ALTERED ALVEOLAR SURFACTANT IS AN EARLY MARKER OF ACUTE LUNG INJURY IN SEPTIC ADULT SHEEP

The purpose of this study was to characterize changes in the endogenou s surfactant system in adult sheep rendered septic via cecal ligation and perforation (CLP). Forty-eight hours after CLP, septic animals had significant increases in mean pulmonary artery pressure (PAP) (p < 0. 01), cardiac index (Cl) (p < 0.01), and arterial lactate (p < 0.05) va lues compared with their respective baseline values, while the same me asurements in a sham-operated control group did not change significant ly. The changes in the septic group were associated with significantly lower Pa-O2 (p < 0.05) and alveolar to arterial (A-a) oxygen gradient values (P < 0.01) at 48 h compared with baseline measurements. No cha nges in oxygenation occurred within the sham-operated group. Surfactan t phospholipid (PL) composition and surface activity measurements of i solated alveolar surfactant aggregate forms were similar for the two g roups at 48 h. However, the ratio of poorly functioning small aggregat e forms (SA) to superior functioning large aggregates (LA) was signifi cantly increased in the septic versus the sham-operated animals (p < 0 .01). This was associated with significantly decreased surfactant prot ein A (SP-A), B (SP-B), and C (SP-C) levels in septic versus sham-oper ated animals (p < 0.05). We conclude that sepsis-associated lung injur y resulted in altered alveolar surfactant aggregate forms. These chang es, together with altered surfactant protein levels, may represent a v ery sensitive marker of acute lung injury in high-risk patients. Furth ermore, these findings suggest that exogenous surfactant given at an e arly stage of lung injury may mitigate progressive lung dysfunction.