Effect of hemorrhagic hypotension on endotoxin-induced lung injury in awake sheep

Pulmonary insufficiency is a major cause for mortality and morbidity following shock and sepsis. We studied the effect of hemorrhagic shock and retransfusion on endotoxin-induced lung dysfunction. Eighteen unanesthetized sheep with chronic lung lymph fistulae were divided into 3 groups. In Group I (n = 5) hemorrhagic shock of 50 torr was induced by arterial bleeding. Shed blood was retransfused after 4 h, and the animals were observed for 5 h. In Group II (n = 7) 1 microgramg/kg E. coli endotoxin was injected intravenously, and the animals were observed for 5 h. In Group III (n = 6) hemorrhagic shock was induced similarly to Group I. After 2 h of hypotension, E. coli endotoxin was injected similarly to Group II. Blood was retransfused after 4 h. During hemorrhagic shock arterial oxygen tension (PaO2) increased from 78.0 to 94.0 torr (P less than 0.005), lymph flow (QL) decreased from 7.2 to 5.2 ml/h (P less than 0.05) and lymph protein clearance (L/P.QL) from 4.6 to 3.3 ml/h (P less than 0.05). Calculated pulmonary microvascular pressure (Pmv) decreased from 11.1 to 7.0 torr (P less than 0.05). Plasma TXB2 increased from 197 to 967 pg/ml (P less than 0.05) and lymph TXB2 from 272 to 833 pg/ml (P less than 0.05). Endotoxin infusion was followed by a fall in WBC to 2,900/microliters (P less than 0.001), rise in pulmonary artery pressure (Ppl) from 17.5 to 49.7 torr (P less than 0.005), and Pmv from 12.1 to 23.7 torr (P less than 0.01). PaO2 decreased from 78.0 to 61.0 torr (P less than 0.01), QL increased to 36.9 ml/h (P less than 0.001), and L/P.QL to 24.3 ml/h (P less than 0.001). Plasma TXB2 increased to 7,600 pg/ml (P less than 0.005) and 6-Keto PGF1 alpha to 1,519 pg/ml (P less than 0.01). Infusion of endotoxin during hemorrhagic shock was followed by a comparable fall in WBC, pulmonary hypertensive response and hypoxemia, while Pmv increased only to 19.2 torr which was significantly lower than Group II (P less than 0.05). The rise in QL to 17.4 and L/P.QL to 10.6 ml/h in response to endotoxin was also significantly lower than Group II (P less than 0.05 and P less than 0.05, respectively). Plasma and lymph TXB2 and 6-Keto PGF1 alpha were unchanged. It is concluded that hemorrhagic shock reduced endotoxin-induced pulmonary microvascular pressure, pulmonary lymph production and protein flux, while the fall in WBC, early pulmonary hypertensive phase, hypoxemia, and prostanoid production were not altered by the hypotensive insult.