Background: Perinatal asphyxia is a major concern in perinatal medicine. Resuscitation and ways to prevent and minimize adverse outcomes after perinatal asphyxia are subject to extensive research. Objectives: In this study we hypothesized that, prior to hypoxia, intravenously administered nicotine might have an effect on how newborn piglets tolerate hypoxia, with regard to the time and degree of damage inflicted, due to its suggested neuroprotective abilities, and further that resuscitation with 21 compared with 100% oxygen in nicotine-pretreated animals would cause less cerebral damage. Methods: Thirty anesthetized newborn piglets were randomized to either hypoxia or control groups, and pretreatment with either saline or nicotine. In addition, the nicotine/hypoxia group was randomized to resuscitation with either 21 or 100% oxygen for 15 min following hypoxia. Results: We found significantly more necrosis in the striatum and cortex combined (p = 0.036), and in the striatum alone (p = 0.026), in the animals pretreated with nicotine and resuscitated with 100% when compared to 21% oxygen. There was no significant difference in the cerebellum. We also found significantly increased tolerance to hypoxia as measured by the time interval that the animals endured hypoxia: 103.8 ± 28.2 min in the nicotine-pretreated animals vs. 66.5 ± 19.5 minin the saline-pretreated animals (p = 0.035). Conclusion: Nicotine enhances newborn piglets’ ability to endure hypoxia, and resuscitation with 21% oxygen inflicts less necrosis than 100% oxygen. The potential neuroprotective effects of nicotine in the newborn brain should be further investigated.

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