetized and mechanically ventilated sheep (n = 16). Interventions: Four conditions were studied: prone or supine posture with of without 10 cm H2O PEEP. Measurements and Main results: Comparisons of FMS and TG were made in five animals. The median correlation coefficient of the two ventilation tracers was .95 (range, .91-.96). The mean ventilation per unit weight of dry lung for horizontal planes was almost identical whether measured with TG or FMS. The distribution of ventilation was assessed by analyzing deposition of aerosol in about 1,000 lung regions per animal. Distribution of ventilation down the vertical axis was linear in prone (the slope indicated a dorsal-to-ventral three-fold difference in ventilation) but unimodal in supine animals with the mode in the center of the lung. Redistribution of ventilation with 10 PEEP differed between posture, shifting the mode in supine toward dependent lung regions while eliminating the dorsal-to-ventral gradient in prone. The regional heterogeneity in ventilation was greater in supine sheep at both levels of PEEP, and this was due mostly to greater isogravitational heterogeneity in supine than in prone position. Conclusions: The wet fluorescent microsphere aerosol was as reliable as Technegas for high-resolution measurements of regional ventilation. The markedly different effects of 10 PEEP in supine and prone sheep may have important implications for gas exchange both in noninjured and injured lungs.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-24429 (URN)10.1097/01.CCM.0000142395.82277.6F (DOI)6535 (Local ID)6535 (Archive number)6535 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2014-11-24
2. Marked differences between prone and supine sheep in effect of PEEP on perfusion distribution in zone II lung
Open this publication in new window or tab >>Marked differences between prone and supine sheep in effect of PEEP on perfusion distribution in zone II lung
Show others...
2005 (English)In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 99, no 3, 909-914 p.Article in journal (Refereed) Published
Abstract [en]

The classic four-zone model of lung blood flow distribution has been questioned. We asked whether the effect of positive end-expiratory pressure (PEEP) is different between the prone and supine position for lung tissue in the same zonal condition. Anesthetized and mechanically ventilated prone (n = 6) and supine (n = 5) sheep were studied at 0, 10, and 20 cmH2O PEEP. Perfusion was measured with intravenous infusion of radiolabeled 15-μm microspheres. The right lung was dried at total lung capacity and diced into pieces (≈1.5 cm3), keeping track of the spatial location of each piece. Radioactivity per unit weight was determined and normalized to the mean value for each condition and animal. In the supine posture, perfusion to nondependent lung regions decreased with little relative perfusion in nondependent horizontal lung planes at 10 and 20 cmH2O PEEP. In the prone position, the effect of PEEP was markedly different with substantial perfusion remaining in nondependent lung regions and even increasing in these regions with 20 cmH2O PEEP. Vertical blood flow gradients in zone II lung were large in supine, but surprisingly absent in prone, animals. Isogravitational perfusion heterogeneity was smaller in prone than in supine animals at all PEEP levels. Redistribution of pulmonary perfusion by PEEP ventilation in supine was largely as predicted by the zonal model in marked contrast to the findings in prone. The differences between postures in blood flow distribution within zone II strongly indicate that factors in addition to pulmonary arterial, venous, and alveolar pressure play important roles in determining perfusion distribution in the in situ lung. We suggest that regional variation in lung volume through the effect on vascular resistance is one such factor and that chest wall conformation and thoracic contents determine regional lung volume. Copyright © 2005 the American Physiological Society.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-29636 (URN)10.1152/japplphysiol.01388.2004 (DOI)15015 (Local ID)15015 (Archive number)15015 (OAI)
Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2014-11-24
3. Minimal redistribution of regional ventilation-perfusion ratios by 10 and 20 cmH2O positive end-expiratory pressure in prone sheep
Open this publication in new window or tab >>Minimal redistribution of regional ventilation-perfusion ratios by 10 and 20 cmH2O positive end-expiratory pressure in prone sheep
Show others...
2014 (English)Manuscript (preprint) (Other academic)
Abstract [en]

Background

Positive end-expiratory pressure (PEEP) has posture dependent effects on the distributions of ventilation (V) and perfusion (Q). We examined if redistribution of regional ventilation-perfusion ratios (V/Q) by PEEP was identical in prone and supine.

Methods

Mechanically ventilated sheep (n=16) were studied in prone or supine with 0, 10 and 20 cmH2O PEEP. V and Q were measured with a fluorescent microsphere aerosol and an intravenous infusion of microspheres, respectively. The right lung was dried at total lung capacity and diced into approx. 1000 regions tracking the spatial location of each region.

Results

In prone V/Q was close to unity in all horizontal planes with 0 PEEP and remained so with 10 and 20 PEEP. In supine V/Q was imperfect in the most dependent planes with 0 and 10 PEEP. V/Q approached unity in these planes when 20 PEEP was applied, but V/Q in non-dependent planes increased. The slope of the linear relationship between vertical height and V/Q was not different from zero at any PEEP in prone, but was larger than zero with all PEEP levels in supine. Mean V/Q heterogeneity (SDlogV/Q) was lower in prone at all PEEP levels (0 PEEP: 0.22 vs. 0.37,  10 PEEP: 0.21 vs. and 0.32 and 20 PEEP: 0.19 vs. 0.39, P<0.01).

Conclusions

Redistribution of regional V/Q was minimal in prone with PEEP and remained close to ideal in all horizontal planes. The absence of high V/Q with PEEP in prone may be clinically important when recruitment fails in the supine posture.

National Category
Surgery
Identifiers
urn:nbn:se:liu:diva-112360 (URN)
Available from: 2014-11-24 Created: 2014-11-24 Last updated: 2014-11-24Bibliographically approved
4. Inhibition of constitutive nitric oxide synthase does not influence ventilation: matching in normal prone adult sheep with mechanical ventilation
Open this publication in new window or tab >>Inhibition of constitutive nitric oxide synthase does not influence ventilation: matching in normal prone adult sheep with mechanical ventilation
Show others...
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
National Category
Surgery Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:liu:diva-112361 (URN)10.1213/ANE.0000000000001556 (DOI)000388144000020 ()
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

Vid tiden för disputationen förelåg publikationen som manuskript

Available from: 2014-11-24 Created: 2014-11-24 Last updated: 2017-12-05Bibliographically approved

Open Access in DiVA

Gas Exchange in the Normal Lung: Experimental studies on the effects of positive end-expiratory pressure and body position(2225 kB)2059 downloads
File information
File name FULLTEXT01.pdfFile size 2225 kBChecksum SHA-512
9df208354d2db116bf03ec7525a73e094abfad863238c6b5784bec390d2f192f11813570b2f7786aa979a8e961bd15c1bccb692b18eab86a392cc72cc7b7b84d
Type fulltextMimetype application/pdf
omslag(50 kB)10 downloads
File information
File name COVER01.pdfFile size 50 kBChecksum SHA-512
c9dbffbc855716024cc7719697e16a93a5531df158997b179b40690b08d05484bd9ddcaefd351e099aae8b6b659e22049ccd8536c88edd8ccff34acc1615cd43
Type coverMimetype application/pdf

Other links

Publisher's full text

Authority records BETA

Johansson, Mats J.

Search in DiVA

By author/editor
Johansson, Mats J.
By organisation
Division of Cardiovascular MedicineFaculty of Health SciencesDepartment of Thoracic and Vascular Surgery
Anesthesiology and Intensive Care

Search outside of DiVA

GoogleGoogle Scholar
Total: 2059 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
isbn
urn-nbn

Altmetric score

doi
isbn
urn-nbn
Total: 805 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • 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