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Bilirubin Production Is Increased in Newborn Mice Exposed to Isoflurane

Sota Iwatani, Jordan Burgess, Flora Kalish

    Neonatology
    |September 12, 2018
    PubMed

    Insights

    Isoflurane anesthesia increases liver heme oxygenase activity and bilirubin production in newborn mice. This finding may explain severe hyperbilirubinemia in infants after surgery, particularly those with hemolysis.

    Area of Science:

    • Neonatal Medicine
    • Anesthesiology
    • Biochemistry

    Background:

    • Neonatal hyperbilirubinemia, a condition of elevated bilirubin levels in newborns, can lead to neurotoxicity if untreated.
    • Newborns undergoing cardiac surgery face increased risks of hyperbilirubinemia and hemolysis.
    • Isoflurane (ISO), a common anesthetic, is known to upregulate heme oxygenase 1 (HO-1), a key enzyme in bilirubin production.

    Purpose of the Study:

    • To investigate if Isoflurane (ISO) exposure induces heme oxygenase 1 (HO-1) expression.
    • To determine if ISO exposure exacerbates bilirubin production in a hemolytic newborn mouse model.

    Main Methods:

    • Newborn mice were exposed to Isoflurane (ISO) or air.
    • Liver heme oxygenase (HO) activity and HO-1 protein levels were measured post-exposure.
    • Bilirubin production was assessed by measuring carbon monoxide excretion after heme loading.

    Main Results:

    • ISO significantly increased liver HO activity by 120% and 116% at 24 and 48 hours, respectively.
    • While HO-1 protein levels increased, the change was not statistically significant compared to controls.
    • ISO-exposed pups exhibited significantly higher bilirubin production rates (1.24-fold) and earlier peak levels after heme loading.

    Conclusions:

    • Isoflurane (ISO) exposure can induce HO-1 expression in the liver.
    • This induction may contribute to the development of severe hyperbilirubinemia in infants post-surgery, especially those experiencing hemolysis.
    Abstract

    Keywords:
    AnestheticsCardiopulmonary bypassHeme oxygenaseHemolysisHyperbilirubinemiaJaundiceNeurotoxicity

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