Frequency-dependent ventilation heterogeneity in the acutely injured lung

Mechanical ventilation supports life-sustaining gas exchange by applying pressure fluctuations to drive gas into and out of the lungs, but may inadvertently contribute to worsening patient condition by ventilator-induced lung injury, which is associated with cyclic overdistension and collapse. Patients with preexisting lung injury are especially vulnerable due to heterogeneous alterations in mechanical properties of the injured lung, resulting in heterogeneous ventilation throughout different regions of the lung. However, the regional ventilation distribution is also frequency-dependent, such that regions overventilated at one frequency may be underventilated at another. Thus it may be possible to combine multiple frequencies of oscillatory ventilation simultaneously to improve the overall distribution throughout the injured lung. In this thesis, a computational model of the lungs was used to simulate oscillatory flow and gas transport. The model demonstrated that regional ventilation heterogeneity was sensitive to patient size, ventilation frequency, and injury severity. Furthermore it was possible to minimize risk of ventilator-induced lung injury in the model by tuning the flow amplitude at each frequency of a multi-frequency waveform. In an experimental model of acute lung injury, multi-frequency oscillatory ventilation was associated with reductions in regional lung stretch estimated from the motion in dynamic CT image sequences, as well as increased rates of regional gas exchange estimated from increased CT density during ventilation with xenon gas. In conclusion, computational models demonstrated the potential for optimization of multi-frequency waveforms to reduce lung injury, and experimental trials demonstrated evidence of improved regional ventilation with multiple simultaneous frequencies.