Induction of severe hypoxemia and low lung recruitability for the evaluation of therapeutic ventilation strategies: a translational model of combined surfactant-depletion and ventilator-induced lung injury.

BACKGROUND: Models of hypoxemic lung injury caused by lavage-induced pulmonary surfactant depletion are prone to prompt recovery of blood oxygenation following recruitment maneuvers and have limited translational validity. We hypothesized that addition of injurious ventilation following surfactant-depletion creates a model of the acute respiratory distress syndrome (ARDS) with persistently low recruitability and higher levels of titrated "best" positive end-expiratory pressure (PEEP) during protective ventilation. METHODS: Two types of porcine lung injury were induced by lung lavage and 3 h of either protective or injurious ventilation, followed by 3 h of protective ventilation (N = 6 per group). Recruitment maneuvers (RM) and decremental PEEP trials comparing oxygenation versus dynamic compliance were performed after lavage and at 3 h intervals of ventilation. Pulmonary gas exchange function, respiratory mechanics, and ventilator-derived parameters were assessed after each RM to map the course of injury severity and recruitability. RESULTS: Lung lavage impaired respiratory system compliance (Crs) and produced arterial oxygen tensions (PaO2) of 84±13 and 80±15 (FIO2 = 1.0) with prompt increase after RM to 270-395 mmHg in both groups. After subsequent 3 h of either protective or injurious ventilation, PaO2/FIO2 was 104±26 vs. 154±123 and increased to 369±132 vs. 167±87 mmHg in response to RM, respectively. After additional 3 h of protective ventilation, PaO2/FIO2 was 120±15 vs. 128±37 and increased to 470±68 vs. 185±129 mmHg in response to RM, respectively. Subsequently, decremental PEEP titration revealed that Crs peaked at 36 ± 10 vs. 25 ± 5 ml/cm H2O with PEEP of 12 vs. 16 cmH2O, and PaO2/FIO2 peaked at 563 ± 83 vs. 334 ± 148 mm Hg with PEEP of 16 vs. 22 cmH2O in the protective vs. injurious ventilation groups, respectively. The large disparity of recruitability between groups was not reflected in the Crs nor the magnitude of mechanical power present after injurious ventilation, once protective ventilation was resumed. CONCLUSION: Addition of transitory injurious ventilation after lung lavage causes prolonged acute lung injury with diffuse alveolar damage and low recruitability yielding high titrated PEEP levels. Mimicking lung mechanical and functional characteristics of ARDS, this porcine model rectifies the constraints of single-hit lavage models and may enhance the translation of experimental research on mechanical ventilation strategies.

Measurement of gas transport kinetics in high-frequency oscillatory ventilation (HFOV) of the lung using hyperpolarized (3)He magnetic resonance imaging.

PURPOSE: To protect the patient with acute respiratory distress syndrome from ventilator associated lung injury (VALI) high-frequency oscillatory ventilation (HFOV) is used. Clinical experience has proven that HFOV is an efficient therapy when conventional artificial ventilation is insufficient. However, the optimal settings of HFOV parameters, eg, tidal volumes, pressure amplitudes and frequency for maximal lung protection, and efficient gas exchange are not established unambiguously. METHODS: In this work magnetic resonance imaging (MRI) with hyperpolarized (3)He was employed to visualize the redistribution of gas within the cadaver pig lung during HFOV. The saturated slice method was used to characterize fast gas kinetics. RESULTS: The strong differences in kinetics were observed for HFOV-driven gas exchange in comparison with diffusive gas transport (apnea). The significant regional and HFOV frequency dependence was detected for washout and gas exchange within the lungs. Gas redistribution was much faster in posterior than in anterior parts of the lungs during HFOV, in contrast to minor differences with an opposite trend observed in apnea. CONCLUSION: The method shows significant potential for visualization and quantification of gas redistribution under HFOV and may help in optimization of the parameters to improve the clinical effect of HFOV for patients.

Visualization of inert gas wash-out during high-frequency oscillatory ventilation using fluorine-19 MRI.

High-frequency oscillatory ventilation is looked upon as a lung-protective ventilation strategy. For a further clarification of the physical processes promoting gas transport, a visualization of gas flow and the distribution of ventilation are of considerable interest. Therefore, fluorine-19 magnetic resonance imaging of the imaging gas octafluorocyclobutane (C(4) F(8) ) during high-frequency oscillatory ventilation was performed in five healthy pigs. For that, a mutually compatible ventilation-imaging system was set up and transverse images were acquired every 5 sec using FLASH sequences on a 1.5 T scanner. Despite a drop in signal-to-noise ratio after the onset of high-frequency oscillatory ventilation, for each pig, the four experiments could be analyzed. A mean wash-out time (τ) at 5 Hz of 52.7 ± 18 sec and 125.9 ± 39 sec at 10 Hz, respectively, were found for regions of interest including the whole lung. This is in agreement with the clinical findings, in that wash-out of respiratory gases is significantly prolonged for increased high-frequency oscillatory ventilation frequencies. Our study could be a good starting-point for a further optimization of high-frequency oscillatory ventilation.