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

• Published in: Intensive care medicine 1986-05, Vol.12 (3), p.116-126
• Main Authors: BALL, H. A, COOK, J. A, WISE, W. C, HALUSHKA, P. V
• Format: Article
• Language: English
• Subjects: 6-Ketoprostaglandin F1 alpha - metabolism; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Anti-Inflammatory Agents - pharmacology; Biological and medical sciences; Cats; Emergency and intensive care: infection, septic shock; Endotoxins - pharmacology; Fatty Acids, Essential - deficiency; Hemodynamics - drug effects; Humans; Intensive care medicine; Leukotriene B4 - metabolism; Leukotriene B4 - physiology; Medical sciences; Prostaglandins - metabolism; Prostaglandins - physiology; Rats; Shock, Septic - drug therapy; Shock, Septic - metabolism; Shock, Septic - physiopathology; SRS-A - metabolism; SRS-A - physiology; Thromboxane A2 - metabolism; Thromboxane A2 - physiology; Thromboxane B2 - physiology; Thromboxane-A Synthase - antagonists & inhibitors; Thromboxanes - metabolism; Thromboxanes - physiology
• ISSN: 0342-4642; 1432-1238
• DOI: 10.1007/bf00254925

Intravenous bolus endotoxin elicits a marked but transient increase in plasma TxB2 and 6-keto-PGF1 alpha in a large number of species. A smaller, delayed and more prolonged increase in TxB2 and 6-keto-PGF1 alpha 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-PGF1 alpha 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.