The Effects of Prostaglandin E1on Lung Injury Complicating Hyperdynamic Sepsis in Sheep

Abstract

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 ( _Iym) was increased above the baseline, nonseptic study (Δ = +7.38 ± 5.1 ml/h; p < 0.05), whereas the lymph-to-plasma total protein ratios remained unchanged. During a subsequent 24-h “septic treatment” study period, _Iym continued to increase in an untreated study group (septic treatment minus septic Δ = +10.24 ± 4.9 ml/h; p < 0.05), but not in sheep treated with PGE₁ by continuous infusion at two doses, 1 µg/kg/h (“low-dose”: Δ _Iym = −0.04 ± 6.1 ml/h; p = NS) and 1 µg/kg/min (“high-dose”: Δ_Iym = −0.04 ± 6.1 ml/h; p = NS. Mean pulmonary artery pressures ( ) increased in the untreated group during the septic treatment period (Δ = +3.74 ± 4.8 mm Hg; p < 0.01), but not during PGE₁ infusion in either of the low-dose ( = −4.1 ± 5.7 mm Hg; p < 0.04) or the high-dose ( = −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 (ΔPaO₂ = −15.0 ± 9.6 mm Hg; p < 0.01). During a study period of drug withdrawal 24 h after the septic-treatment period, _Iym again increased in the low-dose PGE₁ group such that the untreated and PGE₁ groups were no longer dissimilar. We conclude that PGE₁ significantly blunted the progressive nature of sepsis-induced lung injury in sheep when administered during the evolution of this microvascular lesion.