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

Abstract

Abstract Introduction Intravenous oxygen therapeutics present an appealing option for improving arterial oxygenation in patients with acute hypoxemic respiratory failure, while limiting iatrogenic injury from conventional respiratory management. Methods We used an established two-hit murine model of acute lung injury (ARDS/VILI) to evaluate the effect of intravenous dodecafluoropentane (DDFPe) on oxygen saturation and bronchoalveolar lavage cell counts and protein levels. Twenty hours after challenge with intratracheal lipopolysaccharide, mice were intubated and ventilated with high tidal volumes (4 h) to produce acute lung injury. DDFPe (0.6 mL/kg) or saline was administered by IV bolus injection at the initiation of mechanical ventilation and again at 2 h. Oxygen saturation was measured every 15 min. Bronchoalveolar lavage was performed at the conclusion of the experiment. Results The two-hit ARDS/VILI model produced substantial inflammatory acute lung injury reflected by markedly increased bronchoalveolar lavage (BAL) cell counts compared to BAL cell counts in spontaneous breathing controls (5.29 ± 1.50 × 10–6 vs 0.74 ± 0.014 × 10–6 cells/mL) Similarly, BAL protein levels were markedly elevated in ARDS/VILI-challenged mice compared with spontaneous breathing controls (1109.27 ± 223.80 vs 129.6 ± 9.75 ng/mL). We fit a linear mixed effects model that showed a significant difference in oxygen saturation over time between DDFPe-treated mice and saline-treated mice, with separation starting after the 2-h injection. DDFPe-treated ARDS/VILI-challenged mice also exhibited significant reductions in BAL cell counts but not in BAL protein. Conclusion DDFPe improves oxygen saturation in a murine model of ARDS/VILI injury with the potential for serving as an intravenous oxygen therapeutic.