Lung Vascular Injury after Bone Marrow Embolism

We examined the role of intravascular coagulation and granulocytes in mediating the alterations in pulmonary transvascular fluid and protein exchange after an intravenous injection of bone marrow. The injection of 0.2 ml/kg of bone marrow suspension (BMS) increased pulmonary arterial pressure (Ppi) and pulmonary vascular resistance (PVR) indicating the embolization of pulmonary vessels. BMS also produced steady state increases in pulmonary lymph flow (Qlym), lymph-to-plasma concentration (L/P) ratio, and lymph protein clearance (Qlym X L/P ratio). An increase in pulmonary microvascular pressure (Pmv) produced by inflating a left atrial balloon catheter after injection of BMS produced further increases in Qlym and protein clearance without a decrease in L/P ratio, indicating that the small quantities of marrow increased lung endothelial permeability to proteins. Defibrinogenation induced by treating sheep with Ancrod prevented the increases in Qlym, L/P ratio, protein clearance, Ppi, and PVR after the injection of BMS. To test whether defibrinogenation prevented the increase in endothelial permeability, Pmv was increased after injection of BMS in Ancrod-treated sheep. In contrast to the control animals, in the defibrinogenated sheep, Qlym increased but L/P ratio decreased. In another group, the role of granulocytes in mediating the marrow-induced increase in lung vascular permeability was examined by granulocyte depletion produced with hydroxyurea. Injection of BMS resulted in an increase in Qlym and decreased in L/P ratio, changes which could be explained by increased Pmv. Therefore, granulocyte depletion, like fibrinogen depletion, also inhibited the increase in permeability. However, in contrast to defibrinogenation, granulocytopenia did not inhibit the increases in P ĵ and PVR after the marrow injection. The results indicate that fibrinogen depletion prevents pulmonary vascular obstruction after injection of BMS and the associated increase in pulmonary endothelial permeability, whereas granulocyte depletion prevents only the increase in permeability. Therefore, both intravascular coagulation and granulocytes are required for the development of lung vascular injury after bone marrow pulmonary embolism. (Circ Res 50: 830-838, 1982)