Acute endotoxemia following transjugular intrahepatic stent-shunt insertion is associated with systemic and cerebral vasodilatation with increased whole body nitric oxide production in critically ill cirrhotic patients.
OBJECTIVE
Transjugular intrahepatic stent-shunt (TIPSS) insertion, in patients with uncontrolled gastro-intestinal bleeding, often results in worsening of the systemic hemodynamics which can be associated with intracranial hypertension but the underlying mechanisms are unclear. This study explored the hypothesis that TIPSS insertion results in acute endotoxemia which is associated with increased nitric oxide production resulting in systemic and cerebral vasodilatation.


METHODS
Twelve patients with cirrhosis who were undergoing TIPSS for uncontrolled variceal bleeding were studied prior to and 1-h after TIPSS insertion. Changes in cardiac output (CO) and cerebral blood flow (CBF) were measured. NO production was measured using stable isotopes using l-[guanidino-(15)N(2)] arginine and l-[ureido-(13)C;5,5-(2)H(2)] citrulline infusion. The effect of pre- and post-TIPSS plasma on nitric oxide synthase (NOS) activity on human endothelial cell-line (HUVEC) was measured.


RESULTS
TIPSS insertion resulted in a significant increase in CO and CBF. Endotoxin and induced neutrophil oxidative burst increased significantly without any significant changes in cytokines. Whole body NO production increased significantly and this was associated with increased iNOS activity in the HUVEC lines. The change in NO production correlated with the changes in CO and CBF. Brain flux of ammonia increased without significant changes in arterial ammonia.


CONCLUSIONS
In conclusion, the insertion of TIPSS results in acute endotoxemia which is associated with increased nitric oxide production possibly through an iNOS dependent mechanism which may have important pathophysiological and therapeutic relevance to understanding the basis of circulatory failure in the critically ill cirrhotic patient.
Liver Failure Group, UCL Hepatology, Upper Third Medical School, UCL Medical School, Rowland Hill Street, Royal Free Hospital, London NW3 2PF, UK. r.jalan@ucl.ac.uk
R
R
Jalan
S W M
SW
Olde Damink
J C
JC
Ter Steege
D N
DN
Redhead
A
A
Lee
P C
PC
Hayes
N E P
NE
Deutz
D000208:Acute Disease; D000641:Ammonia / Q000378:metabolism; D001120:Arginine / Q000378:metabolism; D002560:Cerebrovascular Circulation; D002956:Citrulline / Q000378:metabolism; D016638:Critical Illness; D016207:Cytokines / Q000097:blood; D019446:Endotoxemia / Q000209:etiology*; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000502:physiology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019168:Portasystemic Shunt, Transjugular Intrahepatic / Q000009:adverse effects*; D014664:Vasodilation
D016207:Cytokines; D002956:Citrulline; D009569:Nitric Oxide; D000641:Ammonia; D001120:Arginine