329 - Alterations in respiration in a Gunn rat model of neonatal jaundice

Sunday, April 30, 2023

3:30 PM – 6:00 PM ET

Poster Number: 329
Publication Number: 329.345

Nicholas C. Rickman, Case Western Reserve University School of Medicine, Shaker Heights, OH, United States; Catherine Mayer, Case Western Reserve University, Cleveland, OH, United States; Sergei Vatolin, Case Western Reserve University School of Medicine, Cleveland, OH, United States; Cansu Tokat, Case Western Reserve University School of Medicine, Shaker Heights, OH, United States; Mrinaj Janampalli, Case Western Reserve University School of Medicine, Cleveland, OH, United States; Peter M. MacFarlane, Case Wester Reserve University/Rainbow Babies & Children's Hospital, Cleveland, OH, United States; Cynthia F. Bearer, UH Rainbow Babies & Children's Hospital/Case Western Reserve University, Cleveland, OH, United States

Presenting Author(s)

NR

Nicholas C. Rickman, Bachelor's (he/him/his)

Research Assistant
Case Western Reserve University School of Medicine
Shaker Heights, Ohio, United States

Background: Bilirubin is a byproduct of hemoglobin breakdown. It is excreted after being catabolized under normal conditions. When not bound by albumin, bilirubin can cross the blood-brain barrier and cause neurotoxicity. In preterm infants, apnea of prematurity has been associated with hyperbilirubinemia. The homozygous Gunn rat (jj) lacks the enzyme uridine diphosphate-glucuronosyltransferase-1A1, which is needed to catabolize bilirubin. This animal strain has been used for mechanistic studies of hyperbilirubinemia in term infants. We have used this rat strain to emulate many aspects of hyperbilirubinemia observed in preterm human infants.

Objective: In this study, we used this model of preterm hyperbilirubinemia to investigate the impact of bilirubin on respiratory rate.

Design/Methods: Rat pups received a single intraperitoneal injection of sulfadimethoxine (SDMX), which displaces bilirubin from albumin and induces acute hyperbilirubinemia, or an equivalent volume of saline, on postnatal day (P) 5. Whole-body plethysmography was used 24 h later, on P6, to assess ventilatory responses to acute hypoxia (Hx) and hypercapnia (HC).

Results: Homozygous jj pups treated with SDMX showed reductions in respiratory rate (breaths/minute) compared to both SDMX and saline injected heterozygous (Nj) pups and to jj pups treated with saline, during baseline, Hx, and HC measurements.

Conclusion(s): These data suggest that baseline ventilatory function is altered by developmental exposure to bilirubin. They also suggest that important ventilatory defense responses to Hx and HC are impaired by bilirubin, and this may be associated with increased risk of later death. Future directions include further analysis of breathing parameters and sex differences, as well as investigations into the mechanism of impact by bilirubin.