title: Prostacyclin is neither sufficient alone nor necessary to cause pulmonary dysfunction: results from infusions of prostacyclin and antiprostacyclin antibody in porcine septic shock.
abstract: 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.
  
  
  METHODS
  Experimental.
  
  
  METHODS
  Laboratory.
  
  
  METHODS
  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 1010/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.
  
  
  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 Pao2, 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 B2 concentration increased significantly in all groups during septic shock. In the antiprostacyclin antibody group, leukotriene B4 increased immediately after starting antiprostacyclin antibody infusion and reached significance at 3 hrs compared with the septic control group (p <.05). The prostacyclin infusion group had consistently lower concentrations of leukotrienes C4, D4, and E4 than all other groups.
  
  
  CONCLUSIONS
  Prostacyclin does not mediate blood gas changes, alterations of pulmonary hemodynamics, or platelet abnormalities in porcine septic shock, because antiprostacyclin antibody infusion did not change the pulmonary hypertension and hypoxemia, and infusion of prostacyclin to pathophysiologic blood concentrations did not reproduce such changes. Antiprostacyclin blockade during bacteremia significantly increased concentrations of leukotrienes C4, D4, and E4 and leukotriene B4, whereas prostacyclin infusion suppressed concentrations of leukotrienes C4, D4, and E4, suggesting that endogenous prostacyclin may blunt leukotriene release.
authors.affiliation: Department of Surgery-Division of Surgical Critical Care, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Cooper Hospital/University Medical Center, Camden, NJ, USA.
authors.forename: H S
authors.initials: HS
authors.lastname: Tran
authors.forename: J V
authors.initials: JV
authors.lastname: Quinn
authors.forename: M M
authors.initials: MM
authors.lastname: Puc
authors.forename: D S
authors.initials: DS
authors.lastname: Woolley
authors.forename: R N
authors.initials: RN
authors.lastname: Puglisi
authors.forename: G J
authors.initials: GJ
authors.lastname: Slotman
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D000959:Antihypertensive Agents / Q000276:immunology* / Q000494:pharmacology; D016470:Bacteremia / Q000503:physiopathology*; D011464:Epoprostenol / Q000276:immunology* / Q000494:pharmacology; D016905:Gram-Negative Bacterial Infections / Q000503:physiopathology; D006439:Hemodynamics; D006976:Hypertension, Pulmonary / Q000276:immunology; D007975:Leukotriene B4 / Q000097:blood; D008171:Lung Diseases / Q000276:immunology*; D016555:Matched-Pair Analysis; D011659:Pulmonary Gas Exchange / Q000276:immunology; D012128:Respiratory Distress Syndrome / Q000276:immunology; D013189:SRS-A / Q000097:blood; D012772:Shock, Septic / Q000503:physiopathology*; D013552:Swine; D013929:Thromboxane B2 / Q000097:blood
chemical_list: D000959:Antihypertensive Agents; D013189:SRS-A; D007975:Leukotriene B4; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol