Role of platelet-activating factor in the development of endothelial dysfunction in hemorrhagic hypotension and retransfusion

Csilla Csáki, Csaba Szabó, Zoltán Benyó, Arisztid G.B. Kovách

    Research output: Contribution to journalArticle

    13 Scopus citations

    Abstract

    Platelet-activating factor (PAF), an important mediator of ischemic and shock states, has been shown to prime direct and neutrophil-mediated endothelial cell injury. In the present study we investigated therefore whether PAF is involved in the development of dysfunction of the cerebrovascular endothelium in hemorrhagic hypotension and retransfusion in cats. In vitro responses of middle cerebral arteries prepared from control animals and from animals subjected to hemorrhagic hypotension with or without specific PAF antagonist WEB 2086 treatment (1 mg/kg initial bolus followed by a 0.05 mg/kg/min infusion) were studied by measuring isometric force in organ chambers containing Krebs-Henseleit solution (37°C, gassed with 95% O2- 5% CO2). Bleeding was performed in a stepwise fashion by bringing the mean arterial blood pressure to 90, 70 and 50 mmHg and maintained for 20 min at each level followed by a 20-min retransfusion. Hemorrhagic hypotension and retransfusion caused a marked attenuation of the acetylcholine- and ATP-induced endothelium-dependent relaxations of the middle cerebral artery whereas the dilations induced by the nitric oxide donor and direct vasorelaxant SIN-1, remained unaltered. In the vessels, prepared from animals which received WEB 2086 treatment during hemorrhage and retransfusion there were more pronounced cholinergic (but not purinergic) relaxations than in the untreated animals subjected to hemorrhage. SIN-1 induced relaxations remained unaltered after WEB 2086 treatment. Our results suggest that platelet-activating factor is in part involved in the pathophysiological processes leading to the development of the endothelial dysfunction in the present model of hemorrhagic hypotension and retransfusion.

    Original languageEnglish (US)
    Pages (from-to)23-31
    Number of pages9
    JournalThrombosis Research
    Volume66
    Issue number1
    DOIs
    StatePublished - Apr 1 1992

    Keywords

    • EDRF
    • PAF
    • cerebral artery
    • hemorrhagic hypotension
    • shock

    ASJC Scopus subject areas

    • Hematology

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