Baumann, Philipp and Greco, Francesco and L'Abate, Pietro and Wellmann, Sven and Wiegert, Susanne and Cannizzaro, Vincenzo (2022) Lung-borne systemic inflammation in mechanically ventilated infant rats due to high PEEP, oxygen, and hypocapnia. AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH, 14 (1). pp. 343-354. ISSN 1943-8141,
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Background: Intensive care practice calls for ventilator adjustments due to fast-changing clinical conditions in ventilated critically ill children. These adaptations include positive end-expiratory pressure (PEEP), fraction of inspired oxygen (FiO(2)), and respiratory rate (RR). It is unclear which alterations in ventilator settings trigger a significant systemic inflammatory response. Methods: Fourteen-day old Wistar rat pups were randomized to the following groups: (a) "control" with tidal volume similar to 8 mL/kg, PEEP 5 cmH(2)O, FiO(2) 0.4, RR 90 min(-1), (b) "PEEP 1", (c) "PEEP 9" (d) "FiO(2) 0.21", (e) "FiO(2) 1.0", (f) "hypocapnia" with RR of 180 min(-1), and (g) "hypercapnia" with RR of 60 min(-1). Following 120 min of mechanical ventilation, plasma for inflammatory biomarker analyses was obtained by direct cardiac puncture at the end of the experiment. Results: Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were driven by FiO(2) 0.4 and 1.0 (P=0.02, P<0.01, respectively), tissue plasminogen activator inhibitor type-1 (tPAI-1) was increased by high PEEP (9 cmH(2)O, P<0.05) and hypocapnia (P<0.05), and TNF-alpha was significantly lower in hypercapnia (P<0.01). Tissue inhibitor of metalloproteinase-1 (TIMP-1), cytokine-induced neutrophil chemoattractant 1 (CINC-1), connective tissue growth factor (CTGF), and monocyte chemoattractant protein-1 (MCP-1) remained unaffected. Conclusion: Alterations of PEEP, FiO(2), and respiratory frequency induced a significant systemic inflammatory response in plasma of infant rats. These findings underscore the importance of lung-protective ventilation strategies. However, future studies are needed to clarify whether ventilation induced systemic inflammation in animal models is pathophysiologically relevant to human infants.
Item Type: | Article |
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Uncontrolled Keywords: | RESPIRATORY-DISTRESS-SYNDROME; TIDAL VOLUME VENTILATION; END-EXPIRATORY PRESSURE; INTENSIVE-CARE; BLOOD-VOLUME; INJURY; CHILDREN; EPIDEMIOLOGY; MULTICENTER; SUPPORT; Interleukin-6; tumor necrosis factor-alpha; tissue plasminogen activator inhibitor type-1; hyperoxia; positive end-expiratory pressure; hypocapnia |
Subjects: | 600 Technology > 610 Medical sciences Medicine |
Divisions: | Medicine > Lehrstuhl für Kinder- und Jugendmedizin |
Depositing User: | Dr. Gernot Deinzer |
Date Deposited: | 27 Feb 2024 10:15 |
Last Modified: | 27 Feb 2024 10:15 |
URI: | https://pred.uni-regensburg.de/id/eprint/57922 |
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