PO2 oscillations induce lung injury and inflammation
Abstract Background Mechanical ventilation can lead to ventilator-induced lung injury (VILI). In addition to the well-known mechanical forces of volutrauma, barotrauma, and atelectrauma, non-mechanical mechanisms have recently been discussed as contributing to the pathogenesis of VILI. One such mech...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-03-01
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| Series: | Critical Care |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13054-019-2401-1 |
| _version_ | 1811198682848034816 |
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| author | Stefan Boehme Erik K. Hartmann Thomas Tripp Serge C. Thal Matthias David Dietmar Abraham James E. Baumgardner Klaus Markstaller Klaus U. Klein |
| author_facet | Stefan Boehme Erik K. Hartmann Thomas Tripp Serge C. Thal Matthias David Dietmar Abraham James E. Baumgardner Klaus Markstaller Klaus U. Klein |
| author_sort | Stefan Boehme |
| collection | DOAJ |
| description | Abstract Background Mechanical ventilation can lead to ventilator-induced lung injury (VILI). In addition to the well-known mechanical forces of volutrauma, barotrauma, and atelectrauma, non-mechanical mechanisms have recently been discussed as contributing to the pathogenesis of VILI. One such mechanism is oscillations in partial pressure of oxygen (PO2) which originate in lung tissue in the presence of within-breath recruitment and derecruitment of alveoli. The purpose of this study was to investigate this mechanism’s possible independent effects on lung tissue and inflammation in a porcine model. Methods To separately study the impact of PO2 oscillations on the lungs, an in vivo model was set up that allowed for generating mixed-venous PO2 oscillations by the use of veno-venous extracorporeal membrane oxygenation (vvECMO) in a state of minimal mechanical stress. While applying the identical minimal-invasive ventilator settings, 16 healthy female piglets (weight 50 ± 4 kg) were either exposed for 6 h to a constant mixed-venous hemoglobin saturation (SmvO2) of 65% (which equals a PmvO2 of 41 Torr) (control group), or an oscillating SmvO2 (intervention group) of 40–90% (which equals PmvO2 oscillations of 30–68 Torr)—while systemic normoxia in both groups was maintained. The primary endpoint of histologic lung damage was assessed by ex vivo histologic lung injury scoring (LIS), the secondary endpoint of pulmonary inflammation by qRT-PCR of lung tissue. Cytokine concentration of plasma was carried out by ELISA. A bioinformatic microarray analysis of lung samples was performed to generate hypotheses about underlying pathomechanisms. Results The LIS showed significantly more severe damage of lung tissue after exposure to PO2 oscillations compared to controls (0.53 [0.51; 0.58] vs. 0.27 [0.23; 0.28]; P = 0.0025). Likewise, a higher expression of TNF-α (P = 0.0127), IL-1β (P = 0.0013), IL-6 (P = 0.0007), and iNOS (P = 0.0013) in lung tissue was determined after exposure to PO2 oscillations. Cytokines in plasma showed a similar trend between the groups, however, without significant differences. Results of the microarray analysis suggest that inflammatory (IL-6) and oxidative stress (NO/ROS) signaling pathways are involved in the pathology linked to PO2 oscillations. Conclusions Artificial mixed-venous PO2 oscillations induced lung damage and pulmonary inflammation in healthy animals during lung protective ventilation. These findings suggest that PO2 oscillations represent an independent mechanism of VILI. |
| first_indexed | 2024-04-12T01:35:27Z |
| format | Article |
| id | doaj.art-9b8993bc04b24a36b79c5fde77235844 |
| institution | Directory Open Access Journal |
| issn | 1364-8535 |
| language | English |
| last_indexed | 2024-04-12T01:35:27Z |
| publishDate | 2019-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Critical Care |
