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Table 1.

Low and high TV +/- PEEP with RM.

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Table 2.

Low and high TV +/- PEEP with or without RM.

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Table 3.

Two hour mechanical ventilation.

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Table 4.

Two versus four hour mechanical ventilation.

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Table 5.

Lung injury scoring system[34].

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Fig 1.

Positive-pressure ventilation (2-hour).

1a No significant differences in histology lung injury scores. 1b No significant differences were noted in bronchoalveolar absolute neutrophil counts. 1c No significant differences were noted in bronchoalveolar lavage proinflammatory cytokines between all groups. 1d Bronchoalveolar lavage total protein was significantly elevated in the HTV RM group compared to the LTV RM group (p = 0.0086). 1e Bronchoalveolar lavage albumin was significantly elevated in the high tidal volume groups compared to the air control group, but not when compared to the low-tidal volume ventilation groups (p = 0.0077) 1f Pulmonary compliance was significantly higher in the low-tidal volume ventilation group (TV 8, PEEP 4, RM) compared to all other groups (p<0.0001) and in both LTV and HTV groups with RM versus no RM (p<0.0001, p = 0.0155). Data in boxplots is presented in median ± minimum and maximum values.

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Fig 2.

Positive-pressure ventilation (2-hour vs 4-hour) 2a Standardized histology scores were significantly higher in the HTV group at 4 hours compared to the air control, LTV group at 2 hours, and HTV group at 2 hours (p = 0.0002) 2b Absolute neutrophils were significantly elevated in the TV 15, PEEP 0, RM group at 4 hours, but not at 2 hours of positive-pressure ventilation (p = 0.0046) and were significantly elevated in the HTV group compared to the LTV group (p = 0.0079) 2c Bronchoalveolar lavage albumin was significantly increased in the HTV groups at 2 and 4 hours compared to the air control (p = 0.0046) 2d Proinflammatory cytokines were significantly elevated in the HTV group at 4 hours, but not at 2 hours (see text for p values) 2e Lung histology image stained with H&E. Top Left: LTV ventilation (TV 8, PEEP 4, RM (4 hour). Top Right: HTV ventilation (TV 15, PEEP 0, RM (2 hour)). Bottom: HTV ventilation (TV 15, PEEP 0, RM (4 hour)) 2f Compliance was significantly higher in the LTV group at 4 hours compared to 2 hours of ventilation (p = 0.0027) and was significantly higher in the HTV group at 2 hours compared to 4 hours of ventilation (p = 0.0007). Data in boxplots is presented in median ± minimum and maximum values. Neutrophils are denoted with an arrow, macrophages with a dotted line arrow, and proteinaceous debris with a curved line arrow.

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Fig 3.

Positive-pressure ventilation (4-hour with RM +/- PEEP).

3a Standardized histology scores were higher in all groups compared to the air control group, but not the TV 8, PEEP 4, RM group. The addition of PEEP in the LTV group resulted in a significant decrease in the histology score. 3b Absolute neutrophils were significantly elevated in the TV 15, PEEP 0, RM group compared to the air control, TV 8, PEEP 4, RM, the TV 15, PEEP 4, RM group. The addition of PEEP to the HTV group resulted in a significant decrease in absolute neutrophils. 3c BAL albumin was significantly increased in both LTV and HTV groups without PEEP compared to the air control group 3d BAL cytokines were elevated in the HTV ventilation group. 3e Pulmonary compliance in the LTV ventilation group was significantly higher compared to all other groups. 3f Left: Lung histology image stained with H&E of low tidal volume (TV 8, PEEP 4, RM) showing influx of macrophages within the airway. Right: Lung histology image stained with H&E of high tidal (TV 15, PEEP 0, RM) showing neutrophils, proteinaceous debris, and hemorrhage within the airway. Neutrophils are denoted with an arrow, macrophages with a dotted line arrow, and proteinaceous debris with a curved line arrow.

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Fig 4.

Positive-pressure ventilation (4-hour +/- PEEP and +/- RM).

4a Standardized histology scores were increased in all groups except the low-tidal volume ventilation group (TV 8, PEEP 4, RM) compared to the air control group (not shown) and the LTV RM group. 4b Bronchoalveolar lavage absolute neutrophil counts were significantly increased in the LTV group with no RM and both HTV groups compared to the air control group. 4c Bronchoalveolar lavage albumin was significantly increased in both HTV groups compared to the air control group. 4d Proinflammatory cytokines were significantly increased in the HTV group with no RM. 4e Pulmonary compliance was significantly elevated in the LTV ventilation group compared to all other groups. Lung histology sections are shown from all groups. 4f Left: Lung histology section stained with H&E of LTV with no RM showing macrophages within the airway. Right: Lung histology section stained with H&E of HTV with no RM showing proteinaceous debris within the airway. Neutrophils are denoted with an arrow, macrophages with a dotted line arrow, and proteinaceous debris with a curved line arrow.

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