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Role of thromboxane, prostaglandins and leukotrienes in endotoxic and septic shock

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Abstract

Intravenous bolus endotoxin elicits a marked but transient increase in plasma TxB2 and 6-keto-PGF1α in a large number of species. A smaller, delayed and more prolonged increase in TxB2 and 6-keto-PGF1α are reported in animals with septic shock, i.e., those with fecal peritonitis or cecal ligation. Thromboxane synthetase inhibitors or antagonists attenuate endotoxin-induced acute cardiopulmonary changes, the delayed increase in serum lysosomal enzymes, fibrin/fibrinogen degradation products and the thrombocytopenia in a number of species. While these drugs increase survival of rats or mice following endotoxin they do not alter survival of rats in septic shock. These results support the hypothesis that TxA2 exerts a pathophysiologic effect in shock following bolus endotoxin. In contrast, nonsteroidal antiinflammatory drugs (NSAID) and dietary essential fatty acid deficiency increase survival of rats subjected to endotoxin shock, and survival time in models of septic shock. These results also suggest that some other cyclooxygenase product(s) is involved in septic shock due to fecal peritonitis or cecal ligation. Preliminary experimental studies indicate salutary effects of leukotriene inhibitors and antagonists in endotoxin shock and in models of acute pulmonary injury. Clinical studies have demonstrated elevated plasma TxB2 and 6-keo-PGF1α concentrations in patients with septic shock, and elevated LTD4 in pulmonary edema fluid of patients with the adult respiratory distress syndrome. In view of these clinical and experimental results, clinical trials of NSAID and/or leukotriene inhibitors/antagonists should be considered.

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  1. Department of Physiology, Medical University of South Carolina, Charleston, South Carolina, USA

    H. A. Ball, J. A. Cook, W. C. Wise & P. V. Halushka

  2. Department of Pharmacology, Medical University of South Carolina, Charleston, South Carolina, USA

    H. A. Ball, J. A. Cook, W. C. Wise & P. V. Halushka

  3. Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA

    H. A. Ball, J. A. Cook, W. C. Wise & P. V. Halushka

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Ball, H.A., Cook, J.A., Wise, W.C. et al. Role of thromboxane, prostaglandins and leukotrienes in endotoxic and septic shock. Intensive Care Med 12, 116–126 (1986). https://doi.org/10.1007/BF00254925

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