Beschreibung:
<jats:title>Abstract</jats:title><jats:sec>
<jats:title>Introduction</jats:title>
<jats:p>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.</jats:p>
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<jats:title>Methods</jats:title>
<jats:p>VILI was induced in mice by high tidal-volume ventilation (HV<jats:sub>T</jats:sub> 34 ml/kg). Low tidal-volume ventilation (LV<jats:sub>T</jats:sub> 9 ml/kg) was used in control groups. PEEP was set to 2 cm H<jats:sub>2</jats:sub>O, FiO<jats:sub>2</jats:sub> was 0.5 in all groups. HV<jats:sub>T</jats:sub> and LV<jats:sub>T</jats:sub> mice were ventilated with either I:E of 1:2 (LV<jats:sub>T</jats:sub> 1:2, HV<jats:sub>T</jats:sub> 1:2) or 1:1 (LV<jats:sub>T</jats:sub> 1:1, HV<jats:sub>T</jats:sub> 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.</jats:p>
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<jats:title>Results</jats:title>
<jats:p>LV<jats:sub>T</jats:sub> 1:2 or LV<jats:sub>T</jats:sub> 1:1 did not result in VILI, and all individuals survived the ventilation period. HV<jats:sub>T</jats:sub> 1:2 decreased lung compliance, increased pulmonary neutrophils and cytokine expression, and evoked marked histologic signs of lung injury. All animals survived. HV<jats:sub>T</jats:sub> 1:1 caused further significant worsening of oxygenation, compliance and increased pulmonary proinflammatory cytokine expression, and pulmonary and blood neutrophils. In the HV<jats:sub>T</jats:sub> 1:1 group, significant mortality during mechanical ventilation was observed.</jats:p>
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<jats:title>Conclusion</jats:title>
<jats:p>According to the “baby lung” concept, mechanical ventilation-associated stress and strain in overinflated regions of ARDS lungs was simulated by using high tidal-volume ventilation. Increase of inspiratory time and I:E ratio significantly aggravated VILI in mice, suggesting an impact of a “stress/strain × time product” for the pathogenesis of VILI. Thus increasing the inspiratory time and I:E ratio should be critically considered.</jats:p>
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