Xenon attenuates cardiopulmonary bypass-induced neurologic and neurocognitive dysfunction in the rat.
BACKGROUND
With clinical data suggesting a role for excitatory amino acid neurotransmission in the pathogenesis of cardiopulmonary bypass (CPB)-associated brain injury, the current study was designed to determine whether xenon, an N-methyl-D-aspartate receptor antagonist, would attenuate CPB-induced neurologic and neurocognitive dysfunction in the rat.


METHODS
Following surgical preparation, rats were randomly divided into four groups: (1) sham rats were cannulated but did not undergo CPB; (2) CPB rats were subjected to 60 min of CPB using a membrane oxygenator receiving a gas mixture of 30% O2, 65% N2, and 5% CO2; (3) CPB + MK801 rats received MK801 (0.15 mg/kg intravenous) 15 min prior to 60 min of CPB with the same gas mixture; and (4) CPB + xenon rats underwent 60 min of CPB using an oxygenator receiving 30% O2, 60% xenon, 5% N2, and 5% CO2. Following CPB, the rats recovered for 12 days, during which they underwent standardized neurologic and neurocognitive testing (Morris water maze).


RESULTS
The sham and CPB + xenon groups had significantly better neurologic outcome compared to both the CPB and CPB + MK801 groups on postoperative days 1 and 3 (P < 0.05). Compared to the CPB group, the sham, CPB + MK801, and CPB + xenon groups had better neurocognitive outcome on postoperative days 3 and 4 (P < 0.001). By the 12th day, the neurocognitive outcome remained significantly better in the CPB + xenon group compared to the CPB group (P < 0.01).


CONCLUSIONS
These data indicate that CPB-induced neurologic and neurocognitive dysfunction can be attenuated by the administration of xenon, potentially related to its neuroprotective effect via N-methyl-D-aspartate receptor antagonism.
Ma
Daqing
D
Department of Anesthetics, Imperial College of Science, Technology and Medicine, London, United Kingdom.
Yang
Hong
H
Lynch
John
J
Franks
Nicholas P
NP
Maze
Mervyn
M
Grocott
Hilary P
HP
D000818:Animals; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D003072:Cognition Disorders / Q000517:prevention & control*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D014978:Xenon / Q000627:therapeutic use*
D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D014978:Xenon; D016291:Dizocilpine Maleate