Inhaled nitric oxide and hypoxic brain injury in newborn piglets

Area of Science:

• Neonatal physiology
• Neuroprotection
• Cardiovascular research

Background:

• Inhaled nitric oxide (iNO) is a pulmonary vasodilator for neonatal pulmonary hypertension.
• Hypoxia and acidosis exacerbate pulmonary hypertension.
• Hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal mortality and morbidity.
• The effect of iNO on neurodevelopmental outcomes in HIE is unknown.
• Hypothermia is standard HIE neuroprotection but has limitations.

Purpose of the Study:

• To investigate if iNO improves survival and reduces brain injury in a neonatal piglet model of hypoxia.
• To assess the impact of iNO on biochemical and cellular markers of brain injury.

Main Methods:

• Neonatal piglets were exposed to hypoxia (Hx) and treated with or without iNO (20 ppm) during reoxygenation.
• Animals were maintained at normothermia or hypothermia.
• Cortical tissue was analyzed for ATP, lactate, HMGB1 (cell death marker), and water content.

Main Results:

• iNO treatment improved survival after hypoxia.
• However, surviving piglets showed increased ATP depletion, cerebral lactic acidosis, edema, and HMGB1 levels with iNO.
• Hypothermia did not mitigate these adverse effects of iNO on brain injury markers.

Conclusions:

• iNO improved survival following hypoxia in neonatal piglets.
• iNO was associated with exacerbated biochemical and cellular indicators of brain injury.
• These findings highlight potential risks of iNO in HIE, even with hypothermia.