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作者： Craig D Smallwood, Parnian Boloori-Zadeh, Maricris R Silva and Andrew Gouldstone

 

 

摘要：

BACKGROUND: Although effective in the neonatal population, exogenous pulmonary surfactant has not demonstrated a benefit in pediatric and adult subjects with hypoxic lung injury despite a sound physiologic rationale. Importantly, neonatal surfactant replacement therapy is administered in conjunction with low fractional FIO2 while pediatric/adult therapy is administered with high FIO2. We suspected a connection between FIO2 and surfactant performance. Therefore, we sought to assess a possible mechanism by which the activity of pulmonary surfactant is adversely affected by direct oxygen exposure in in vitro experiments.

 

METHODS: The mechanical performance of pulmonary surfactant was evaluated using 2 methods. First, Langmuir-Wilhelmy balance was utilized to study the reduction in surface area (δA) of surfactant to achieve a low bound value of surface tension after repeated compression and expansion cycles. Second, dynamic light scattering was utilized to measure the size of pulmonary surfactant particles in aqueous suspension. For both experiments, comparisons were made between surfactant exposed to 21% and 100% oxygen.

 

RESULTS: The δA of surfactant was 21.1 ± 2.0% and 35.8 ± 2.0% during exposure to 21% and 100% oxygen, respectively (P = .02). Furthermore, dynamic light-scattering experiments revealed a micelle diameter of 336.0 ± 12.5 μm and 280.2 ± 11.0 μm in 21% and 100% oxygen, respectively (P < .001), corresponding to a ∼16% decrease in micelle diameter following exposure to 100% oxygen.

 

CONCLUSIONS: The characteristics of pulmonary surfactant were adversely affected by short-term exposure to oxygen. Specifically, surface tension studies revealed that short-term exposure of surfactant film to high concentrations of oxygen expedited the frangibility of pulmonary surfactant, as shown with the δA. This suggests that reductions in pulmonary compliance and associated adverse effects could begin to take effect in a very short period of time. If these findings can be demonstrated in vivo, a role for reduced FIO2 during exogenous surfactant delivery may have a clinical benefit.