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Effects of ventilation with different positive end-expiratory pressures on cytokine expression in the preterm lamb
A S Naik1, S G Kallapur, C J Bachurski
1Children's Hospital Medical Center, Division of Pulmonary Biology, Cincinnati, Ohio 45229, USA.
Insights
Positive end-expiratory pressure (PEEP) impacts lung injury in preterm lambs. Moderate PEEP (4 cm H2O) reduced inflammation and lung injury markers during mechanical ventilation, suggesting a protective effect.
Area of Science:
- Neonatal Physiology
- Respiratory Medicine
- Biomedical Engineering
Background:
- Ventilator-induced lung injury (VILI) is a significant concern in neonatal intensive care.
- VILI is associated with increased proinflammatory cytokines in the adult lung.
- The effect of positive end-expiratory pressure (PEEP) on VILI in preterm lungs is not well understood.
Purpose of the Study:
- To investigate the impact of varying levels of PEEP on proinflammatory cytokine mRNA expression in preterm lamb lungs.
- To determine if PEEP influences markers of lung injury, such as alveolar protein and neutrophil infiltration.
- To identify an optimal PEEP level that may mitigate VILI in surfactant-treated preterm lungs.
Main Methods:
- Preterm lambs (129 ± 3 days gestation) received surfactant treatment.
- Lambs were mechanically ventilated for 2 or 7 hours with PEEP levels of 0, 4, or 7 cm H2O.
- Unventilated lambs served as controls.
- Lung tissue was analyzed for mRNA expression of interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor-alpha (TNF-α).
- Alveolar total protein and neutrophil counts were measured.
Main Results:
- Mechanical ventilation increased proinflammatory cytokine mRNA expression (IL-1β, IL-6, IL-8, TNF-α) in all ventilated preterm lambs compared to controls.
- Higher levels of alveolar protein and neutrophils were observed at 0 and 7 cm H2O PEEP compared to 4 cm H2O PEEP.
- IL-1β, IL-6, and IL-8 mRNA levels were significantly elevated in the 0 PEEP group versus the 4 PEEP group.
- A higher percentage of collapsed alveoli was found in the 0 PEEP group compared to the 4 and 7 PEEP groups.
- Ventilation with 4 cm H2O PEEP minimized the increase in proinflammatory mediators.
Conclusions:
- Mechanical ventilation exacerbates lung injury and inflammation in surfactant-treated preterm lambs.
- A PEEP level of 4 cm H2O appears to mitigate the inflammatory response and lung injury associated with mechanical ventilation in this model.
- These findings suggest that optimizing PEEP is crucial for reducing VILI in preterm infants.
Abstract:
Ventilator-induced lung injury increases proinflammatory cytokines in the adult lung. We asked if positive end-expiratory pressure (PEEP) affects proinflammatory cytokine mRNA expression in the preterm lung. Preterm lambs at 129 +/- 3 d gestation were treated with 100 mg/kg recombinant human surfactant protein-C surfactant and ventilated for 2 or 7 h with 0, 4, or 7 cm H(2)O of PEEP. Unventilated fetal lambs were used as controls. Within 2 h of ventilation, alveolar total protein and activated neutrophils were increased and expression of mRNAs for the proinflammatory cytokines interleukin (IL)-1beta, IL-6, IL-8, and tumor necrosis factor-alpha (TNF-alpha) was increased in lung tissue of all ventilated animals relative to unventilated controls. Alveolar protein and neutrophils were higher for 0 and 7 PEEP animals than 4 PEEP animals. IL-1beta, IL-6, and IL-8 mRNAs were significantly elevated in animals ventilated with 0 PEEP compared with 4 PEEP. The percentage fractional area of collapsed alveoli was significantly higher for 0 PEEP compared with 4 and 7 PEEP groups. Mechanical ventilation increased the expression of proinflammatory mediators in surfactant-treated preterm lungs and the use of 4 PEEP minimized this response.