Platelet activating factor interaction with tumor necrosis factor and myocardial depressant factor in splanchnic artery occlusion shock.
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.
Zingarelli
B
B
Institute of Pharmacology, School of Medicine, University of Messina, Italy.
Squadrito
F
F
Ioculano
M
M
Altavilla
D
D
Bussolino
F
F
Campo
G M
GM
Caputi
A P
AP
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*
D005663:Furans; D009201:Myocardial Depressant Factor; D010972:Platelet Activating Factor; D014409:Tumor Necrosis Factor-alpha; C054893:L 659989