Platelet activating factor interaction with tumor necrosis factor and myocardial depressant factor in splanchnic artery occlusion shock

Eur J Pharmacol. 1992 Nov 3;222(1):13-9. doi: 10.1016/0014-2999(92)90456-e.


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.

MeSH terms

  • Anesthesia
  • Animals
  • Blood Pressure / drug effects
  • Furans / pharmacology
  • Leukocyte Count / drug effects
  • Macrophages / drug effects
  • Male
  • Mice
  • Myocardial Depressant Factor / pharmacology*
  • Phagocytosis / drug effects
  • Platelet Activating Factor / antagonists & inhibitors
  • Platelet Activating Factor / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Shock / physiopathology*
  • Splanchnic Circulation / drug effects*
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / pharmacology*


  • Furans
  • Myocardial Depressant Factor
  • Platelet Activating Factor
  • Tumor Necrosis Factor-alpha
  • L 659989