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.

Abstract. Microscopic observations show that growth delay and division delay occur on nutrient agar after Escherichia coli B has been irradiated at 3341 Å. These effects also occur in nutrient broth. A near u.v. action spectrum for growth delay in nutrient broth has been obtained. It shows a single peak at 3380 Å and is indistinguishable from the action spectrum for photo‐protection from far u.v. (2537 Å) killing in the same organism. Furthermore, photoprotected cells show a much greater growth delay than cells that have not been photoprotected. These, as well as kinetic data, suggest that the essential action of a photoprotection treatment consists in the induction of a growth‐division delay. This delay would presumably permit more time for intracellular recovery systems to operate on the far u. v. damage to nucleic acids. Liquid holding recovery (effected by holding cells in phosphate buffer after far u. v. irradiation) shows complete overlap with photoprotection. It is concluded that photoprotection and liquid holding recovery operate on the same far u. v. damage. As with photoprotection, it is probable that the essential action of a liquid holding treatment is the induction of a growth‐division delay. No photoprotection is observed of intracellular T2 bacteriophage or of E. coli Bs‐l (Hill).

A B S T R A C T The potential deleterious role of the proaggregatory vasoconstrictor, thromboxane A2, in endotoxic shock was investigated in rats. Plasma thromboxane A2 was determined by radioimmunoassay of its stable metabolite thromboxane B2. After intravenous administration of Salmonella enteritidis endotoxin (20 mg/kg), plasma thromboxane B2 levels increased from nondetectable levels (<375 pg/ml) in normal control rats to 2,054±524 pg/ml (n = 8), within 30 min to 2,071+429 at 60 min, and decreased to 1,119+319 pg/ml, at 120 min. Plasma levels of prostaglandin E also increased from 146±33 pg/ml in normal controls (n = 5) to 2,161+606 pg/ml 30 min after endotoxin (n = 5).In contrast to shocked controls, rats pretreated with imidazole, a thromboxane synthetase inhibitor, or essential fatty acid-deficient rats, which are deficient in arachidonate and its metabolites, did not exhibit significant elevations in plasma levels of thromboxane B2. Imidazole did not however inhibit endotoxininduced elevations in plasma prostaglandin E. Essential fatty acid deficiency significantly reduced mortality to lethal endotoxic shock. This refractoriness could be duplicated in normal rats pretreated with the fatty acid cyclo-oxygenase inhibitor, indomethacin (10 mg/kg), intravenously 30 min before endotoxin injection. Imidazole (30 mg/kg) administered intraperitoneally 1 h before or intravenously 30 min before endotoxin, also significantly (P < 0.01) reduced mortality from lethal endotoxin shock to 40% compared to a control mortality of 95% at 24 h. Likewise pretreatment with 13-azaprostanoic acid (30 mg/kg),

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