BACTERIAL PRIMING INCREASES LUNG INJURY IN GRAM-NEGATIVE SEPSIS

Sepsis syndrome is a leading cause of acute respiratory distress syndr ome (ARDS), but the development of acute lung injury is highly variabl e for reasons that are poorly understood. We hypothesized that nonleth al systemic exposure to gram-negative bacteria, with its consequent ac tivation of inflammatory processes, would increase functional and stru ctural lung injury on a second exposure to live organisms, as compared with exposure of naive animals. Sixteen adult baboons received 1 to 2 X 10(10) colony-forming-units (cfu)/kg Escherichia coli by intravenou s infusion. Eight animals received live bacteria as a single infusion, whereas the other eight received 10% of the total dose as heat-killed organisms (priming dose) 12 h before the live infusion. Pulmonary gas exchange and hemodynamics were monitored for 48 h or until blood pres sure could not be maintained. The animals were killed and one lung was processed for electron microscopy and morphometry. Group data were co mpared through analysis of variance (ANOVA). The systemic circulatory responses to the bacterial challenge were similar, although less sever e shock occurred in primed animals. In contrast, primed animals had in creased structural damage involving lung epithelium and endothelium, a nd showed increased cellularity of the interstitium. The morphologic e vidence of increased lung injury in septic animals with prior exposure to heat-killed bacteria suggests that prior activation of systemic in flammatory responses is a contributing factor in the pathogenesis of A RDS.