Prostacyclin is neither sufficient alone nor necessary to cause pulmonary dysfunction: Results from infusions of prostacyclin and antiprostacyclin antibody in porcine septic shock

Objective: This study evaluated whether prostacyclin is a necessary mediator of inflammation in graded bacteremia or is sufficient alone in pathophysiologic concentrations to cause the pulmonary derangement of bacteremic shock. Design: Experimental. Setting: Laboratory. Subjects: Twenty-three anesthetized adult swine. Intervensions: Swine were studied in four groups for 4 hrs: a) an anesthesia control group (n = 6); b) a septic control group (n = 6), in which 10 10 /mL Aeromonas hydrophila was infused intravenously at 0.2 mL.kg -1 .hr -1 and increased to 4.0 mL.kg -1 .hr -1 over 3 hrs; c) a prostacyclin infusion group (n = 6), which received prostacyclin infusion to match septic control plasma concentrationsclm without bacteremia; and d) an antiprostacyclin antibody group (n = 5), which received continuous Aeromonas hydrophila infusion plus antiprostacyclin antibody infusion. Measurements and Main Results: Pulmonary hemodynamics, arterial blood gases, and plasma concentrations of arachidonate metabolites were measured hourly over a 4-hr period. In the septic control group and antiprostacyclin antibody group, elevated pulmonary vascular resistance index and pulmonary artery pressure with decreased PaO 2 , as well as lower pH, were documented after 1 and 3 hrs of graded bacteremia compared with the anesthesia control group and prostacyclin infusion group (p < .05). Thromboxane B 2 concentration increased significantly in all groups during septic shock. In the antiprostacyclin antibody group, leukotriene B 4 increased immediately after starting antiprostacyclin antibody infusion and reached significance at 3 hrs compared with the septic control group (p