Xenon enhances hypothermic neuroprotection in asphyxiated newborn pigs.
OBJECTIVE
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 degrees C, n = 18); (2) 18 hours 50% xenon with NT (n = 12); (3) 12 hours HT (rectal temperature 33.5 degrees C, n = 18); (4) 24 hours HT (rectal temperature 33.5 degrees 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.


CONCLUSIONS
Combining xenon with HT is a promising therapy for severely encephalopathic infants, doubling the neuroprotection offered by HT alone.
Chakkarapani
Elavazhagan
E
Department of Clinical Sciences at South Bristol, University of Bristol, Bristol, United Kingdom.
Dingley
John
J
Liu
Xun
X
Hoque
Nicholas
N
Aquilina
Kristian
K
Porter
Helen
H
Thoresen
Marianne
M
D000818:Animals; D000831:Animals, Newborn; D001237:Asphyxia / Q000150:complications* / Q000473:pathology / Q000628:therapy*; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000473:pathology; D001930:Brain Injuries / Q000209:etiology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D007036:Hypothermia, Induced / Q000379:methods*; D016014:Linear Models; D009460:Neurologic Examination / Q000379:methods; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D013552:Swine; D013997:Time Factors; D014978:Xenon / Q000627:therapeutic use*
D018696:Neuroprotective Agents; D014978:Xenon