Hyperdynamic circulation in prehepatic portal hypertension: role of tumor necrosis factor-alpha.
BACKGROUND
Portal hypertension is associated with a hyperdynamic circulation characterized by increased cardiac output and reduced systemic vascular resistance. Tumor necrosis factor-alpha (TNF-alpha) is a peptide mediator released by mononuclear cells on activation by endotoxin, tissue injury and malignancy. This cytokine induces vasodilatation by activating nitric oxide synthesis. The aim of this study is to investigate if TNF-alpha is involved in the pathogenesis of hyperdynamic circulation observed in portal vein-ligated (PVL) rats.


METHODS
Systemic and portal hemodynamics were determined in seven PVL and five sham-operated (SHAM) rats using a thermodilution technique. In addition, plasma TNF-alpha concentrations were determined in another 34 PVL and 16 SHAM rats using commercially available enzyme-linked immunosorbent assay.


RESULTS
PVL rats had a significantly lower mean arterial pressure (109 +/- 17 mmHg vs. 133 +/- 12 mmHg, p < 0.001) and systemic vascular resistance (2.5 +/- 0.6 mmHg.ml-1.min.100 g BW vs. 4.6 +/- 0.8 mmHg.ml-1.min.100 g BW, p < 0.001) accompanied by a significantly higher portal pressure (14 +/- 1.9 mmHg vs. 9 +/- 2.1 mmHg, p < 0.001) and cardiac index (47.0 +/- 12.1 ml.min-1.100 g BW-1 vs. 29.3 +/- 3.5 ml.min-1.100 g BW-1, p < 0.001) when compared with SHAM rats. Also, PVL rats had significantly higher plasma levels of TNF-alpha as compared with SHAM rats (13.8 +/- 0.9 pg/ ml vs. 11.1 +/- 0.5 pg/ml, p < 0.05).


CONCLUSIONS
This study suggests that elevated plasma levels of TNF-alpha observed in PVL rats may participate in the development and/or maintenance of the hyperdynamic circulation occurring in prehepatic portal hypertension.
Chu
C J
CJ
Department of Medicine, Veterans General Hospital-Taipei, Taiwan, R.O.C.
Lee
F Y
FY
Chang
F Y
FY
Wang
S S
SS
Lin
H C
HC
Wu
S L
SL
Tai
C C
CC
Lee
S D
SD
D000818:Animals; D001794:Blood Pressure; D002302:Cardiac Output; D006439:Hemodynamics; D006975:Hypertension, Portal / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D014655:Vascular Resistance
D014409:Tumor Necrosis Factor-alpha