Intratracheal endotoxin causes systemic inflammation in ventilated preterm lambs

Area of Science:

• Neonatal Physiology
• Pulmonary Inflammation
• Mechanical Ventilation

Background:

• Intratracheal endotoxin induces acute lung inflammation in adults.
• Mechanical ventilation can exacerbate lung inflammation, leading to systemic effects.
• The response of premature lungs to endotoxin and ventilation is not well understood.

Purpose of the Study:

• To investigate the effects of intratracheal endotoxin on preterm and near-term lamb lungs.
• To determine if systemic inflammation occurs in response to endotoxin and mechanical ventilation in immature lungs.
• To compare the inflammatory response in preterm versus near-term lambs.

Main Methods:

• Lambs at 130 days gestational age (GA) received surfactant or surfactant plus endotoxin (0.1 or 10 mg/kg) and were ventilated for 6 hours.
• Lambs at 141 days GA (near-term) were given intratracheal endotoxin (10 mg/kg), endotoxin plus high tidal volume ventilation, or intravenous endotoxin (5 microg/kg).
• Gas exchange, systemic inflammation markers, and endotoxin levels in plasma were assessed.

Main Results:

• Both endotoxin doses in preterm lambs impaired gas exchange and caused systemic inflammation.
• In near-term lambs, endotoxin alone caused lung inflammation but no systemic effects.
• Near-term lambs receiving endotoxin plus high tidal volume ventilation or intravenous endotoxin showed decreased gas exchange and systemic inflammation.
• Endotoxin was detected in plasma of preterm lambs but not near-term lambs.
• Lung inflammation was more severe in preterm animals.

Conclusions:

• Premature lungs are more susceptible to endotoxin-induced inflammation and systemic effects.
• Mechanical ventilation of endotoxin-exposed preterm lungs can lead to systemic inflammation even at low endotoxin doses.
• Immature lungs exhibit a heightened inflammatory response and systemic susceptibility compared to near-term lungs.