Xenon enhances hypothermic neuroprotection in asphyxiated newborn pigs

E Chakkarapani, J Dingley, X Liu, N Hoque, K Aquilina, HJ Porter, M Thoresen

Research output: Contribution to journalArticle (Academic Journal)peer-review

131 Citations (Scopus)


To investigate whether inhaling 50% xenon during hypothermia (HT) offers better neuroprotection than xenon or HT alone.Methods: Ninety-eight newborn pigs underwent a 45-minute global hypoxic-ischemic insult severe enough to cause permanent brain injury, and 12 pigs underwent sham protocol. Pigs then received intravenous anesthesia and were randomized to 6 treatment groups: (1) normothermia (NT; rectal temperature 38.5°C, n = 18); (2) 18 hours 50% xenon with NT (n = 12); (3) 12 hours HT (rectal temperature 33.5°C, n = 18); (4) 24 hours HT (rectal temperature 33.5°C, n = 17); (5) 18 hours 50% xenon with 12 hours HT (n = 18); and (6) 18 hours 50% xenon with 24 hours HT (n = 17). Fifty percent xenon was administered via a closed circle with 30% oxygen and 20% nitrogen. After 10 hours rewarming, cooled pigs remained normothermic until terminal perfusion fixation at 72 hours. Global and regional brain neuropathology and clinical neurological scores were performed. Results: Xenon (p = 0.011) and 12 or 24 hours HT (p = 0.003) treatments offered significant histological global, and regional neuroprotection. Combining xenon with HT yielded an additive neuroprotective effect, as there was no interaction effect (p = 0.54). Combining Xenon with 24 hours HT offered 75% global histological neuroprotection with similarly improved regional neuroprotection: thalamus (100%), brainstem (100%), white matter (86%), basal ganglia (76%), cortical gray matter (74%), cerebellum (73%), and hippocampus (72%). Neurology scores improved in the 24-hour HT and combined xenon HT groups at 72 hours. Interpretation: Combining xenon with HT is a promising therapy for severely encephalopathic infants, doubling the neuroprotection offered by HT alone.
Translated title of the contributionXenon enhances hypothermic neuroprotection in asphyxiated newborn pigs
Original languageEnglish
Pages (from-to)330 - 341
Number of pages12
JournalAnnals of Neurology
Issue number3
Early online date8 Mar 2010
Publication statusPublished - Sept 2010


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