Hemorrhagic shock prevents lung microvascular permeability and hypoxemia associated with complement activation in the awake sheep.

The effect of hemorrhagic hypotension on pulmonary dysfunction induced by complement activation was studied in 43 awake sheep, divided into six groups: Group I (n = 6), pulmonary vascular pressure was increased by inflation of a left atrial balloon; group II (n = 9), the complement system was activated by infusion of zymosan activated plasma (ZAP); group III (n = 5), hemorrhagic shock of 50 torr was induced for 3 hr; group IV (n = 10), hemorrhagic shock was induced as in group III, and after 2 hr of shock, ZAP was infused; group V (n = 8), 5 mg/kg of indomethacin was administered before ZAP infusion; group VI (n = 5), pretreatment with indomethacin as in group V, hemorrhagic shock and ZAP as in group IV. ZAP infusion in group II led to a fall in WBC to 2,600/ml (P less than 0.001), and a rise in mean pulmonary artery pressure to 41.1 torr (P less than 0.001) and in pulmonary shunting (QS/QT) to 29.4% (P less than 0.001). Arterial oxygen tension (PaO2) fell to 62.0 torr (P less than 0.001), pulmonary lymph flow (QL) rose to 14.0 ml/hr (P less than 0.01), and lymph protein clearance (L/P.QL) to 8.9 ml/hr (P less than 0.01). Plasma thromboxane B2 (TxB2) increased to 2.43 ng/ml (P less than 0.025) and pulmonary lymph TxB2 to 3.02 ng/ml (P less than 0.005). Hemorrhagic shock was followed by a rise in PaO2 to 97.5 torr (P less than 0.01), a fall in QS/QT to 7.9% (P less than 0.005), QL to 5.0 ml/hr (P less than 0.05), and L/P QL to 2.9 ml/hr (P less than 0.05). During hemorrhage, plasma TxB2 rose to 2.18 ng/ml (P less than 0.005) and lymph TxB2 to 2.32 ng/ml (P less than 0.001). Infusion of ZAP during hemorrhagic shock was followed by a fall in WBC to 2,300/microliter (P less than 0.001); but QS/QT, PaO2, QL, and L/P.QL remained unchanged. After indomethacin and ZAP, WBC fell to 3,210/microliter (P less than 0.001), Ppa rose to 27.0 torr (P less than 0.05), QL rose to 8.3 ml/hr (P less than 0.05), and L/P.QL rose to 5.2 ml/hr (P less than 0.05). PaO2 fell to 75.0 torr (P less than 0.05) and QS/QT increased to 17.1% (P less than 0.005). The protective effect of hemorrhagic shock on ZAP-induced pulmonary dysfunction was not reversed by indomethacin. It is concluded that hemorrhagic shock prevents hypoxemia and increased pulmonary permeability induced by activation of the complement system by ZAP.