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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.

American Journal of Respiratory and Critical Care Medicine
|August 14, 2001
PubMed

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.

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