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The protective profile of argon, helium, and xenon in a model of neonatal asphyxia in rats*

Zhuang, Lei MD; Yang, Ting MD, PhD; Zhao, Hailin BSc; Fidalgo, António Rei PhD; Vizcaychipi, Marcela P. MD; Sanders, Robert D. MBBS, FRCA; Yu, Buwei MD; Takata, Masao MD, PhD; Johnson, Mark R. MBBS, PhD; Ma, Daqing MD, PhD

doi: 10.1097/CCM.0b013e3182452164
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Objective: Xenon provides neuroprotection in multiple animal models; however, little is known about the other noble gases. The aim of the current study was to compare xenon, argon, and helium neuroprotection in a neonatal asphyxia model in rats.

Design: Randomized controlled trial.

Setting: Laboratory.

Subjects: Seven-day-old postnatal Sprague-Dawley rats.

Interventions: Seventy percent argon, helium, xenon, or nitrogen balanced with oxygen after hypoxic–ischemic brain injury.

Measurements and Main Results: Control animals undergoing moderate hypoxic–ischemia endured reduced neuronal survival at 7 days with impaired neurologic function at the juvenile age compared with naïve animals. Severe hypoxic–ischemic damage produced a large cerebral infarction in controls. After moderate hypoxic–ischemia, all three noble gases improved cell survival, brain structural integrity, and neurologic function on postnatal day 40 compared with nitrogen. Interestingly, argon improved cell survival to naïve levels, whereas xenon and helium did not. When tested against more severe hypoxic–ischemic injury only, argon and xenon reduced infarct volume. Furthermore, postinjury body weight in moderate insult was lower in the helium-treated group compared with the naïve, control, and other noble gas treatment groups, whereas in the severe injurious setting, it is lower in both control and helium-treated groups than other groups. In the nondirectly injured hemisphere, argon, helium, and xenon increased the expression of Bcl-2, whereas helium and xenon increased Bcl-xL. In addition, Bax expression was enhanced in the control and helium groups.

Conclusions: These studies indicate that argon and xenon provide neuroprotection against both moderate and severe hypoxia–ischemic brain injury likely through prosurvival proteins synthesis.

From the Department of Anesthesiology (LZ, BY), Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; the Department of Anaesthetics, Intensive Care and Pain Medicine (LZ, TY, HZ, ARF, MPV, RDS, MT, DM), Imperial College London, Chelsea and Westminster Hospital, London, UK.; and Reproductive Biology (MRJ), Department of Surgery & Cancer, Imperial College London, Chelsea & Westminster Hospital, London, UK.

*See also p. 1965.

Drs. Zhuang, Yang, and Zhao contributed to this work equally.

This work was supported partially by a grant (10IMP01) from SPARKS, London, UK. Drs. Zhuang and Yang were supported by a scholarship from Chinese Society of Anesthesiology, Beijing, China.

The authors have not disclosed any potential conflicts of interest.

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© 2012 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins