PMID- 19901912
OWN - NLM
STAT- MEDLINE
DCOM- 20100202
LR  - 20230216
IS  - 1530-0307 (Electronic)
IS  - 0023-6837 (Print)
IS  - 0023-6837 (Linking)
VI  - 90
IP  - 1
DP  - 2010 Jan
TI  - Plasma concentrations of inflammatory cytokines rise rapidly during ECMO-related 
      SIRS due to the release of preformed stores in the intestine.
PG  - 128-39
LID - 10.1038/labinvest.2009.119 [doi]
AB  - Extracorporeal membrane oxygenation (ECMO) is a life-saving support system used 
      in neonates and young children with severe cardiorespiratory failure. Although 
      ECMO has reduced mortality in these critically ill patients, almost all patients 
      treated with ECMO develop a systemic inflammatory response syndrome (SIRS) 
      characterized by a 'cytokine storm', leukocyte activation, and multisystem organ 
      dysfunction. We used a neonatal porcine model of ECMO to investigate whether 
      rising plasma concentrations of inflammatory cytokines during ECMO reflect de 
      novo synthesis of these mediators in inflamed tissues, and therefore, can be used 
      to assess the severity of ECMO-related SIRS. Previously healthy piglets 
      (3-week-old) were subjected to venoarterial ECMO for up to 8 h. SIRS was assessed 
      by histopathological analysis, measurement of neutrophil activation (flow 
      cytometry), plasma cytokine concentrations (enzyme immunoassays), and tissue 
      expression of inflammatory genes (PCR/western blots). Mast cell degranulation was 
      investigated by measurement of plasma tryptase activity. Porcine neonatal ECMO 
      was associated with systemic inflammatory changes similar to those seen in human 
      neonates. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8) 
      concentrations rose rapidly during the first 2 h of ECMO, faster than the tissue 
      expression of these cytokines. ECMO was associated with increased plasma mast 
      cell tryptase activity, indicating that increased plasma concentrations of 
      inflammatory cytokines during ECMO may result from mast cell degranulation and 
      associated release of preformed cytokines stored in mast cells. TNF-alpha and 
      IL-8 concentrations rose faster in plasma than in the peripheral tissues during 
      ECMO, indicating that rising plasma levels of these cytokines immediately after 
      the initiation of ECMO may not reflect increasing tissue synthesis of these 
      cytokines. Mobilization of preformed cellular stores of inflammatory cytokines 
      such as in mucosal mast cells may have an important pathophysiological role in 
      ECMO-related SIRS.
FAU - McILwain, R Britt
AU  - McILwain RB
AD  - University Hospital Services, University of Alabama at Birmingham (UAB), 
      Birmingham, AL 35294, USA.
FAU - Timpa, Joseph G
AU  - Timpa JG
FAU - Kurundkar, Ashish R
AU  - Kurundkar AR
FAU - Holt, David W
AU  - Holt DW
FAU - Kelly, David R
AU  - Kelly DR
FAU - Hartman, Yolanda E
AU  - Hartman YE
FAU - Neel, Mary Lauren
AU  - Neel ML
FAU - Karnatak, Rajendra K
AU  - Karnatak RK
FAU - Schelonka, Robert L
AU  - Schelonka RL
FAU - Anantharamaiah, G M
AU  - Anantharamaiah GM
FAU - Killingsworth, Cheryl R
AU  - Killingsworth CR
FAU - Maheshwari, Akhil
AU  - Maheshwari A
LA  - eng
GR  - C06RR15490/RR/NCRR NIH HHS/United States
GR  - K12 HD043397-06/HD/NICHD NIH HHS/United States
GR  - K12 HD043397/HD/NICHD NIH HHS/United States
GR  - R01 HD059142-01/HD/NICHD NIH HHS/United States
GR  - K12HD043397/HD/NICHD NIH HHS/United States
GR  - C06 RR015490/RR/NCRR NIH HHS/United States
GR  - RHD059142/PHS HHS/United States
GR  - R01 HD059142/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20091109
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Interleukin-8)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9007-41-4 (C-Reactive Protein)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - C-Reactive Protein/metabolism
MH  - Cell Degranulation
MH  - Cytokines/blood/genetics/*metabolism
MH  - Extracorporeal Membrane Oxygenation/*adverse effects
MH  - Female
MH  - Hemodynamics
MH  - Inflammation Mediators/blood/*metabolism
MH  - Interleukin-8/blood
MH  - Intestinal Mucosa/*metabolism
MH  - Leukocyte Count
MH  - Male
MH  - Mast Cells/metabolism
MH  - Neutrophil Activation
MH  - Osmolar Concentration
MH  - Swine
MH  - Systemic Inflammatory Response 
      Syndrome/*etiology/*metabolism/pathology/physiopathology
MH  - Time Factors
MH  - Transcriptional Activation
MH  - Tumor Necrosis Factor-alpha/biosynthesis/blood/metabolism
PMC - PMC2799549
MID - NIHMS150143
COIS- Disclosures: No conflicts of interest to disclose.
EDAT- 2009/11/11 06:00
MHDA- 2010/02/03 06:00
PMCR- 2010/07/01
CRDT- 2009/11/11 06:00
PHST- 2009/11/11 06:00 [entrez]
PHST- 2009/11/11 06:00 [pubmed]
PHST- 2010/02/03 06:00 [medline]
PHST- 2010/07/01 00:00 [pmc-release]
AID - S0023-6837(22)02558-2 [pii]
AID - 10.1038/labinvest.2009.119 [doi]
PST - ppublish
SO  - Lab Invest. 2010 Jan;90(1):128-39. doi: 10.1038/labinvest.2009.119. Epub 2009 Nov 
      9.