The impact of intravenous dodecafluoropentane on a murine model of acute lung injury

Acute hypoxemic respiratory failure presents therapeutic challenges due to ventilation/perfusion mismatch and shunt. The goal of management strategies is to improve arterial oxygenation, however each management strategy presents risk to patients from iatrogenic injury. Intravenous oxygen therapeutics present an appealing option to improve arterial oxygenation without these risks. We used a two-hit murine model of acute lung injury to evaluate the effect of intravenous dodecafluoropentane (NanO2) on oxygen saturation and bronchoalveolar lavage cell count and protein. Mice were given intratracheal lipopolysaccharide and 20 hours later were intubated and ventilated with high tidal volumes. NanO2 was given by bolus injection at the initiation of mechanical ventilation and again at 2 hours, while oxygen saturation was measured every 15 minutes. At the conclusion of the experiment (4 hours), a bronchoalveolar lavage was performed. There was no difference in mean O2 saturation at time zero, however the difference between the mean O2 saturation immediately prior to injection and the mean first O2 saturation after injection in the control saline group were 91% and 83%, mean difference -7.5%; whereas mean O2 saturation in the NanO2 treated group rose from 89% to 91%, mean difference +2.5%, net difference 10% [95% CI: 2.7,17.3], p=0.01). There was a statistically significant difference in cell count, but not protein, on the bronchoalveolar lavage analysis. These data show that NanO2 rapidly improves oxygen saturation in a two-hit model of acute lung injury, and shows potential as an intravenous oxygen therapeutic in the management in acute hypoxemic respiratory failure.