Tumor necrosis factor alpha: a major contributor to the hyperdynamic circulation in prehepatic portal-hypertensive rats.
OBJECTIVE
Portal hypertension is often accompanied by a hyperdynamic circulatory syndrome. Tumor necrosis factor (TNF) alpha causes vasodilatation and a hyperdynamic state in mammals by activating nitric oxide synthesis. The aim of this study was to investigate whether TNF-alpha plays a role in developing the hyperdynamic syndrome in portal hypertension.


METHODS
Portal-hypertensive rats, induced by partial ligation of the portal vein (PVL), were used. In experiment 1, rats that underwent PVL were treated with polyclonal anti-mouse TNF-alpha or placebo intravenously the same day of the PVL operation and 24 hours before hemodynamic studies. Hemodynamic studies were performed 5 days after PVL. In experiment 2, rats that underwent PVL received anti-TNF-alpha or placebo intravenously 3 days and 24 hours before hemodynamics as in experiment 1. Hemodynamics were performed 14 days after the PVL operation. TNF-alpha blood levels were measured using a bioassay.


RESULTS
Anti-TNF-alpha treatment induced a significant increase in mean arterial pressure, heart rate, and systemic vascular resistance and a significant decrease in cardiac index, portal pressure, and TNF-alpha levels in comparison with placebo animals. No significant effects were observed in sham rats.


CONCLUSIONS
Anti-TNF-alpha treatment in rats that underwent PVL significantly blunts the development of the hyperdynamic circulation and reduces portal pressure. TNF-alpha may play a role in the hemodynamic abnormalities of portal hypertension.
Lopez-Talavera
J C
JC
Digestive and Pulmonary Diseases Section, VA Medical Center, Yale University School of Medicine, West Haven, Connecticut.
Merrill
W W
WW
Groszmann
R J
RJ
D000818:Animals; D000906:Antibodies / Q000276:immunology; D001775:Blood Circulation / Q000502:physiology*; D006439:Hemodynamics / Q000502:physiology; D006975:Hypertension, Portal / Q000503:physiopathology*; D008297:Male; D051381:Rats; D013152:Splanchnic Circulation / Q000502:physiology*; D013577:Syndrome; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*
D000906:Antibodies; D014409:Tumor Necrosis Factor-alpha