Budi Wiryawan

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.

The impact of mechanical ventilation strategies that minimize atelectrauma in an experimental model of acute lung injury

OBJECTIVE To evaluate whether ventilation strategies that target alveolar stabilization and prevention of atelectrauma would be associated with more favorable physiologic outcomes in a combined model of acute lung injury. METHODS Thirty-nine rabbits were instrumented and ventilated with FiO(2) of 1.0. Combined lung injury was induced by an infusion of lipopolysaccharide and tracheal saline lavage. Animals were randomized to receive conventional ventilation with tidal volume of 10 ml/kg, PEEP of 4 cm H(2)O; conventional ventilation with surfactant (Infasurf, 3 mg/kg IT); partial liquid ventilation (18 ml/kg of perflubron IT); or high-frequency oscillatory ventilation with mean airway pressure of 14 cm H(2)O and frequency of 4 Hz. Uninjured ventilated animals served as controls. Conventional ventilation with surfactant, partial liquid ventilation and control groups were ventilated with settings identical to the conventional ventilation group. Animals were studied for 4 hours, during which serial blood gas measurements were obtained. After sacrifice, lungs were harvested for injury grading by a microscopic lung injury score and measurement of 4-hydroxy-nonenal, a marker of lipid peroxidation. RESULTS Conventional ventilation resulted in hypoxia and greater evidence of lung injury. Animals treated with partial liquid ventilation, high-frequency oscillatory ventilation or conventional ventilation with surfactant had adequate oxygenation, but conventional ventilation with surfactant resulted in higher lung injury scores and increased pulmonary oxidative damage. CONCLUSION Strategies that minimize atelectrauma (partial liquid ventilation and high-frequency oscillatory ventilation) are associated with adequate oxygenation and attenuated lung injury. Surfactant improves oxygenation in comparison to conventional ventilation alone but resulted in increased injury, presumably because the inadequately low PEEP was insufficient to stabilize the alveoli during expiration.

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.