Recent studies have demonstrated significant synergistic physiological and
biochemical effects between low-dose endotoxin (Etx) administration and ole
ic acid (OA)-induced canine lung injury. To evaluate whether this interacti
on depends on Etx priming of some key cell population, we compared the effe
cts of giving low-dose Etx both after as well as before inducing lung injur
y with OA. In addition to hemodynamic and blood-gas measurements, positron
emission tomographic imaging was used to measure edema accumulation and int
rapulmonary blood flow distribution. Biochemical measurements of the stable
metabolites of prostacyclin and thromboxane were obtained as well as measu
rements of isoprostanes and reactive sulfhydryls as evidence for possible c
oncomitant oxidant production. We found that the physiological and biochemi
cal effects of low-dose Etx developed 30-45 min after its administration, r
egardless of whether Etx was administered before or after OA. No increase i
n either isoprostane or reactive sulfhydryl production after Etx and/or OA
was detected. These data suggest that the synergistic effect of low-dose Et
x and OA-induced lung injury is not due to a priming effect of Etx.