Effect of endotoxin on oleic acid lung injury does not depend on priming.

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

Effect of partial liquid ventilation on pulmonary vascular permeability and edema after experimental acute lung injury.

We evaluated the effects of partial liquid ventilation (PLV) with two different dosages of the perfluorocarbon LiquiVent (perflubron) on pulmonary vascular permeability and edema formation after oleic acid (OA)-induced acute lung injury in dogs. We used imaging with positron emission tomography to measure fractional pulmonary blood flow, lung water concentration (LWC), and the pulmonary transcapillary escape rate (PTCER) of (68)Ga-labeled transferrin at 5 and 21 h after lung injury in five dogs undergoing conventional mechanical ventilation (CMV), five dogs undergoing low-dose PLV (perflubron at 10 ml/kg), and four dogs undergoing high dose PLV (perflubron at 30 ml/kg). A positive end-expiratory pressure of 7.5 cm H(2)O was used in all dogs. After OA (0.08 ml/kg)- induced lung injury, there were no significant differences or trends for PTCER or LWC at any time when the PLV groups were compared with the CMV group. However, lung tissue myeloperoxidase activity was significantly lower in the combined PLV group than in the CMV group (p = 0.016). We conclude that after OA-induced lung injury, the addition of PLV to CMV does not directly attenuate pulmonary vascular leak or lung water accumulation. Rather, the benefits of such treatment may be due to modifications of the inflammatory response.

Role of cyclooxygenase-2 in oleic acid-induced acute lung injury.

Eicosanoid production appears to be important to both edemagenesis and the pattern of pulmonary perfusion in experimental acute lung injury (ALI). We hypothesized that these effects could be mediated by the inducible form of cyclooxygenase (COX-2). We used positron emission tomography to evaluate the pulmonary perfusion pattern in dogs given oleic acid (OA) only (n = 6), the novel COX-2 inhibitor SC-236 50 min before OA (n = 3), and SC-236 given 20 min before endotoxin (Etx), followed by OA given 30 min after Etx (n = 5). Thromboxane B(2) (TXB(2)) and prostacyclin (6-keto prostaglandin F(1alpha); 6-keto PGF(1alpha)) metabolite concentrations in plasma and lung tissue were measured in these groups and in another group given Etx + OA (n = 4). Inhibition of COX-2 before administration of OA alone or before administration of Etx and OA did not have any significant effect on plasma or lung tissue concentrations of TXB(2). However, inhibition of COX-2 prior to Etx and OA significantly reduced the plasma and lung tissue concentrations of 6-keto PGF(1alpha) as compared with those in the group given only Etx + OA. Moreover, SC-236 prevented the expected loss of perfusion redistribution associated with Etx + OA only. The effect of endotoxin on pulmonary perfusion in ALI is therefore the result of a COX-2-mediated increase in prostacyclin production in lung tissue.

Measurement of protein flux with positron emission tomography in neonates.

AIM: To determine whether abnormal transvascular protein flux can be measured with positron emission tomography (PET) in neonates with respiratory distress syndrome (RDS). METHODS: Fourteen infants with normal gas exchange (non-RDS group) underwent one PET measurement and 12 infants with RDS (the RDS group) underwent two measurements of protein flux, as determined by the pulmonary transcapillary escape rate for 68Gallium labelled transferrin (PTCER). RESULTS: The mean PTCER for the RDS infants (132 +/- 39 10(-4)/min) was significantly greater than that for infants without RDS (75 +/- 27 10(-4)/min). PTCER did not change between measurements in the infants with RDS, including five who received and responded to surfactant replacement between the two scans. CONCLUSIONS: Increased transvascular flux of large molecular weight proteins complicates RDS in preterm infants. PET provides a tool with which to evaluate the processes that contribute to pulmonary dysfunction in neonates.