[Evaluation of the hemodynamic effects of tumor necrosis factor alpha factor in rats with portal hypertension using the radioactive microsphere technique].
This study was aimed at investigating the effects of blocking circulating TNF on the hyperdynamic circulatory state developed in rats with portal vein stenosis (PVS), and the factors mediating the hemodynamic action of this cytokine in this setting.


METHODS
Murine antiTNF polyclonal antibodies (100 microgram) or placebo were intravenously injected into PVS rats (n = 24) before and 4 days after PVS. Hemodynamic studies were performed the day after the last antiTNF injection.


RESULTS
Short-term TNF inhibition led to reductions in cardiac index (p < 0.05) and portal venous inflow (p < 0.01), and significant increases in splanchnic and systemic vascular resistances. Portal pressure was unchanged, but portal-systemic shunting was decreased (p < 0.05).


CONCLUSIONS
TNF plays a key role in promoting the development of the hyperdynamic state of portal hypertension. The effect of TNF is mediated through an increased release of nitric oxide.
Servicio de Medicina Nuclear, Clínica Puerta de Hierro, Madrid, 28035, España.
M
M
Pérez-Páramo
J
J
Muñoz
A
A
Albillos
I
I
Rossi
M
M
Alvarez-Mon
J
J
Ortiz Berrocal
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003097:Collateral Circulation; D004353:Drug Evaluation, Preclinical; D006439:Hemodynamics / Q000187:drug effects*; D006940:Hyperemia / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D006975:Hypertension, Portal / Q000503:physiopathology / Q000628:therapy*; D007116:Immunization, Passive; D008026:Ligation; D008297:Male; D008863:Microspheres; D009569:Nitric Oxide / Q000097:blood / Q000502:physiology; D011169:Portal Vein; D051381:Rats; D017208:Rats, Wistar; D013152:Splanchnic Circulation / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects
D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide