Introduction: Lung-protective ventilation reduced acute respiratory distress syndrome (ARDS) mortality. To minimize ventilator-induced lung injury (VILI), tidal volume is limited, high plateau pressures are avoided, and positive end-expiratory pressure (PEEP) is applied. However, the impact of specific ventilatory patterns on VILI is not well defined. Increasing inspiratory time and thereby the inspiratory/expiratory ratio (I:E ratio) may improve oxygenation, but may also be harmful as the absolute stress and strain over time increase. We thus hypothesized that increasing inspiratory time and I:E ratio aggravates VILI. Methods: VILI was induced in mice by high tidal-volume ventilation (HV T 34 ml/kg). Low tidal-volume ventilation (LV T 9 ml/kg) was used in control groups. PEEP was set to 2 cm H 2 O, FiO 2 was 0.5 in all groups. HV T and LV T mice were ventilated with either I:E of 1:2 (LV T 1:2, HV T 1:2) or 1:1 (LV T 1:1, HV T 1:1) for 4 hours or until an alternative end point, defined as mean arterial blood pressure below 40 mm Hg. Dynamic hyperinflation due to the increased I:E ratio was excluded in a separate group of animals. Survival, lung compliance, oxygenation, pulmonary permeability, markers of pulmonary and systemic inflammation (leukocyte differentiation in lung and blood, analyses of pulmonary interleukin-6, interleukin-1β, keratinocyte-derived chemokine, monocyte chemoattractant protein-1), and histopathologic pulmonary changes were analyzed. Results: LV T 1:2 or LV T 1:1 did not result in VILI, and all individuals survived the ventilation period. HV T 1:2 decreased lung compliance, increased pulmonary neutrophils and cytokine expression, and evoked marked histologic signs of lung injury. All animals survived. HV T 1:1 caused further significant worsening of oxygenation, compliance and increased pulmonary proinflammatory cytokine expression, and pulmonary and blood neutrophils. In the HV T 1:1 group, significant mortality during mechanical ventilation was observed.

Introduction: Lung-protective ventilation reduced acute respiratory distress syndrome (ARDS) mortality. To minimize ventilator-induced lung injury (VILI), tidal volume is limited, high plateau pressures are avoided, and positive end-expiratory pressure (PEEP) is applied. However, the impact of specific ventilatory patterns on VILI is not well defined. Increasing inspiratory time and thereby the inspiratory/expiratory ratio (I:E ratio) may improve oxygenation, but may also be harmful as the absolute stress and strain over time increase. We thus hypothesized that increasing inspiratory time and I:E ratio aggravates VILI. Methods: VILI was induced in mice by high tidal-volume ventilation (HV T 34 ml/kg). Low tidal-volume ventilation (LV T 9 ml/kg) was used in control groups. PEEP was set to 2 cm H 2 O, FiO 2 was 0.5 in all groups. HV T and LV T mice were ventilated with either I:E of 1:2 (LV T 1:2, HV T 1:2) or 1:1 (LV T 1:1, HV T 1:1) for 4 hours or until an alternative end point, defined as mean arterial blood pressure below 40 mm Hg. Dynamic hyperinflation due to the increased I:E ratio was excluded in a separate group of animals. Survival, lung compliance, oxygenation, pulmonary permeability, markers of pulmonary and systemic inflammation (leukocyte differentiation in lung and blood, analyses of pulmonary interleukin-6, interleukin-1β, keratinocyte-derived chemokine, monocyte chemoattractant protein-1), and histopathologic pulmonary changes were analyzed. Results: LV T 1:2 or LV T 1:1 did not result in VILI, and all individuals survived the ventilation period. HV T 1:2 decreased lung compliance, increased pulmonary neutrophils and cytokine expression, and evoked marked histologic signs of lung injury. All animals survived. HV T 1:1 caused further significant worsening of oxygenation, compliance and increased pulmonary proinflammatory cytokine expression, and pulmonary and blood neutrophils. In the HV T 1:1 group, significant mortality during mechanical ventilation was observed.

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