Thiel, M and Chouker, A and Ohta, A and Jackson, E and Caldwell, C and Smith, P and Lukashev, D and Bittmann, I and Sitkovsky, MV
(2005)
Oxygenation inhibits the physiological tissue-protecting mechanism and thereby exacerbates acute inflammatory lung injury.
PLoS Biology, 3 (6).
1088 - 1100.
ISSN 1544-9173
Abstract
Acute respiratory distress syndrome (ARDS) usually requires symptomatic supportive therapy by intubation and mechanical ventilation with the supplemental use of high oxygen concentrations. Although oxygen therapy represents a life-saving measure, the recent discovery of a critical tissue-protecting mechanism predicts that administration of oxygen to ARDS patients with uncontrolled pulmonary inflammation also may have dangerous side effects. Oxygenation may weaken the local tissue hypoxia-driven and adenosine A2A receptor (A2AR)-mediated anti-inflammatory mechanism and thereby further exacerbate lung injury. Here we report experiments with wild-type and adenosine A2AR-deficient mice that confirm the predicted effects of oxygen. These results also suggest the possibility of iatrogenic exacerbation of acute lung injury upon oxygen administration due to the oxygenation-associated elimination of A2AR-mediated lung tissue-protecting pathway. We show that this potential complication of clinically widely used oxygenation procedures could be completely prevented by intratracheal injection of a selective A2AR agonist to compensate for the oxygenation-related loss of the lung tissue-protecting endogenous adenosine. The identification of a major iatrogenic complication of oxygen therapy in conditions of acute lung inflammation attracts attention to the need for clinical and epidemiological studies of ARDS patients who require oxygen therapy. It is proposed that oxygen therapy in patients with ARDS and other causes of lung inflammation should be combined with anti-inflammatory measures, e.g., with inhalative application of A2AR agonists. The reported observations may also answer the long-standing question as to why the lungs are the most susceptible to inflammatory injury and why lung failure usually precedes multiple organ failure.
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Details
| Item Type: |
Article
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| Status: |
Published |
| Creators/Authors: |
| Creators | Email | Pitt Username | ORCID  |
|---|
| Thiel, M | | | | | Chouker, A | | | | | Ohta, A | | | | | Jackson, E | | | | | Caldwell, C | | | | | Smith, P | | | | | Lukashev, D | | | | | Bittmann, I | | | | | Sitkovsky, MV | | | |
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| Contributors: |
| Contribution | Contributors Name | Email | Pitt Username | ORCID |
|---|
| Editor | Haslett, Chris | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED |
|
| Date: |
1 June 2005 |
| Date Type: |
Publication |
| Journal or Publication Title: |
PLoS Biology |
| Volume: |
3 |
| Number: |
6 |
| Page Range: |
1088 - 1100 |
| DOI or Unique Handle: |
10.1371/journal.pbio.0030174 |
| Refereed: |
Yes |
| ISSN: |
1544-9173 |
| PubMed ID: |
15857155 |
| Date Deposited: |
11 Jul 2012 18:04 |
| Last Modified: |
20 Dec 2018 00:55 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/12829 |
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