Bjorn Gunnarsson

Comparison of lung protective ventilation strategies in a rabbit model of acute lung injury.

Objective To determine the impact of different protective and nonprotective mechanical ventilation strategies on the degree of pulmonary inflammation, oxidative damage, and hemodynamic stability in a saline lavage model of acute lung injury. Design A prospective, randomized, controlled, in vivo animal laboratory study. Setting Animal research facility of a health sciences university. Subjects Forty-six New Zealand White rabbits. Interventions Mature rabbits were instrumented with a tracheostomy and vascular catheters. Lavage-injured rabbits were randomized to receive conventional ventilation with either a) low peak end-expiratory pressure (PEEP; tidal volume of 10 mL/kg, PEEP of 2 cm H2O); b) high PEEP (tidal volume of 10 mL/kg, PEEP of 10 cm H2O); c) low tidal volume with PEEP above Pflex (open lung strategy, tidal volume of 6 mL/kg, PEEP set 2 cm H2O > Pflex); or d) high-frequency oscillatory ventilation. Animals were ventilated for 4 hrs. Lung lavage fluid and tissue samples were obtained immediately after animals were killed. Lung lavage fluid was assayed for measurements of total protein, elastase activity, tumor necrosis factor-&agr;, and malondialdehyde. Lung tissue homogenates were assayed for measurements of myeloperoxidase activity and malondialdehyde. The need for inotropic support was recorded. Measurements and Main Results Animals that received a lung protective strategy (open lung or high-frequency oscillatory ventilation) exhibited more favorable oxygenation and lung mechanics compared with the low PEEP and high PEEP groups. Animals ventilated by a lung protective strategy also showed attenuation of inflammation (reduced tracheal fluid protein, tracheal fluid elastase, tracheal fluid tumor necrosis factor-&agr;, and pulmonary leukostasis). Animals treated with high-frequency oscillatory ventilation had attenuated oxidative injury to the lung and greater hemodynamic stability compared with the other experimental groups. Conclusions Both lung protective strategies were associated with improved oxygenation, attenuated inflammation, and decreased lung damage. However, in this small-animal model of acute lung injury, an open lung strategy with deliberate hypercapnia was associated with significant hemodynamic instability.

Partial liquid ventilation with perflubron attenuates in vivo oxidative damage to proteins and lipids.

Objective: To determine the impact of partial liquid ventilation on the degree of pulmonary damage by reactive oxygen species in a model of acute lung injury caused by systemic endotoxemia. Design: A prospective, controlled, in vivo, animal laboratory study. Setting: Animal research facility of a health sciences university. Subjects: Forty New Zealand White rabbits. Interventions: Mature rabbits were anesthetized and instrumented with a tracheostomy and vascular catheters. Animals were assigned to receive either partial liquid ventilation (n = 16) with perflubron (18 mL/kg via endotracheal tube) or conventional mechanical ventilation (n = 16). Both groups were ventilated using similar strategies, with an FIO2 of 1.0 and tidal volume as required to obtain a normal PaCO2. Animals were then given 0.9 mg/kg Escherichia coli endotoxin intravenously over 30 mins. Eight uninjured instrumented and mechanically ventilated animals served as controls. Partial liquid ventilation or conventional ventilation was continued for 4 hrs before the animals were killed. Lung homogenates were analyzed for malondialdehyde (MDA) and 4‐hydroxy‐2(E)‐nonenal (4‐HNE) concentrations using a colorimetric assay. To assess protein oxidative damage, carbonyl groups in protein side chains were derivatized with 2,4‐dinitrophenylhydrazine followed by Western blotting with a dinitrophenylated‐specific primary antibody. Measurements and Main Results: MDA (713.42 ± 662 vs. 1601.4 ± 1156 nmol/g protein; p = .023) and MDA plus 4‐HNE (1480.24 ± 788 vs. 2675.2 ± 1628 nmol/g protein; p = .038) concentrations were lower in animals treated with partial liquid ventilation compared with conventionally ventilated animals, respectively. Animals treated with partial liquid ventilation exhibited attenuation of dinitrophenylated‐derivatized protein bands by Western blotting, indicating a reduction in protein oxidative damage. The presence of perfluorocarbon did not interfere with the MDA assay when assessed by independent analysis in vitro. Perflubron did not serve as a sink for peroxyl radicals produced in the aqueous phase during separate in vitro oxidation experiments. Conclusions: Partial liquid ventilation attenuates oxidative damage to lipids and proteins during experimental acute lung injury. This finding is not caused by binding of lipid peroxidation products to perflubron or by the peroxyl radical scavenging properties of perflubron.

Ventilation Strategy Affects Neutrophil Elastase Activity in Bronchoalveolar Lavage (BAL) Fluid

Ventilation Strategy Affects Neutrophil Elastase Activity in Bronchoalveolar Lavage (BAL) Fluid

Perflubron (PFOB) Protects against Fatty Acid Oxidation in a Non-Biologic, In Vitro Model

Perflubron (PFOB) Protects against Fatty Acid Oxidation in a Non-Biologic, In Vitro Model

Ventilation Strategies that Target Lung Recruitment Attenuate Pulmonary Inflammation and Tissue Injury Following Severe Endotoxemia |[bull]| 228

Introduction: Activation and sequestration of leukocytes in the lung are thought to play a significant role in the development of Acute Lung Injury and ARDS. Clinical and laboratory studies have suggested that ventilation modalities that maintain functional residual capacity, prevent alveolar collapse and minimize cyclic overdistension are associated with better outcomes. We hypothesized that ventilation strategies that optimize lung recruitment would be associated with less inflammation and lung injury. The hypothesis was tested using a rabbit model of acute alveolitis.

Partial Liquid Ventilation(PLV) Reduces Early Inflammation in Hydrocarbon Aspiration Pneumonitis 207

Introduction-PLV has been investigated in a number of laboratory and clinical settings. Those studies demonstrate a general improvement in gas exchange and lung mechanics. We have shown a reduction in early inflammatory events following treatment of experimental acute lung injury (ALI) with PLV. Experimental models frequently do not mimic human disease. Furthermore, the onset of human disease is often more temporally remote than that seen in lab studies. Hydrocarbon aspiration is a clinically important cause of ALI associated with significant morbidity and cost. The timing of onset of injury in hydrocarbon aspiration is usually reliable. We hypothesized that timely intervention with PLV in this clinically relevant model of ALI would reduce the early inflammatory events. Methods-Six NZW rabbits were sedated and the trachea exposed under local anesthesia. The trachea was punctured under direct vision and kerosene (0.15-0.2 cc/kg) was injected. The rabbits were kept in 100% O2 spontaneously breathing until the p aO2 fell below 100 torr. At that point, they were randomized to receive PLV (FC-77, 3M Corp.) or conventional ventilation (CMV). The rabbits were supported with volume expanders and pressors as needed. Following 3 hours support, the animals were sacrificed and lung tissue was frozen at-70°C for subsequent batch analysis. The tissue was homogenized in buffered saline, ultrasonified, freeze thawed and clarified. Protein content was determined by the BCA method. Myeloperoxidase activity (MPO) was determined in the supernatants in conventional fashion with o-dianisidine and H2O2 by spectrophotometry over 1 minute. Blood gases (ABG) were determined throughout the study. Average p aO2 for the last hour is presented. The data were analyzed by t-test. Results- In general, the PLV treated rabbits tended to have a higher paO2. The histologic appearance of the PLV treated lungs indicated less severe injury. Table