Combining lung-protective strategies in experimental acute lung injury: The impact of high-frequency partial liquid ventilation.

OBJECTIVE: To evaluate the independent and combined effects of high-frequency oscillatory ventilation (HFOV) and partial liquid ventilation (PLV) on gas exchange, pulmonary histopathology, inflammation, and oxidative tissue damage in an animal model of acute lung injury. DESIGN: Prospective, randomized animal study. SETTING: Research laboratory of a health sciences university. SUBJECTS: Fifty New Zealand White rabbits. INTERVENTIONS: Juvenile rabbits injured by lipopolysaccharide infusion and saline lung lavage were assigned to conventional ventilation (CMV), PLV, HFOV, or high-frequency partial liquid ventilation (HF-PLV) with a full or half dose (HF-PLV1/2) of perfluorochemical (PFC). Uninjured ventilated animals served as controls. Arterial blood gases were obtained every 30 mins during the 4-hr study. Histopathologic evaluation was performed using a lung injury scoring system. Oxidative lung injury was assessed by measuring malondialdehyde and 4-hydroxynonenal in lung homogenates. MEASUREMENTS AND MAIN RESULTS: HFOV, PLV, or a combination of both methods (HF-PLV) resulted in significantly improved oxygenation, more favorable lung histopathology, reduced neutrophil infiltration, and attenuated oxidative damage compared with CMV. HF-PLV with a full PFC dose did not provide any additional benefit compared with HFOV alone. HF-PLV1/2 was associated with decreased pulmonary leukostasis compared with HF-PLV. CONCLUSIONS: The combination of HFOV and PLV (HF-PLV) does not provide any additional benefit compared with HFOV or PLV alone in a combined model of lung injury when lung recruitment and volume optimization can be achieved. The use of a lower PFC dose (HF-PLV1/2) is associated with decreased pulmonary leukostasis compared with HF-PLV and deserves further study.

Effect of low-bias flow oscillation with partial liquid ventilation on fluoroscopic image analysis, gas exchange, and lung injury.

OBJECTIVE: To evaluate the effect of low-bias flow oscillation (LBFO) with partial liquid ventilation (PLV) on perfluorochemical evaporation, histopathology, and oxidative tissue damage in an animal model of acute lung injury. DESIGN: Prospective, randomized animal study. SETTING: Research laboratory of a health sciences university. SUBJECTS: Twelve New Zealand White rabbits. INTERVENTIONS: Juvenile rabbits were anesthetized, paralyzed, and ventilated through a tracheostomy with either high-frequency oscillatory ventilation or LBFO. Lung injury was induced by repeated saline lavage, after which perflubron was instilled through a side port of the endotracheal tube. Lateral fluoroscopic images were performed at baseline and at various postfill intervals of animals in the high-frequency oscillatory ventilation-PLV and LBFO-PLV groups. The images were digitalized for computer analysis of the Lung Lucency Index, a surrogate marker of perflubron evaporation. Histopathologic evaluation was performed using a lung-injury scoring system. Malondialdehyde was measured in lung homogenates to assess oxidative damage. MEASUREMENTS AND MAIN RESULTS: There were no significant differences in gas exchange and ventilator settings between groups throughout the experiment. At 300 mins, the high-frequency oscillatory ventilation-PLV group had a significantly higher Lung Lucency Index compared with the LBFO-PLV group in both dependent and nondependent lung regions (a high Lung Lucency Index correlates with increased perflubron loss). Malondialdehyde measurements were not different between groups. Animals treated with LBFO-PLV had a lower histopathologic lung-injury score compared with high-frequency oscillatory ventilation-PLV. CONCLUSION: LBFO-PLV is a viable mode of ventilation in a model of acute lung injury and is associated with significant preservation of perflubron in comparison with high-frequency oscillatory ventilation-PLV. The lower evaporative losses during LBFO-PLV were associated with improved histology scores.

Low bias flow oscillation with heliox in oleic acid-induced lung injury.

OBJECTIVE: To evaluate Co(2) clearance in oleic acid-induced lung injury in rabbits receiving high-frequency oscillatory ventilation with helium-oxygen mixtures through a low bias flow oscillation system designed to conserve expensive gases. DESIGN: A prospective, controlled, interventional, in vivo animal laboratory study. SETTING: Research laboratory of a health sciences university. SUBJECTS: Eight New Zealand White Rabbits. INTERVENTIONS: Lung injury (Pao(2)/Fio(2) of <250) was induced by intravenous infusion of oleic acid. Low bias flow oscillation was performed with a modified high-frequency oscillatory ventilation circuit that uses low bias flow (100 mL/kg/min) and a soda lime canister to clear CO(2). Low bias flow oscillation-heliox trials were performed with 40%, 50%, 60%, and 70% helium (balanced with oxygen) for 20 mins. Each heliox trial was preceded by a 20-min paired control trial with 40% oxygen/60% nitrogen. MEASUREMENTS AND MAIN RESULTS: Helium concentrations of 40%, 50%, 60%, and 70% decreased Paco(2) by 13% (47 +/- 7 to 41 +/- 8 torr), 17% (50 +/- 7 to 41 +/- 6 torr), 22% (49 +/- 5 to 38 +/- 7 torr), and 26% (48 +/- 7 to 35 +/- 9 torr), respectively. The gradient between partial pressure of alveolar oxygen and Pao(2) was not affected by 60% helium; however, absolute Pao(2) increased by 15%. Fluid and inotropic requirements were similar in both control and heliox low bias flow oscillation trials. CONCLUSION: Helium concentrations greater than 40% increase Co(2) clearance from oleic acid-injured lungs of rabbits during low bias flow oscillation. The low bias flow oscillation system makes this possible using 1% of the gas volume required during high-frequency oscillatory ventilation.

