PMID- 35173852
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220219
IS  - 1943-8141 (Print)
IS  - 1943-8141 (Electronic)
IS  - 1943-8141 (Linking)
VI  - 14
IP  - 1
DP  - 2022
TI  - Lung-borne systemic inflammation in mechanically ventilated infant rats due to 
      high PEEP, oxygen, and hypocapnia.
PG  - 343-354
AB  - 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 ~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.
CI  - AJTR Copyright (c) 2022.
FAU - Baumann, Philipp
AU  - Baumann P
AD  - Department of Intensive Care Medicine and Neonatology, University Children's 
      Hospital Zurich Zurich, Switzerland.
AD  - Children's Research Center, University Children's Hospital Zurich Zurich, 
      Switzerland.
FAU - Greco, Francesco
AU  - Greco F
AD  - Department of Intensive Care Medicine and Neonatology, University Children's 
      Hospital Zurich Zurich, Switzerland.
AD  - Children's Research Center, University Children's Hospital Zurich Zurich, 
      Switzerland.
AD  - Zurich Center for Integrative Human Physiology (ZIHP), University Zurich Zurich, 
      Switzerland.
FAU - L'Abate, Pietro
AU  - L'Abate P
AD  - Department of Intensive Care Medicine and Neonatology, University Children's 
      Hospital Zurich Zurich, Switzerland.
AD  - Children's Research Center, University Children's Hospital Zurich Zurich, 
      Switzerland.
FAU - Wellmann, Sven
AU  - Wellmann S
AD  - Zurich Center for Integrative Human Physiology (ZIHP), University Zurich Zurich, 
      Switzerland.
AD  - Division of Neonatology, University of Basel Children's Hospital (UKBB) Basel, 
      Switzerland.
AD  - Department of Neonatology, University Children's Hospital Regensburg (KUNO), 
      University of Regensburg Regensburg, Germany.
FAU - Wiegert, Susanne
AU  - Wiegert S
AD  - Department of Intensive Care Medicine and Neonatology, University Children's 
      Hospital Zurich Zurich, Switzerland.
AD  - Children's Research Center, University Children's Hospital Zurich Zurich, 
      Switzerland.
AD  - Zurich Center for Integrative Human Physiology (ZIHP), University Zurich Zurich, 
      Switzerland.
FAU - Cannizzaro, Vincenzo
AU  - Cannizzaro V
AD  - Department of Intensive Care Medicine and Neonatology, University Children's 
      Hospital Zurich Zurich, Switzerland.
AD  - Children's Research Center, University Children's Hospital Zurich Zurich, 
      Switzerland.
AD  - Zurich Center for Integrative Human Physiology (ZIHP), University Zurich Zurich, 
      Switzerland.
AD  - Department of Neonatology, University Hospital Zurich, University of Zurich 
      Zurich, Switzerland.
LA  - eng
PT  - Journal Article
DEP - 20220115
PL  - United States
TA  - Am J Transl Res
JT  - American journal of translational research
JID - 101493030
PMC - PMC8829610
OTO - NOTNLM
OT  - Interleukin-6
OT  - hyperoxia
OT  - hypocapnia
OT  - positive end-expiratory pressure
OT  - tissue plasminogen activator inhibitor type-1
OT  - tumor necrosis factor-alpha
COIS- None.
EDAT- 2022/02/18 06:00
MHDA- 2022/02/18 06:01
PMCR- 2022/01/15
CRDT- 2022/02/17 05:35
PHST- 2021/03/28 00:00 [received]
PHST- 2021/11/09 00:00 [accepted]
PHST- 2022/02/17 05:35 [entrez]
PHST- 2022/02/18 06:00 [pubmed]
PHST- 2022/02/18 06:01 [medline]
PHST- 2022/01/15 00:00 [pmc-release]
PST - epublish
SO  - Am J Transl Res. 2022 Jan 15;14(1):343-354. eCollection 2022.