The effect of a single infusion of zymosan-activated plasma on the pulmonary microcirculation of sheep. Structure-function relationships.

Activation of the complement cascade is one of the mechanisms through which endotoxin may cause acute lung damage. The structural and functional changes following infusion of complement-activated plasma are described. In five anesthetized open-chest sheep, the authors monitored pulmonary and systemic artery pressures for 1 hour before and for 4 hours following the start of zymosan-activated plasma (ZAP) infusion (2 ml/min over a 20-minute period). Cardiac output, blood gases, and the number of circulating white cells were also measured. In addition, we took lung biopsy tissue at baseline, 7.5, 15, 30, 60, 120, 180, and 240 minutes following the start of infusion. Lung lymph flow and protein concentration were also monitored in 2 sheep. Following ZAP infusion there was an early phase of leukopenia and marked pulmonary hypertension, followed by a phase characterized by a modest increase in the flow of protein-rich lung lymph. By light microscopy pulmonary sequestration of granulocytes was evident just 7.5 minutes following the start of ZAP infusion. Peripheral lung granulocytes increased threefold above control values by 7.5 minutes, increasing to sevenfold by 30 minutes. Electron-microscopic studies showed that some of the granulocytes were disrupted, and specific and azurophilic granules were seen in the lumen. By 15 minutes endothelial damage was apparent, and intravascular monocytes were surrounded by a proteinaceous coat. Edema accumulation and an infiltration of inflammatory cells in the lungs' connective tissue regions increased to 2 hours. From 2 hours, lung injury was less marked, and the number of peripheral lung granulocytes, fewer. Sequestration of granulocytes occurred with the onset of pulmonary hypertension and leukopenia, and was most marked when lung injury was most severe. Transient endothelial damage and edema preceded the physiologic changes interpreted as an increase in pulmonary vascular permeability. Although pulmonary sequestration of granulocytes was at least as great as that with endotoxemia, unlike endotoxemia, ZAP caused only transient endothelial injury and modest changes in vascular permeability.