title: Platelet activating factor interaction with tumor necrosis factor and myocardial depressant factor in splanchnic artery occlusion shock.
abstract: Anaesthetized rats, subjected to total occlusion of the superior mesenteric artery and the celiac trunk for 45 min, developed a severe shock state (splanchnic artery occlusion shock) resulting in a fatal outcome within 75-90 min after release of the occlusion. Shocked rats, treated with an intravenous bolus of L-659,989, a specific platelet activating factor (PAF) receptor antagonist (12.5, 25 or 50 nmol/kg, 4 min after reperfusion followed, 8 min thereafter, by a continuous infusion of 125, 250 or 500 nmol/kg for 30 min), maintained post-release mean arterial blood pressure at significantly higher values than did rats receiving the vehicle. Treatment with L-659,989 significantly increased survival rate, blunted the rise in plasma myocardial depressant factor activity and lowered serum and macrophage levels of tumor necrosis factor (TNF-alpha). In addition, the drug completely restored macrophage phagocytosis, improved macrophage killing and significantly inhibited leukopenia. To investigate the interaction between PAF, TNF-alpha and myocardial depressant factor, the blood levels of these three mediators were evaluated: shocked rats exhibited increased PAF levels with a peak at 30 min. The plasma levels of PAF peaked earlier than did either serum TNF-alpha or plasma myocardial depressant factor. Both peaks occurred 75 min after the release of occlusion. The results of this study therefore suggest that PAF is a key mediator of splanchnic artery occlusion shock and plays a permissive role in inducing the release of other factors (i.e. TNF-alpha and myocardial depressant factor) that are relevant to shock.
authors: Institute of Pharmacology, School of Medicine, University of Messina, Italy.
authors: B
authors: B
authors: Zingarelli
authors: F
authors: F
authors: Squadrito
authors: M
authors: M
authors: Ioculano
authors: D
authors: D
authors: Altavilla
authors: F
authors: F
authors: Bussolino
authors: G M
authors: GM
authors: Campo
authors: A P
authors: AP
authors: Caputi
mesh_terms: D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005663:Furans / Q000494:pharmacology; D007958:Leukocyte Count / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D009201:Myocardial Depressant Factor / Q000494:pharmacology*; D010587:Phagocytosis / Q000187:drug effects; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012769:Shock / Q000503:physiopathology*; D013152:Splanchnic Circulation / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D005663:Furans; D009201:Myocardial Depressant Factor; D010972:Platelet Activating Factor; D014409:Tumor Necrosis Factor-alpha; C054893:L 659989