The effects of prostaglandin E1 on lung injury complicating hyperdynamic sepsis in sheep.
We examined the hypothesis that PGE1 would reduce the severity of lung injury in sheep rendered septic by cecal ligation and perforation (CLP). Twenty-four to 30 h after CLP, septic lung injury was documented in 37 sheep because pulmonary lymph flow (Qlym) was increased above the baseline, nonseptic study (delta = +7.38 +/- 5.1 ml/h; p less than 0.05), whereas the lymph-to-plasma total protein ratios remained unchanged. During a subsequent 24-h "septic treatment" study period, Qlym continued to increase in an untreated study group (septic treatment minus septic delta = +10.24 +/- 4.9 ml/h; p less than 0.05), but not in sheep treated with PGE1 by continuous infusion at two doses, 1 micrograms/kg/h ("low-dose": delta Qlym = -0.04 +/- 6.1 ml/h; p = NS) and 1 microgram/kg/min ("high-dose": delta Qlym = -0.04 +/- 6.1 ml/h; p = NS. Mean pulmonary artery pressures (Ppa) increased in the untreated group during the septic treatment period (delta = +3.74 +/- 4.8 mm Hg; p less than 0.01), but not during PGE1 infusion in either of the low-dose (delta Ppa = -4.1 +/- 5.7 mm Hg; p less than 0.04) or the high-dose (delta Ppa = -0.1 +/- 6.2 mm Hg; P = NS) groups. Unlike other study groups, the PaO2 fell in the high-dose PGE1 group during the septic treatment study (delta PaO2 = -15.0 +/- 9.6 mm Hg; p less than 0.01). During a study period of drug withdrawal 24 h after the septic-treatment period, Qlym again increased in the low-dose PGE1 group such that the untreated and PGE1 groups were no longer dissimilar.(ABSTRACT TRUNCATED AT 250 WORDS)
Sibbald
W J
WJ
Richard Ivey Critical Care Trauma Centre, Victoria Hospital, London, Ontario, Canada.
Campbell
D
D
Raper
R R
RR
Rutledge
F S
FS
Cheung
H
H
D000527:Alprostadil / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001424:Bacterial Infections / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output; D006439:Hemodynamics / Q000187:drug effects; D007958:Leukocyte Count; D008171:Lung Diseases / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008196:Lymph / Q000502:physiology; D009504:Neutrophils / Q000473:pathology; D011651:Pulmonary Artery / Q000503:physiopathology; D012756:Sheep
D000527:Alprostadil