SYNERGISTIC HEMODYNAMIC-EFFECTS OF LOW-DOSE ENDOTOXIN AND ACUTE LUNG INJURY

We evaluated the effects of low-dose endotoxin (15 mu g/kg) on the pul monary and systemic responses to oleic acid (OA)-induced acute lung in jury in dogs. Animals given endotoxin alone (n = 5) showed a modest de crease in arterial blood pressure, but no effects on pulmonary hemodyn amics, blood gases, cardiac output, or lung water accumulation. Animal s (n = 6) given only OA (0.08 ml/kg) showed the expected development o f mild-moderate pulmonary hypertension, a comparable reduction in arte rial blood pressure, hypoxemia, increased lung water concentration, an d an altered intrapulmonary perfusion pattern, as assessed by positron emission tomography. Animals (n = 7) given the same dose of endotoxin , followed 30 min later by the same dose of OA, developed a similar in crease in lung water concentration as the group given OA alone, but fa iled to develop pulmonary hypertension or to redistribute pulmonary bl ood flow away from the edematous lung regions. In addition, arterial b lood pressure fell significantly more than in the other groups. These responses were associated with a 30-fold increase in circulating prost acyclin (assayed as 6-keto prostaglandin F(1 )alpha [PGF(1 alpha)]). T he effects on systemic blood pressure, intrapulmonary blood flow redis tribution, and eicosanoid production were eliminated by pretreating (n = 5) animals with meclofenamate (2 mg/kg). The results are consistent with a ''priming'' effect of low-dose endotoxin on the pulmonary endo thelium, with exaggerated prostacyclin production in response to a sub sequent lung injury. This interaction leads to altered intrapulmonary hemodynamics that exacerbate the development of hypoxemia, and to sign ificant decreases in systemic blood pressure. To the extent that the l ung is the most likely source of the increased prostacyclin production , the synergistic effects of low-dose endotoxin and lung injury may pr oduce a kind of ''lung shock.''.