HYPERDYNAMIC CIRCULATION OF CIRRHOTIC RATS WITH ASCITES - ROLE OF ENDOTOXIN, TUMOR-NECROSIS-FACTOR-ALPHA AND NITRIC-OXIDE

1. Hyperdynamic circulation observed in portal hypertensive states is characterized by generalized vasodilatation, increased cardiac index a nd increased systemic and regional blood flows, Endotoxin, tumour necr osis factor-alpha (TNF-alpha) and nitric oxide (NO) have been reported to be involved in the pathogenesis of hyperdynamic circulation, but t he interactions between endotoxin, TNF-alpha and NO in cirrhotic rats with ascites have never been specifically addressed. 2. This study was designed to determine systemic and portal haemodynamics and plasma le vels of endotoxin, TNF-alpha and nitrate/nitrite in cirrhotic rats wit h ascites and investigate the relationships between these substances. 3. Plasma concentrations of endotoxin, TNF-alpha and nitrate/nitrite ( an index of NO production) were determined in 25 cirrhotic rats with a scites and 17 control rats using the Limulus assay, ELISA and a colori metric assay respectively, In addition, haemodynamic studies were perf ormed in another ten cirrhotic rats with ascites and ten control rats, 4. Cirrhotic rats with ascites had hyperdynamic circulation accompani ed by increased plasma levels of endotoxin, TNF-alpha and nitrate/nitr ite, as compared with control rats. Significant correlation existed be tween plasma levels of endotoxin and nitrate/nitrite (r=0.59, P<0.0001 ) and between plasma levels of endotoxin and TNF-alpha (r=0.63, P<0.00 01), No correlation was detected between plasma levels of TNF-alpha an d nitrate/nitrite (r=0.24, P>0.05). 5. This study suggests that endoto xaemia developed in cirrhotic rats with ascites may stimulate NO forma tion directly or indirectly via cytokine cascade, and consequently par ticipate in the development and/or maintenance of hyperdynamic circula tion.