Perfluorooctyl bromide (perflubron) attenuates oxidative injury to biological and nonbiological systems.

OBJECTIVE: To examine whether perfluorooctyl bromide (perflubron) is capable of protecting biological and nonbiological systems against oxidative damage through a mechanism independent of its known anti-inflammatory property. DESIGN: A controlled, in vitro laboratory study. SETTING: Research laboratory of a health sciences university. SUBJECTS: Rat pulmonary artery endothelial cell cultures (biological system) and linoleic acid in sodium dodecyl sulfate micelles (nonbiological system). INTERVENTIONS: Rat pulmonary artery endothelial cells labeled with dichlorofluorescein diacetate and incubated with perflubron or culture media (control) were exposed to H2O2. H2O2-induced fluorescence of dichlorofluorescein diacetate was measured as an index of intracellular oxidative stress. In another experiment, linoleic acid in sodium dodecyl sulfate micelles was exposed to various concentrations of the azo initiator 2,2'-diazo-bis-(2-amidinopropane) dihydrochloride (2, 4, 20, and 50 mM) in the presence or absence of perflubron. Malondialdehyde measurements were obtained as a marker of oxidative damage to linoleic acid. MEASUREMENTS AND MAIN RESULTS: Cell monolayers incubated with perflubron exhibited 66.6% attenuation in intracellular fluorescence compared with controls (p < .05). Linoleic acid in sodium dodecyl sulfate micelles incubated with perflubron and exposed to 2, 4, 20, or 50 mM of 2,2'-diazo-bis-(2-amidinopropane) dihydrochloride showed less evidence of lipid peroxidation as indicated by lower malondialdehyde measurements at 240 mins (10.6%, 16%, 41%, and 14.2%, respectively) compared with controls. CONCLUSIONS: Perflubron attenuates oxidative damage to both biological and nonbiological systems. This newly recognized property of perflubron is independent of its anti-inflammatory properties.

Heliox enhances carbon dioxide clearance from lungs of normal rabbits during low bias flow oscillation.

OBJECTIVES: To evaluate carbon dioxide clearance in normal rabbits during high-frequency oscillatory ventilation with helium-oxygen mixtures by using a low bias flow oscillation (LBFO) system designed to conserve expensive gas. DESIGN: A prospective, paired-controlled, interventional, in vivo animal laboratory study. SETTING: Animal laboratory of a health science university. SUBJECTS: Twelve New Zealand White rabbits. INTERVENTIONS: Juvenile rabbits were anesthetized, paralyzed, and ventilated through a tracheostomy. LBFO was performed with a modified high-frequency oscillatory ventilation circuit that uses low bias flow (100 mL/kg) and a soda lime cartridge to clear carbon dioxide. LBFO-heliox trials were performed with 20%, 40%, 50%, 60%, and 70% helium (balanced with oxygen) for 30 mins. Each heliox trial was preceded by a paired control trial with 40% oxygen and 60% nitrogen for 30 mins. Ventilator settings in control and heliox trials were identical. During the second part of the study, four rabbits were made hypercapnic by decreasing the power (amplitude), and LBFO was performed with 70% helium against paired-control trials of 40% oxygen and 60% nitrogen. Arterial blood gases were measured at 15-min intervals and airway pressure amplitude was recorded. PaCO2 of control and heliox trials, alveolar PO2-PaO2 gradient of control, and 60% helium trials were compared by paired Student's t-test. MEASUREMENTS AND MAIN RESULTS: At constant power, amplitude was unaffected by helium. Helium concentrations of 40%, 50%, 60%, and 70% decreased PaCO2 by 12%, 33%, 36%, and 46%, respectively. Alveolar PO2-PaO2 gradient was decreased by 40% during ventilation with 60% helium. Under hypercapnic conditions, 70% helium decreased PaCO2 by 20%. CONCLUSION: Helium concentrations > or = 40% facilitate carbon dioxide clearance from lungs of normal rabbits during LBFO. This could be accomplished inexpensively with LBFO due to preservation of heliox when using this device.