title: Imbalance between plasma levels of thromboxane B2 and 6-keto-prostaglandin F1 alpha during subacute endotoxin-induced hyperdynamic sepsis or multiple organ failure syndrome in sheep.
abstract: We compared the time course of plasma and pulmonary lymph levels of thromboxane B2 (TxB2) and 6-keto-prostaglandin (PG)F1 alpha during the development of either the hyperdynamic phase of sepsis or of the multiple organ failure syndrome (MOFS) associated with sepsis in 26 chronically instrumented awake sheep with intravascular catheters and a chronic pulmonary lymph fistula. Using a continuous i.v. infusion of Escherichia coli endotoxin administered at a rate of 20 ng.kg-1.min-1 (group E20, n = 9) resulted in hyperdynamic septic shock with more than 75% of animals surviving after 72 h of continuous endotoxin administration. Infusing endotoxin at a higher dosage (40 ng.kg-1.min-1; group E40, n = 9) resulted in the development of respiratory failure and MOFS with death occurring within 55 hr of endotoxemia. Eight similarly instrumented sheep served as controls. Administration of endotoxin produced within 4 hr in both endotoxin groups a significant increase in arterial plasma concentration of TxB2, which was not significantly different between both endotoxin groups. Thereafter, plasma TxB2 concentrations progressively decreased in the E20 group to reach at 36 hr values significantly lower than those measured in control sheep not given endotoxin. In the E40 group, plasma TxB2 concentrations returned to baseline values during the development of a MOFS. The time course of TxB2 concentrations in pulmonary lymph in both endotoxin groups was similar to that measured in each group in plasma. 6-Keto-PGF1 alpha concentrations in arterial plasma and pulmonary lymph were significantly higher than in controls during the first 20 hr following the start of endotoxin infusion in both endotoxin groups and were not different between these groups. Thereafter, plasma and pulmonary lymph 6-keto-PGF1 alpha concentrations progressively returned to baseline values in the E20 group and remained at these levels up to the end of the study period (72 hr). In the E40 group, plasma 6-keto-PGF1 alpha concentrations also decreased to baseline values during the second day of endotoxemia but then significantly increased in sheep that survived more than 36 hr and developed a hypodynamic septic state. During the first 24 hr of endotoxemia, the plasma TxB2/6-keto-PGF1 alpha ratio was similar in controls and in both endotoxin groups. During the second study day, TxB2/6-keto-PGF1 alpha ratio progressively decreased in both endotoxin groups to reach and maintain values significantly lower than those measured in controls at 36 hr in the E40 group and at 52 hr in E20 group.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Surgery and Anaesthesiology, University Medical Centre, Geneva, Switzerland.
authors.forename: J F
authors.initials: JF
authors.lastname: Pittet
authors.forename: D R
authors.initials: DR
authors.lastname: Morel
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood* / Q000378:metabolism; D000818:Animals; D004926:Escherichia coli; D005260:Female; D006439:Hemodynamics; D007700:Kinetics; D008168:Lung; D008196:Lymph / Q000378:metabolism; D008297:Male; D009102:Multiple Organ Failure / Q000097:blood* / Q000209:etiology; D012756:Sheep; D012772:Shock, Septic / Q000097:blood* / Q000139:chemically induced; D013929:Thromboxane B2 / Q000097:blood* / Q000378:metabolism
chemical_list: D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha