Cardiopulmonary bypass in the newborn: effects of circulatory cell-free hemoglobin and hyperoxia evaluated in a novel rat pup model
Jungner, Åsa LU ; Vallius Kvist, Suvi LU ; Bruschettini, Matteo LU
; Romantsik, Olga
LU
; Gram, Magnus
LU
and Ley, David
LU
(2017)
In Intensive Care Medicine Experimental
5(1).
- Abstract
- Background: Infants with congenital heart defects (CHD) are at risk for white matter brain injury. This novel rat pup model characterizes the systemic effects of intravasal cell-free hemoglobin and hyperoxia, hypothesizing that immature endogenous scavenging systems relate to increased vulnerability to conditions present during cardiopulmonary bypass (CPB).
Methods: Plasma pharmacokinetics of cell-free human hemoglobin (Hb) was determined after intraperitoneal (i.p.) administration in postnatal day 6 (P6) rat pups. Cell-free hemoglobin degradation, scavenger- and oxidative stress responses in altered oxygen environments were evaluated in P6 rat pups exposed to i.p. cell-free Hb or vehicle and subjected to hyperoxia or normoxia for 24... (More) - Background: Infants with congenital heart defects (CHD) are at risk for white matter brain injury. This novel rat pup model characterizes the systemic effects of intravasal cell-free hemoglobin and hyperoxia, hypothesizing that immature endogenous scavenging systems relate to increased vulnerability to conditions present during cardiopulmonary bypass (CPB).
Methods: Plasma pharmacokinetics of cell-free human hemoglobin (Hb) was determined after intraperitoneal (i.p.) administration in postnatal day 6 (P6) rat pups. Cell-free hemoglobin degradation, scavenger- and oxidative stress responses in altered oxygen environments were evaluated in P6 rat pups exposed to i.p. cell-free Hb or vehicle and subjected to hyperoxia or normoxia for 24 h. Plasma and liver were analyzed for free heme, haptoglobin, hemopexin, heme-oxygenase 1, and 8-OHdG at 3–120 h post-injection. Baseline scavenging properties were evaluated in P0-P12 rat pups.
Results: Cell-free Hb displayed peak plasma concentrations of 3.6 ± 0.5 mg/mL (mean ± SD) at 3 h post-administration. Animals exposed to cell-free Hb demonstrated a 30-fold increase in plasma haptoglobin and a decrease in plasma hemopexin to 1/6 of concentrations observed in pups exposed to vehicle. Exposure to cell-free Hb and hyperoxia mediated increased plasma concentrations of free heme (72.7 ± 19.5 μM, mean ± SD) compared to exposure to cell-free Hb and normoxia (49.3 ± 13.1 μM) at 3 h, and an elevated hepatic mRNA expression of heme-oxygenase 1. mRNA expression of haptoglobin and hemopexin was increased in animals exposed to hemoglobin with a mitigated response in pups exposed to hemoglobin and hyperoxia. Animals exposed to hyperoxia displayed an increase in hepatic transcription of scavenger proteins at 24 h. Combined exposure to cell-free Hb and hyperoxia mediated an increased DNA- oxidation at 6 h, whereas all insults conveyed a decrease in DNA-oxidation at 120 h.
Conclusions: In this study, we present a novel rat pup model with scavenging characteristics and brain maturation similar to newborns with CHD. We have confirmed a distinct scavenger response after exposure to systemic cell-free hemoglobin. We have indications of an accelerated metabolism of cell-free Hb and of an altered transcription of scavenger proteins in a hyperoxic environment. We believe that this model will prove valuable in future delineation of inflammatory and oxidative end-organ damage following CPB.
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Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/73b3fb76-1318-49db-a424-d5a9102917be
- author
- Jungner, Åsa
LU
; Vallius Kvist, Suvi
LU
; Bruschettini, Matteo
LU
; Romantsik, Olga
LU
; Gram, Magnus
LU
and Ley, David
LU
- organization
- publishing date
- 2017
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Intensive Care Medicine Experimental
- volume
- 5
- issue
- 1
- article number
- 45
- publisher
- Springer
- external identifiers
-
- pmid:28980221
- scopus:85063005595
- ISSN
- 2197-425X
- DOI
- 10.1186/s40635-017-0153-2
- language
- English
- LU publication?
- yes
- id
- 73b3fb76-1318-49db-a424-d5a9102917be
- date added to LUP
- 2020-11-19 11:39:34
- date last changed
- 2024-04-19 19:01:55
@article{73b3fb76-1318-49db-a424-d5a9102917be,
abstract = {{Background: Infants with congenital heart defects (CHD) are at risk for white matter brain injury. This novel rat pup model characterizes the systemic effects of intravasal cell-free hemoglobin and hyperoxia, hypothesizing that immature endogenous scavenging systems relate to increased vulnerability to conditions present during cardiopulmonary bypass (CPB).<br/>Methods: Plasma pharmacokinetics of cell-free human hemoglobin (Hb) was determined after intraperitoneal (i.p.) administration in postnatal day 6 (P6) rat pups. Cell-free hemoglobin degradation, scavenger- and oxidative stress responses in altered oxygen environments were evaluated in P6 rat pups exposed to i.p. cell-free Hb or vehicle and subjected to hyperoxia or normoxia for 24 h. Plasma and liver were analyzed for free heme, haptoglobin, hemopexin, heme-oxygenase 1, and 8-OHdG at 3–120 h post-injection. Baseline scavenging properties were evaluated in P0-P12 rat pups.<br/>Results: Cell-free Hb displayed peak plasma concentrations of 3.6 ± 0.5 mg/mL (mean ± SD) at 3 h post-administration. Animals exposed to cell-free Hb demonstrated a 30-fold increase in plasma haptoglobin and a decrease in plasma hemopexin to 1/6 of concentrations observed in pups exposed to vehicle. Exposure to cell-free Hb and hyperoxia mediated increased plasma concentrations of free heme (72.7 ± 19.5 μM, mean ± SD) compared to exposure to cell-free Hb and normoxia (49.3 ± 13.1 μM) at 3 h, and an elevated hepatic mRNA expression of heme-oxygenase 1. mRNA expression of haptoglobin and hemopexin was increased in animals exposed to hemoglobin with a mitigated response in pups exposed to hemoglobin and hyperoxia. Animals exposed to hyperoxia displayed an increase in hepatic transcription of scavenger proteins at 24 h. Combined exposure to cell-free Hb and hyperoxia mediated an increased DNA- oxidation at 6 h, whereas all insults conveyed a decrease in DNA-oxidation at 120 h.<br/>Conclusions: In this study, we present a novel rat pup model with scavenging characteristics and brain maturation similar to newborns with CHD. We have confirmed a distinct scavenger response after exposure to systemic cell-free hemoglobin. We have indications of an accelerated metabolism of cell-free Hb and of an altered transcription of scavenger proteins in a hyperoxic environment. We believe that this model will prove valuable in future delineation of inflammatory and oxidative end-organ damage following CPB.<br/>}},
author = {{Jungner, Åsa and Vallius Kvist, Suvi and Bruschettini, Matteo and Romantsik, Olga and Gram, Magnus and Ley, David}},
issn = {{2197-425X}},
language = {{eng}},
number = {{1}},
publisher = {{Springer}},
series = {{Intensive Care Medicine Experimental}},
title = {{Cardiopulmonary bypass in the newborn: effects of circulatory cell-free hemoglobin and hyperoxia evaluated in a novel rat pup model}},
url = {{http://dx.doi.org/10.1186/s40635-017-0153-2}},
doi = {{10.1186/s40635-017-0153-2}},
volume = {{5}},
year = {{2017}},
}