Pathophysiology of extracellular haemoglobinuse of animal models to translate molecular mechanisms into clinical significance Smeds, Emanuel; Romantsik, Olga; Jungner, Åsa; Erlandsson, Lena; Gram, Magnus General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.
AbstractThe blood's major gas-exchange is carried out by haemoglobin, a heme-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 turn-over 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 preeclampsia, involve abnormal levels of haemolysis and extracellular haemoglobin. Although quite different aetiology, the haemoglobin-induced damage often cause 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.