RESISTANCE OF THE ALVEOLAR EPITHELIUM TO INJURY FROM SEPTIC SHOCK IN SHEEP

Experimentally, the intravenous administration of a bolus dose of Esch erichia coil endotoxin in sheep or bolus dose of live Pseudomonas aeru ginosa in rats is insufficient to cause injury to the alveolar epithel ial barrier. Therefore, the first objective of these studies was to ma ximize the injury caused by live bacteria to the lung by administering a large dose of live P. aeruginosa into the lung perfusate of goat lu ngs in situ. P. aeruginosa (2.4 x 10(10) colony-forming units [cfu]) a nd [I-131]albumin (vascular protein tracer) were added to the lung per fusate. Even though the bacterial inoculum remained very high in this isolated perfused lung system, there was no change in the permeability to protein or clearance of fluid across the alveolar epithelium, alth ough there was an increase in lung endothelial protein permeability. T herefore, since systemic factors have been implicated in the severity and pathogenesis of septic lung injury, the second objective was to ad minister a continuous intravenous infusion of live P. aeruginosa over 8 h in intact anesthetized sheep. The eight sheep so treated exhibited an intact, functional alveolar barrier, even though there was an incr ease in lung endothelial permeability to protein and an increase in ex travascular lung water. In fact, in these eight sheep, alveolar epithe lial fluid transport was significantly greater than in control sheep. In the three other septic sheep there was injury to the alveolar epith elial barrier with an increase in permeability of the barrier to prote in, an inability to transport fluid out of the airspaces, and an even greater increase in extravascular lung water. Interestingly, the three sheep with alveolar epithelial barrier injury had more systemic injur y than did the eight sheep without alveolar epithelial barrier injury (arterial pH of 7.11 +/- 0.11 versus 7.29 +/- 0.10, p < 0.05). These r esults are: (1) comparable to our human studies in which we previously reported that the severity of systemic injury identifies which patien ts have a greater risk of developing acute lung injury; and (2) indica te that the alveolar epithelium is more resistant than the lung endoth elium to injury caused by gram-negative septic shock.