Prolonged Cardiopulmonary Bypass is Associated With Endothelial Glycocalyx Degradation.
Aged
Animals
Bone Marrow Cells
/ drug effects
Cardiopulmonary Bypass
/ adverse effects
DNA, Mitochondrial
/ blood
Endothelium
/ ultrastructure
Female
Glycocalyx
/ physiology
Humans
Interleukin-6
/ blood
Leukocyte Count
Male
Mice
Middle Aged
Neutrophils
/ pathology
Operative Time
Recombinant Proteins
/ pharmacology
Syndecan-1
/ blood
Cardiac surgery
Cardiopulmonary bypass
Damage associated molecular patterns
Endothelial glycocalyx
Neutrophils
Journal
The Journal of surgical research
ISSN: 1095-8673
Titre abrégé: J Surg Res
Pays: United States
ID NLM: 0376340
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
09
12
2019
revised:
23
01
2020
accepted:
16
02
2020
pubmed:
22
3
2020
medline:
4
9
2020
entrez:
22
3
2020
Statut:
ppublish
Résumé
The endothelial glycocalyx (EG) is involved in critical regulatory mechanisms that maintain endothelial vascular integrity. We hypothesized that prolonged cardiopulmonary bypass (CPB) may be associated with EG degradation. We performed an analysis of soluble syndecan-1 levels in relation to duration of CPB, as well as factors associated with cell stress and damage, such as mitochondrial DNA (mtDNA) and inflammation. Blood samples from subjects undergoing cardiac surgery with CPB (n = 54) were obtained before and during surgery, 4-8 h and 24 h after completion of CPB, and on postoperative day 4. Flow cytometry was used to determine subpopulations of white blood cells. Plasma levels of mtDNA were determined using quantitative polymerase chain reaction and plasma content of shed syndecan-1 was measured. To determine whether syndecan-1 was signaling white blood cells, the effect of recombinant syndecan-1 on mobilization of neutrophils from bone marrow was tested in mice. CPB is associated with increased mtDNA during surgery, increased syndecan-1 blood levels at 4-8 h, and increased white blood cell count at 4-8 h and 24 h. Correlation analysis revealed significant positive associations between time on CPB and syndecan-1 (r Longer duration of CPB is associated with increased plasma levels of soluble syndecan-1, a signal for EG degradation, which can induce neutrophil egress from the bone marrow. Development of therapy targeting EG shedding may be beneficial in patients with prolonged CPB.
Sections du résumé
BACKGROUND
The endothelial glycocalyx (EG) is involved in critical regulatory mechanisms that maintain endothelial vascular integrity. We hypothesized that prolonged cardiopulmonary bypass (CPB) may be associated with EG degradation. We performed an analysis of soluble syndecan-1 levels in relation to duration of CPB, as well as factors associated with cell stress and damage, such as mitochondrial DNA (mtDNA) and inflammation.
METHODS
Blood samples from subjects undergoing cardiac surgery with CPB (n = 54) were obtained before and during surgery, 4-8 h and 24 h after completion of CPB, and on postoperative day 4. Flow cytometry was used to determine subpopulations of white blood cells. Plasma levels of mtDNA were determined using quantitative polymerase chain reaction and plasma content of shed syndecan-1 was measured. To determine whether syndecan-1 was signaling white blood cells, the effect of recombinant syndecan-1 on mobilization of neutrophils from bone marrow was tested in mice.
RESULTS
CPB is associated with increased mtDNA during surgery, increased syndecan-1 blood levels at 4-8 h, and increased white blood cell count at 4-8 h and 24 h. Correlation analysis revealed significant positive associations between time on CPB and syndecan-1 (r
CONCLUSIONS
Longer duration of CPB is associated with increased plasma levels of soluble syndecan-1, a signal for EG degradation, which can induce neutrophil egress from the bone marrow. Development of therapy targeting EG shedding may be beneficial in patients with prolonged CPB.
