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Inhaled nitric oxide and hypoxic brain injury in newborn piglets
Journal article   Open access   Peer reviewed

Inhaled nitric oxide and hypoxic brain injury in newborn piglets

Shadi N Malaeb, John R. Grothusen, Sinan Ferit Tuzer and Maria Delivoria-Papadopoulos
Nitric oxide : biology and chemistry, v 164, pp 51-59
Oct 2026
DOI: https://doi.org/10.1016/j.niox.2026.07.003
PMID: 42520886
Featured in Collection :   Drexel's Newest Publications
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https://doi.org/10.1016/j.niox.2026.07.003View
Published, Version of Record (VoR) Open Access via Drexel Libraries Read and Publish Program 2026 Open CC BY-NC V4.0

Abstract

Nitric oxide Hypoxia Brain Injury Newborn Piglet Brain Injury Hypoxia
Background Inhaled nitric oxide (iNO) is widely used as a pulmonary vasodilator to treat infants with pulmonary hypertension (PHN). Hypoxia (Hx) and acidosis increase pulmonary vascular resistance and contribute to PHN. Perinatal asphyxia and resultant hypoxic-ischemic encephalopathy (HIE) remain major causes of neonatal death and neurological impairment, and the impact of iNO on neurodevelopmental outcomes after HIE is unclear. Although hypothermia is the standard neuroprotective therapy for HIE, many infants still do not survive or continue to experience neurological impairments despite treatment. We investigated whether iNO improves survival and reduces brain injury after Hx in a neonatal piglet model. Methods Anesthetized, instrumented piglets (3-5 days old) were exposed to normoxic or hypoxic conditions for 1 h. After Hx, animals were either euthanized or reoxygenated with or without iNO (20 ppm) initiated within 10 min and continued for 4 h, while maintained at normothermia or hypothermia. Piglets were then euthanized for cortical analysis of ATP, lactate, HMGB1 (a marker of cell death), and water content using enzymatic assays, Western blotting, and drying methods, and results were compared with non-reoxygenated hypoxic animals, normoxic sham controls, and non-instrumented piglets. Results Treatment with iNO (20 ppm) starting 10 min after Hx improved survival. However, among surviving hypoxic piglets, iNO was associated with greater ATP depletion, increased cerebral lactic acidosis, more severe cerebral edema, and elevated HMGB1 expression compared with untreated hypoxic controls. Concurrent hypothermia did not mitigate these adverse effects. Conclusion iNO improved survival after Hx but was associated with worsened biochemical and cellular markers of brain injury, despite hypothermia.

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