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 < 0.001), and a rise in mean pulmonary artery pressure to 41.1 torr (P < 0.001) and in pulmonary shunting (Q̇(S)/Q̇(T)) to 29.4% (P < 0.001). Arterial oxygen tension (PaO₂) fell to 62.0 torr (P < 0.001), pulmonary lymph flow (Q̇(L)) rose to 14.0 ml/hr (P < 0.01), and lymph protein clearance (L/P·Q̇(L)) to 8.9 ml/hr (P < 0.01). Plasma thromboxane B₂ (TxB₂) increased to 2.43 ng/ml (P < 0.025) and pulmonary lymph TxB₂ to 3.02 ng/ml (P < 0.005). Hemorrhagic shock was followed by a rise in PaO₂ to 97.5 torr (P < 0.01), a fall in Q̇(S)/Q̇(T) to 7.9% (P < 0.005), Q̇(L) to 5.0 ml/hr (P < 0.05), and L/P Q̇(L) to 2.9 ml/hr (P < 0.05). During hemorrhage, plasma TxB₂ rose to 2.18 ng/ml (P < 0.005) and lymph TxB₂ to 2.32 ng/ml (P < 0.001). Infusion of ZAP during hemorrhagic shock was followed by a fall in WBC to 2,300/μl (P < 0.001); but Q̇(S)/Q̇(T), PaO₂, Q̇(L), and L/P·Q̇(L) remained unchanged. After indomethacin and ZAP, WBC fell to 3,210/μl (P < 0.001), Ppa rose to 27.0 torr (P < 0.05), Q̇(L) rose to 8.3 ml/hr (P < 0.05), and L/P·Q̇(L) rose to 5.2 ml/hr (P < 0.05), PaO₂ fell to 75.0 torr (P < 0.05) and Q̇(S)/Q̇(T) increased to 17.1% (P < 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.