Abstract
Background:
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.
Methods:
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.
Results:
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.
Conclusion:
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.
Use of Mitochondrial Inhibitors to Demonstrate That Cytochrome Oxidase Near-Infrared Spectroscopy Can Measure Mitochondrial Dysfunction Noninvasively in the Brain