PURPOSE: Pulmonary surfactant serves a vital role in both biophysical and host-defense properties of the lung. Several pathways regulate surfactant homeostasis including dynamic clearance by resident alveolar macrophages. Similarly, mechanical ventilation(MV) has been shown to alter surfactant pools sizes and may result in inadvertent lung injury. It has been previously shown in a rat model that intratracheal instillation of dichloromethylene diphosphonic encapsulated liposomes(DMDP-L) results in a 70% reduction in alveolar macrophages at 72 hours, and is associated with a seven-fold increase in surfactant levels. We hypothesized that the elevated surfactant pool sizes secondary to macrophage depletion would be protective against injurious mechanical ventilation.
METHODS: Male Sprague-Dawley rats were randomized to receive either DMDP-L or control phosphate-buffered saline liposomes(PBS-L). Rats were subjected to 120 minutes of injurious MV (tidal volume = 30mL/kg, zero end-expiratory pressure, 100% FiO2) at either Day 3 or 7 after liposome administration. Blood gas measurements and peak-inspiratory pressures(PIP) were assessed throughout MV and lung compliance (Vmax) was measured at sacrifice. Bronchoalveolar lavage fluid (BALF) protein was quantified as a measure capillary leak.
RESULTS: Twenty-four rats were randomized to receive either PBS-L or DMDP-L. Overall, there were no significant differences in outcomes between day 3 and 7. All rats receiving DMDP-L tolerated MV for 120 minutes with a final mean Pa02 of 462mmHg +/− 11 and final mean PIP of 30.2 cmH20 +/− 3.9. In contrast, seven of twelve PBS-L rats were euthanized at a mean of 90 minutes with a mean PaO2 of 71mmHg +/− 16mmHg and a mean PIP of 37.4 +/− 3.5 cmH20. In the DMDP –L group, Vmax at the end of MV was significantly higher and BALF protein significantly lower.
CONCLUSION: Alveolar macrophage depletion via DMDP-L administration mitigated the physiologic dysfunction associated with MV. These results suggest a protective role of elevated endogenous surfactant pools observed in this model.
CLINICAL IMPLICATIONS: Strategies aimed at increasing surfactant pools either endogenously or through exogenous surfactant administration may prove beneficial in selected patients requiring MV.
DISCLOSURE: Cory Yamashita, None.