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

Basilia Zingarelli, Francesco Squadrito, Mariapatrizia Ioculano, Domenica Altavilla, Federico Bussolino, Giuseppe M. Campo, Achille P. Caputi

Research output: Contribution to journalArticle

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-a). In addition, the drug completely restored macrophage phagocytosis, improved macrophage killing and significantly inhibited leukopenia. To investigate the interaction between PAF, TNF-a 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-a 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-a and myocardial depressant factor) that are relevant to shock.

Original languageEnglish
Pages (from-to)13-19
Number of pages7
JournalEuropean Journal of Pharmacology
Volume222
Issue number1
DOIs
Publication statusPublished - Nov 3 1992

Keywords

  • L-659,989
  • Myocardial depressant factor
  • PAF (platelet-activating factor,PAF-acether)
  • Splanchnic artery occlusion shock
  • TNF-a (tumor necrosis factor)

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

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