Effects of combined selective iNOS inhibition and peroxynitrite blockade during endotoxemia in pigs

Franz Ploner, Peter Radermacher, Marc Theisen, Ilyas F. Tugtekin, Martin Matejovic, Alexander Stehr, Csaba Szabó, Garry J. Southan, Michael Georgieff, Uwe B. Brückner, Karl Träger

    Research output: Contribution to journalArticle

    15 Scopus citations

    Abstract

    We investigated the effect of mercaptoethylguanidine (MEG, 3 mg kg-1h-1), a combined selective inducible nitric oxide synthase (iNOS) inhibitor, a peroxynitrite and oxygen free radical scavenger with cyclooxygenase-inhibitor properties on intestinal and hepatic perfusion, O2 exchange, and metabolism during long-term hyperdynamic porcine endotoxemia. MEG was started 12 h after onset of endotoxemia. At baseline and after 12, 18, and 24 h of endotoxemia, hepatic arterial and portal venous blood flow, ileal mucosal-arterial PCO2 gap, portal and hepatic venous lactate/pyruvate ratio, free glutathione (GSH), and 8-isoprostanes were measured. Expired NO and plasma nitrate levels were assessed as well. MEG blunted the endotoxin-induced increase in expired NO and prevented the progressive fall in blood pressure without affecting cardiac output. It attenuated both systemic and regional venous acidosis without influencing the impairment of hepatosplanchnic metabolism nor counteracting the increase in GSH levels. In our model MEG failed to beneficially affect variables of oxidative stress.

    Original languageEnglish (US)
    Pages (from-to)130-136
    Number of pages7
    JournalShock
    Volume16
    Issue number2
    DOIs
    StatePublished - Aug 2001

    Keywords

    • Cyclooxygenase
    • Eicosanoids
    • Endotoxin
    • Glutathione
    • Lactate
    • Liver blood flow
    • Mercaptoethylguanidine
    • Nitrate
    • Nitric oxide synthase
    • Tonometry

    ASJC Scopus subject areas

    • Emergency Medicine
    • Critical Care and Intensive Care Medicine

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  • Cite this

    Ploner, F., Radermacher, P., Theisen, M., Tugtekin, I. F., Matejovic, M., Stehr, A., Szabó, C., Southan, G. J., Georgieff, M., Brückner, U. B., & Träger, K. (2001). Effects of combined selective iNOS inhibition and peroxynitrite blockade during endotoxemia in pigs. Shock, 16(2), 130-136. https://doi.org/10.1097/00024382-200116020-00008