Association between endotoxemia and blood no in the portal circulation of cirrhotic patients: results of a pilot study.
Cirrhosis
Endotoxemia
Nitric oxide
Portal circulation
Systemic circulation
Journal
Internal and emergency medicine
ISSN: 1970-9366
Titre abrégé: Intern Emerg Med
Pays: Italy
ID NLM: 101263418
Informations de publication
Date de publication:
26 Feb 2024
26 Feb 2024
Historique:
received:
08
08
2023
accepted:
08
01
2024
medline:
27
2
2024
pubmed:
27
2
2024
entrez:
27
2
2024
Statut:
aheadofprint
Résumé
Pathophysiology of portal vein thrombosis (PVT) in cirrhosis is still not entirely understood. Elevated levels of lipopolysaccharides (LPS) in portal circulation are significantly associated with hypercoagulation, increased platelet activation and endothelial dysfunction. The aim of the study was to investigate if LPS was associated with reduced portal venous flow, the third component of Virchow's triad, and the underlying mechanism. Serum nitrite/nitrate, as a marker of nitric oxide (NO) generation, and LPS were measured in the portal and systemic circulation of 20 patients with cirrhosis undergoing transjugular intrahepatic portosystemic shunt (TIPS) procedure; portal venous flow velocity (PVV) was also measured in each patient and correlated with NO and LPS levels. Serum nitrite/nitrate and LPS were significantly higher in the portal compared to systemic circulation; a significant correlation was found between LPS and serum nitrite/nitrate (R = 0.421; p < 0.01). Median PVV before and after TIPS was 15 cm/s (6-40) and 31 cm/s (14-79), respectively. Correlation analysis of PVV with NO and LPS showed a statistically significant negative correlation of PVV with portal venous NO concentration (R = - 0.576; p = 0.020), but not with LPS. In vitro study with endothelial cells showed that LPS enhanced endothelial NO biosynthesis, which was inhibited by L-NAME, an inhibitor of NO synthase, or TAK-242, an inhibitor of TLR4, the LPS receptor; this effect was accomplished by up-regulation of eNOS and iNOS. The study shows that in cirrhosis, endotoxemia may be responsible for reduced portal venous flow via overgeneration of NO and, therefore, contribute to the development of PVT.
Identifiants
pubmed: 38409619
doi: 10.1007/s11739-024-03534-6
pii: 10.1007/s11739-024-03534-6
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : German Research Foundation (DFG)
ID : ID 403224013 - SFB 1382 (A09)
Organisme : German Federal Ministry of Education and Research (BMBF)
ID : DEEP-HCC project
Organisme : MICROB-PREDICT
ID : ID 847949
Organisme : Galaxi
ID : ID 668031
Organisme : LIVERHOPE
ID : ID 731875
Organisme : IHMCSA
ID : ID 964590
Informations de copyright
© 2024. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).
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