Identifiants
pubmed: 32199337
pii: S0022-4804(20)30098-6
doi: 10.1016/j.jss.2020.02.011
pmc: PMC7247933
mid: NIHMS1568642
pii:
doi:
Substances chimiques
DNA, Mitochondrial
0
Interleukin-6
0
Recombinant Proteins
0
Syndecan-1
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
287-295Subventions
Organisme : NIGMS NIH HHS
ID : P30 GM106391
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL139887
Pays : United States
Organisme : NIGMS NIH HHS
ID : U54 GM115516
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL100398
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL136560
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Références
J Leukoc Biol. 2008 Jun;83(6):1404-12
pubmed: 18334539
Blood. 1999 Sep 15;94(6):2080-9
pubmed: 10477738
Ann Thorac Surg. 1993 Feb;55(2):552-9
pubmed: 8431082
Exp Mol Pathol. 2015 Dec;99(3):663-71
pubmed: 26551083
Am J Respir Cell Mol Biol. 2016 Aug;55(2):243-51
pubmed: 26934670
J Emerg Trauma Shock. 2013 Jul;6(3):171-5
pubmed: 23960372
Microvasc Res. 2019 Jul;124:37-42
pubmed: 30867134
Ann Thorac Surg. 1998 Dec;66(6):2145-52
pubmed: 9930521
J Biol Chem. 2003 Oct 17;278(42):40764-70
pubmed: 12904296
Ann Thorac Surg. 2015 Mar;99(3):926-31
pubmed: 25601655
Ann Thorac Surg. 1998 Mar;65(3):712-8
pubmed: 9527200
Ann Thorac Surg. 1998 Nov;66(5 Suppl):S17-9; discussion S25-8
pubmed: 9869436
Heart Lung Circ. 2018 Jan;27(1):122-129
pubmed: 28487062
Eur J Cardiothorac Surg. 2002 Feb;21(2):232-44
pubmed: 11825729
Biochem J. 2018 Mar 6;475(5):839-852
pubmed: 29511093
Perfusion. 2008 May;23(3):165-71
pubmed: 19029267
J Cell Mol Med. 2017 Aug;21(8):1457-1462
pubmed: 28211170
Crit Care. 2017 Jun 29;21(1):160
pubmed: 28659186
J Cell Physiol. 2019 Nov;234(11):19121-19129
pubmed: 30941770
J Clin Endocrinol Metab. 2005 May;90(5):2964-71
pubmed: 15728209
J Cardiothorac Vasc Anesth. 2008 Dec;22(6):814-22
pubmed: 18948034
Cell. 2002 Nov 27;111(5):635-46
pubmed: 12464176
Eur J Cardiothorac Surg. 2006 Apr;29(4):496-500
pubmed: 16504531
J Innate Immun. 2013;5(4):315-23
pubmed: 23486162
J Leukoc Biol. 2012 Jun;91(6):957-66
pubmed: 22427681
J Immunol. 2014 Jan 1;192(1):349-57
pubmed: 24285838
J Intern Med. 2006 Apr;259(4):393-400
pubmed: 16594907
Histol Histopathol. 2014 Feb;29(2):177-89
pubmed: 24150912
Rheumatology (Oxford). 2010 Sep;49(9):1618-31
pubmed: 20338884
Matrix Biol. 2012 Jan;31(1):3-16
pubmed: 22033227
Anesth Analg. 2002 May;94(5):1072-8
pubmed: 11973165
Front Immunol. 2019 Jun 28;10:1478
pubmed: 31316518
J Cardiothorac Vasc Anesth. 2020 Apr;34(4):912-919
pubmed: 31787433
Ann Thorac Surg. 2003 Mar;75(3):906-12
pubmed: 12645715
Pediatr Crit Care Med. 2016 Aug;17(8 Suppl 1):S272-8
pubmed: 27490610
J Mol Cell Cardiol. 2015 Nov;88:133-44
pubmed: 26449522
J Cell Mol Med. 2017 Jan;21(1):13-25
pubmed: 27558380