Rat pulmonary artery wall injury by chronic intermittent infusions of Escherichia coli endotoxin. Obliterative vasculitis and vascular occlusion.

To examine the effect of intermittent endotoxemia on rat pulmonary artery structure and hemodynamic function we infused purified Escherichia coli endotoxin on four occasions over 3 weeks (at 7-day intervals), through an indwelling catheter placed in the external jugular vein. The fourth infusion of endotoxin was associated with widespread but focal alveolar consolidation, reduced perfusion of small pulmonary arteries by lumen occlusion and obliteration, pulmonary vascular wall injury, and a peripheral leukocytosis (mean +/- SEM total leukocytes, endotoxin 133.5 +/- 23 X 10 mm3, control 12.2 +/- 1.2 X 10 mm3, p less than 0.001) in which polymorphonuclear (PMN) leukocytes predominated at the expense of lymphocytes (p2x less than 0.01). The alveolar wall was thickened and the alveolar space was consolidated by degenerating polymorphonuclear leukocytes, mononuclear cells, lipid laden alveolar macrophages, erythrocytes, fibrin, and cell debris. In regions of alveolar consolidation vessel lumens were either narrowed by subendothelial cell collections that consisted either of mononuclear cells or degenerating mural and inflammatory cells, or they were occluded by degenerating inflammatory cells and cell debris. The walls of occluded vessels were evident only by their residual elastic laminae: remnants of lysed endothelial cells lined the intima and the media consisted of degenerating mural and inflammatory cells. Capillary endothelial cells showed extensive hydropic degeneration and lysis of cell contents. Intimal precursor smooth muscle cells were hypertrophied but were not associated with the appearance of mature smooth muscle cells in the walls of small pulmonary arteries. In regions of less severe alveolar consolidation by inflammatory cells, vessel wall injury was still evident but less marked; precursor smooth muscle cells were hypertrophied; subepithelial and subendothelial collections of fluid and fibrin were present; and plasma membranes of endothelial cells were disrupted. Despite extensive pulmonary vascular injury, chronic intermittent endotoxemia did not produce the structural changes associated with pulmonary hypertension (medial thickening and appearance of medial muscle in previously nonmuscular arteries) nor a significant change in pulmonary artery pressure.