Inhibition of endogenous thromboxane synthesis by exogenous prostacyclin during endotoxemia in conscious sheep.
The relationship between prostacyclin and thromboxane activity in plasma or lymph of endotoxemia sheep was studied to better understand the physiologic significance of these two vasoactive compounds. Conscious sheep received either endotoxin alone or endotoxin plus a five-hour infusion of prostacyclin. Endotoxin alone produced a pulmonary arterial hypertension, a significant decrease in cardiac output, an increase in the lung lymph flow rate, and a leukopenia. Plasma prostacyclin and thromboxane concentrations were elevated to the same extent, while pulmonary lymph thromboxane concentrations were greater than those of prostacyclin. The administration of exogenous prostacyclin significantly attenuated the hemodynamic changes following endotoxin, but not the leukopenia. During the prostacyclin infusion, plasma and lymph prostacyclin concentration were tenfold higher than those seen with endotoxin alone, while thromboxane concentrations were six to eightfold lower. Thus, high circulating prostacyclin concentrations resulted in an inhibition of thromboxane production with an associated attenuation of the hemodynamic response to endotoxin.
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D002302:Cardiac Output; D004731:Endotoxins / Q000097:blood* / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology* / Q000502:physiology*; D004926:Escherichia coli; D007958:Leukocyte Count; D010976:Platelet Count; D011453:Prostaglandins / Q000494:pharmacology* / Q000502:physiology*; D011651:Pulmonary Artery / Q000187:drug effects; D012756:Sheep; D012772:Shock, Septic / Q000097:blood; D013929:Thromboxane B2 / Q000097:blood; D013931:Thromboxanes / Q000096:biosynthesis*; D014655:Vascular Resistance / Q000187:drug effects
D004731:Endotoxins; D011453:Prostaglandins; D013931:Thromboxanes; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol