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Pathophysiology of extracellular haemoglobin : use of animal models to translate molecular mechanisms into clinical significance

Smeds, Emanuel LU ; Romantsik, Olga LU ; Jungner, Åsa LU ; Erlandsson, Lena LU and Gram, Magnus LU (2017) In ISBT Science Series 12(1). p.134-141
Abstract
The blood's major gas exchange is carried out by haemoglobin, a haeme protein that binds iron and oxygen and can have potentially dangerous side-effects due to redox reactions. Haemoglobin is a very abundant molecule with a concentration of 150 g/l in whole blood, resulting in almost one kg haemoglobin in an adult human body. Normal turnover of red blood cells results in significant haemoglobin release, and pathological conditions that involve haemolysis can lead to massive haemoglobin levels. To control for the potential threat of extracellular haemoglobin, several protective defence systems have evolved. Many pathological conditions, diseases as well as iatrogenic conditions, such as infusion of haemoglobin-based oxygen carriers,... (More)
The blood's major gas exchange is carried out by haemoglobin, a haeme protein that binds iron and oxygen and can have potentially dangerous side-effects due to redox reactions. Haemoglobin is a very abundant molecule with a concentration of 150 g/l in whole blood, resulting in almost one kg haemoglobin in an adult human body. Normal turnover of red blood cells results in significant haemoglobin release, and pathological conditions that involve haemolysis can lead to massive haemoglobin levels. To control for the potential threat of extracellular haemoglobin, several protective defence systems have evolved. Many pathological conditions, diseases as well as iatrogenic conditions, such as infusion of haemoglobin-based oxygen carriers, cerebral intraventricular haemorrhage, extracorporeal circulation and the pregnancy complication pre-eclampsia, involve abnormal levels of haemolysis and extracellular haemoglobin. Although quite different aetiology, the haemoglobin-induced damage often causes similar clinical sequelae and symptoms. Here, we will give an overview of the pathophysiological mechanisms of extracellular haemoglobin and its metabolites. Furthermore, we will highlight the use of animal models in advancing the understanding of these mechanisms and discuss how to utilize the knowledge in the development of new and better pharmaceutical therapies.
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Animal models, Extracellular hemoglobin, Hemolysis, Organ damage, Therapeutics, Toxicity
in
ISBT Science Series
volume
12
issue
1
pages
8 pages
ISSN
1751-2824
DOI
10.1111/voxs.12328
language
English
LU publication?
yes
id
ac002612-e16f-4c3a-9335-e6901ca0b0de
date added to LUP
2017-02-22 22:21:14
date last changed
2017-07-26 08:11:30
@article{ac002612-e16f-4c3a-9335-e6901ca0b0de,
  abstract     = {The blood's major gas exchange is carried out by haemoglobin, a haeme protein that binds iron and oxygen and can have potentially dangerous side-effects due to redox reactions. Haemoglobin is a very abundant molecule with a concentration of 150 g/l in whole blood, resulting in almost one kg haemoglobin in an adult human body. Normal turnover of red blood cells results in significant haemoglobin release, and pathological conditions that involve haemolysis can lead to massive haemoglobin levels. To control for the potential threat of extracellular haemoglobin, several protective defence systems have evolved. Many pathological conditions, diseases as well as iatrogenic conditions, such as infusion of haemoglobin-based oxygen carriers, cerebral intraventricular haemorrhage, extracorporeal circulation and the pregnancy complication pre-eclampsia, involve abnormal levels of haemolysis and extracellular haemoglobin. Although quite different aetiology, the haemoglobin-induced damage often causes similar clinical sequelae and symptoms. Here, we will give an overview of the pathophysiological mechanisms of extracellular haemoglobin and its metabolites. Furthermore, we will highlight the use of animal models in advancing the understanding of these mechanisms and discuss how to utilize the knowledge in the development of new and better pharmaceutical therapies.<br/>},
  author       = {Smeds, Emanuel and Romantsik, Olga and Jungner, Åsa and Erlandsson, Lena and Gram, Magnus},
  issn         = {1751-2824},
  keyword      = {Animal models,Extracellular hemoglobin,Hemolysis,Organ damage,Therapeutics,Toxicity},
  language     = {eng},
  number       = {1},
  pages        = {134--141},
  series       = {ISBT Science Series},
  title        = {Pathophysiology of extracellular haemoglobin : use of animal models to translate molecular mechanisms into clinical significance},
  url          = {http://dx.doi.org/10.1111/voxs.12328},
  volume       = {12},
  year         = {2017},
}