659 - Long-term alterations in respiration in a Gunn rat model of neonatal jaundice
Monday, April 28, 2025
7:00am – 9:15am HST
Publication Number: 659.6012
Anushka Shah, Case Western Reserve University School of Medicine, Cleveland, OH, United States; Mrinaj Janampalli, Case Western Reserve University School of Medicine, Cleveland, OH, United States; Nicholas Rickman, Case Western Reserve University School of Medicine, Oakbrook Terrace, IL, United States; Catherine Mayer, UH Rainbow Babies & Children's Hospital, Cleveland, OH, United States; Peter M. MacFarlane, Case Western Reserve University School of Medicine, Cleveland, OH, United States; Cynthia Bearer, UH Rainbow Babies & Children's Hospital/Case Western Reserve University, Cleveland, OH, United States
Research Assistant Case Western Reserve University School of Medicine Cleveland, Ohio, United States
Background: Apnea of prematurity (AOP) is a common respiratory morbidity in preterm infants, which can be exacerbated in neonates with hyperbilirubinemia. The homozygous Gunn rat (jj) lacks the ability to conjugate bilirubin which results in the accumulation of unconjugated bilirubin bound to albumin. Administration of sulfadimethoxine (SDMX) displaces bilirubin from albumin and results in acute elevation of free bilirubin (Bf), which can cross the blood brain barrier and affect the brain. Using our Gunn rat model, we have previously shown that total serum bilirubin (TsB) concentration is significantly decreased 24 hours after treatment with SDMX and recovers back to near baseline levels within 48 hours after treatment indicating the entry of Bf to the brain. Since bilirubin accumulates in the brain, we investigated whether short term hyper-bilirubinemia has a long-term impairment of respiratory neural control mechanisms. Objective: To investigate the long-term impact of bilirubin on respiratory function and neurodevelopment of respiratory control in preterm infants using the Gunn rat model of preterm hyperbilirubinemia. Design/Methods: On postnatal day (P) 5, heterozygous (Nj) and jj Gunn rat pups were treated intraperitoneally with 200 mg/kg SDMX or an equivalent volume of saline. On P20, the animals underwent whole-body plethysmography to assess disturbances in the HVR (10% O2, 5 minutes) and HCVR (5% CO2, 5 minutes). Results: Both males and females in the jj SDMX group showed blunted HVR of 1.31 mL/g/min and 1.51 mL/g/min in comparison to the jj saline group (1.59 mL/g/min and 1.85 mL/g/mL respectively) (p < 0.05, t test; Fig. 1). In contrast, there was no effect of SDMX on the HCVR of either male or female rats.
Conclusion(s): The results suggest that neonatal exposure to bilirubin has long term implications for ventilatory defense response to hypoxia later in life. Further studies are needed to investigate the neural consequences of hyperbilirubinemia in former preterm infants.
