Gram negative pneumonia can lead to acute lung injury and perfusion abnormalities. We hypothesize that a nanocrystal suspension of G/PFC delivered IT to N and I lungs will be more homogeneously distributed at lower maximum(max) serum G levels then IV G. To test this hypothesis 22 lambs with N and acid I lungs were studied for 4 hours using 2 different drug delivery methods: N IT (n=5) and IV (n=5); I IT (n=6) and IV (n=6). Lambs were instrumented and gas ventilated. Lungs were injured with HCl acid in saline followed by liquid assisted ventilation (LAV) with perflubron (bolus FRC=20 ml/kg). G 5 mg/kg was delivered: IT (G/PFC; 20 ml/kg) and IV (aqueous injection with IT 20ml/kg PFC alone). Throughout the study serum G levels, arterial blood gases (mmHg), compliance (CDyn ml/cmH2O/kg) and mean blood pressure (MAP mmHg) were measured. Time-averaged and max serum G levels are reported. Lung G levels were measured at 4 hours and averaged across lobes. All data are expressed as means±SEM; p<0.05*. Physiologic values for the N & I lungs were: pH 7.42±0.01 & 7.39±0.01, pCO2 37±1.1 & 36±1.0, pO2 337±12 & 149±10, CDyn 0.99±0.08& 0.74±0.04, MAP 76±1.4 & 66±2.1, respectively. Distribution was more homogenous in the IT group then in the IV group.These data show that G lung levels in the N lung were higher in the IT group when compared to IV and similar in the I group.These findings were in spite of max serum levels in the IV groups 24x and 10x the level in the IT N and I groups, respectively. The results of this study demonstrate that in N and I lungs, homogeneous G lung levels can be more effectively achieved at lower serum levels when delivered IT in a G/PFC nanocrystal suspension as compared to IV administration. Table

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