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Anesthesiology. 2013 Aug;119(2):345-57. doi: 10.1097/ALN.0b013e318294934d.

Neither xenon nor fentanyl induces neuroapoptosis in the newborn pig brain.

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School of Clinical Sciences, University of Bristol, St. Michael's Hospital, Bristol, UK.



Some inhalation anesthetics increase apoptotic cell death in the developing brain. Xenon, an inhalation anesthetic, increases neuroprotection when combined with therapeutic hypothermia after hypoxic-ischemic brain injury in newborn animals. The authors, therefore, examined whether there was any neuroapoptotic effect of breathing 50% xenon with continuous fentanyl sedation for 24 h at normothermia or hypothermia on newborn pigs.


Twenty-six healthy pigs (<24-h old) were randomized into four groups: (1) 24  h of 50% inhaled xenon with fentanyl at hypothermia (Trec = 33.5 °C), (2) 24 h of 50% inhaled xenon with fentanyl at normothermia (Trec = 38.5 °C), (3) 24 h of fentanyl at normothermia, or (4) nonventilated juvenile controls at normothermia. Five additional nonrandomized pigs inhaled 2% isoflurane at normothermia for 24 h to verify any proapoptotic effect of inhalation anesthetics in our model. Pathological cells were morphologically assessed in cortex, putamen, hippocampus, thalamus, and white matter. To quantify the findings, immunostained cells (caspase-3 and terminal deoxynucleotidyl transferase-mediated deoxyuridine-triphosphate nick-end labeling) were counted in the same brain regions.


For groups (1) to (4), the total number of apoptotic cells was less than 5 per brain region, representing normal developmental neuroapoptosis. After immunostaining and cell counting, regression analysis showed that neither 50% xenon with fentanyl nor fentanyl alone increased neuroapoptosis. Isoflurane caused on average a 5- to 10-fold increase of immunostained cells.


At normothermia or hypothermia, neither 24 h of inhaled 50% xenon with fentanyl sedation nor fentanyl alone induces neuroapoptosis in the neonatal pig brain. Breathing 2% isoflurane increases neuroapoptosis in neonatal pigs.

[Indexed for MEDLINE]

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