Inhaled nitric oxide treatment inhibits neuronal injury after meconium aspiration in piglets

• Background: Meconium aspiration-induced hypertensive lung injury is frequently associated with neuronal damage. Inhaled nitric oxide (iNO) is widely used in the treatment of pulmonary hypertension, but its effects on the brain are poorly known. Aims: The aim of this study was to determine the effects of iNO treatment on the neuronal tissue after meconium aspiration. Study design: 71 anesthetized, catheterized and ventilated newborn piglets were studied for 6 h. Thirty-five piglets were instilled with a bolus of human meconium intratracheally and 36 piglets with saline instillation served as controls. Nineteen meconium piglets and 17 control piglets were continuously treated with 20 ppm of iNO, started at 30 min after the insult. The extent of neuronal injury was analysed histologically, and the levels of brain tissue lipid peroxidation products, reduced glutathione (GSH), myeloperoxidase activity and oxidized DNA were analysed as indicators of oxidative stress. Results: iNO treatment diminished the pulmonary hypertensive response caused by meconium aspiration, but did not change systemic or carotid hemodynamics. NO administration was associated with reduced neuronal injury and diminished amount of oxidized DNA in the hippocampus of the meconium piglets. Further, iNO treatment was associated with decreased level of GSH in the cortex, but no change in lipid peroxidation production or myeloperoxidase activity was detected in any of the studied brain areas. Conclusions: Our results suggest that iNO treatment may inhibit DNA oxidation and neuronal injury in the hippocampus, associated with newborn meconium aspiration.

Nyckelord

Administration; Inhalation

Analysis of Variance

Animals

Asphyxia Neonatorum/*drug therapy/etiology

Blood Pressure

Cardiac Output

Case-Control Studies

Chromatography; High Pressure Liquid

Deoxyguanosine/analogs & derivatives/metabolism

Glutathione/metabolism

Heart Rate

Humans

Infant; Newborn

Interneurons/*pathology

Lipid Peroxidation/physiology

Meconium Aspiration Syndrome/*physiopathology

Nitric Oxide/administration & dosage/*therapeutic use

Oxidative Stress/*physiology

Peroxidase/metabolism

Spectrophotometry; Ultraviolet

Sus scrofa

Thiobarbituric Acid Reactive Substances/metabolism

MEDICINE

MEDICIN

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