| spelling | doaj.art-9b8993bc04b24a36b79c5fde772358442022-12-22T03:53:20ZengBMCCritical Care1364-85352019-03-0123111210.1186/s13054-019-2401-1PO2 oscillations induce lung injury and inflammationStefan Boehme0Erik K. Hartmann1Thomas Tripp2Serge C. Thal3Matthias David4Dietmar Abraham5James E. Baumgardner6Klaus Markstaller7Klaus U. Klein8Department of Anesthesia, General Intensive Care and Pain Management, Medical University of ViennaDepartment of Anesthesiology, Medical Center of the Johannes-Gutenberg University MainzDepartment of Anesthesia, General Intensive Care and Pain Management, Medical University of ViennaDepartment of Anesthesiology, Medical Center of the Johannes-Gutenberg University MainzDepartment of Anesthesiology, Medical Center of the Johannes-Gutenberg University MainzCenter for Anatomy and Cell Biology, Division of Cell and Developmental Biology, Medical University of ViennaDepartment of Anesthesiology, University of Pittsburgh Medical CenterDepartment of Anesthesia, General Intensive Care and Pain Management, Medical University of ViennaDepartment of Anesthesia, General Intensive Care and Pain Management, Medical University of ViennaAbstract Background Mechanical ventilation can lead to ventilator-induced lung injury (VILI). In addition to the well-known mechanical forces of volutrauma, barotrauma, and atelectrauma, non-mechanical mechanisms have recently been discussed as contributing to the pathogenesis of VILI. One such mechanism is oscillations in partial pressure of oxygen (PO2) which originate in lung tissue in the presence of within-breath recruitment and derecruitment of alveoli. The purpose of this study was to investigate this mechanism’s possible independent effects on lung tissue and inflammation in a porcine model. Methods To separately study the impact of PO2 oscillations on the lungs, an in vivo model was set up that allowed for generating mixed-venous PO2 oscillations by the use of veno-venous extracorporeal membrane oxygenation (vvECMO) in a state of minimal mechanical stress. While applying the identical minimal-invasive ventilator settings, 16 healthy female piglets (weight 50 ± 4 kg) were either exposed for 6 h to a constant mixed-venous hemoglobin saturation (SmvO2) of 65% (which equals a PmvO2 of 41 Torr) (control group), or an oscillating SmvO2 (intervention group) of 40–90% (which equals PmvO2 oscillations of 30–68 Torr)—while systemic normoxia in both groups was maintained. The primary endpoint of histologic lung damage was assessed by ex vivo histologic lung injury scoring (LIS), the secondary endpoint of pulmonary inflammation by qRT-PCR of lung tissue. Cytokine concentration of plasma was carried out by ELISA. A bioinformatic microarray analysis of lung samples was performed to generate hypotheses about underlying pathomechanisms. Results The LIS showed significantly more severe damage of lung tissue after exposure to PO2 oscillations compared to controls (0.53 [0.51; 0.58] vs. 0.27 [0.23; 0.28]; P = 0.0025). Likewise, a higher expression of TNF-α (P = 0.0127), IL-1β (P = 0.0013), IL-6 (P = 0.0007), and iNOS (P = 0.0013) in lung tissue was determined after exposure to PO2 oscillations. Cytokines in plasma showed a similar trend between the groups, however, without significant differences. Results of the microarray analysis suggest that inflammatory (IL-6) and oxidative stress (NO/ROS) signaling pathways are involved in the pathology linked to PO2 oscillations. Conclusions Artificial mixed-venous PO2 oscillations induced lung damage and pulmonary inflammation in healthy animals during lung protective ventilation. These findings suggest that PO2 oscillations represent an independent mechanism of VILI.http://link.springer.com/article/10.1186/s13054-019-2401-1Cyclic recruitment and derecruitment of atelectasisPO2 oscillationsVentilator-induced lung injuryVeno-venous extracorporeal membrane oxygenationPathomechanismLung injury |
| spellingShingle | Stefan Boehme Erik K. Hartmann Thomas Tripp Serge C. Thal Matthias David Dietmar Abraham James E. Baumgardner Klaus Markstaller Klaus U. Klein PO2 oscillations induce lung injury and inflammation Critical Care Cyclic recruitment and derecruitment of atelectasis PO2 oscillations Ventilator-induced lung injury Veno-venous extracorporeal membrane oxygenation Pathomechanism Lung injury |
| title | PO2 oscillations induce lung injury and inflammation |
| title_full | PO2 oscillations induce lung injury and inflammation |
| title_fullStr | PO2 oscillations induce lung injury and inflammation |
| title_full_unstemmed | PO2 oscillations induce lung injury and inflammation |
| title_short | PO2 oscillations induce lung injury and inflammation |
| title_sort | po2 oscillations induce lung injury and inflammation |
| topic | Cyclic recruitment and derecruitment of atelectasis PO2 oscillations Ventilator-induced lung injury Veno-venous extracorporeal membrane oxygenation Pathomechanism Lung injury |
| url | http://link.springer.com/article/10.1186/s13054-019-2401-1 |
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