Jacob Herrmann, Merryn H Tawhai, David W Kaczka

High frequency oscillatory ventilation (HFOV) relies on low tidal volumes cycled at supraphysiologic rates, producing fundamentally different mechanisms for gas transport and exchange compared with conventional mechanical ventilation. Despite the appeal of using low tidal volumes to mitigate the risks of ventilator-induced lung injury (VILI), HFOV has not improved mortality for most clinical indications. This may be due to non-uniform and frequency-dependent distribution of flow throughout the lung. The goal of this study was to compare parenchymal strain heterogeneity during eucapnic HFOV when using oscillatory waveforms that consisted of either a single discrete frequency or two simultaneous frequencies. We utilized on a three-dimensional, anatomically-structured canine lung model for simulating frequency-dependent ventilation distribution. Gas transport was simulated via direct alveolar ventilation, advective mixing at bifurcations, turbulent and oscillatory dispersion, and molecular diffusion. Volume amplitudes at each oscillatory frequency were iteratively optimized to attain eucapnia. Ventilation using single-frequency HFOV demonstrated increasing heterogeneity of acinar flow and CO2 elimination with frequency, for frequencies greater than the resonant frequency. For certain pairs of frequencies, a linear combination of the two corresponding ventilation distributions yielded reduced acinar strain heterogeneity compared to either frequency alone. Our model demonstrates that superposition of two simultaneous oscillatory frequencies can achieve more uniform ventilation distribution, and therefore lessen the potential for ventilator-induced lung injury, compared to traditional single-frequency HFOV.