BRAIN DEATH From Inflammation to Metabolic Changes Rolando Rebolledo Acevedo ISBN: 978-94-6182-647-3 Copyright 2016 © Rolando Rebolledo All rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means without permission of the author. Layout and printing: Off Page, Amsterdam BRAIN Death: DEATH: FROM INFLAMMATION Brain From Inflammation TO METABOLIC CHANGES to Metabolic Changes PhD thesis PhD thesis to obtain the degree of PhD at the University of Groningen on the the authority to obtain degreeofofthe PhD at the Rector Magnificus E. Sterken University Prof. of Groningen authoritywith of the andoninthe accordance Rector Magnificus Prof. Sterken the decision by the College ofE.Deans. and in accordance with the decision by the College of Deans. This thesis will be defended in public on This thesis will be defended in public on Wednesday 6 January 2016 at 12.45 hours Wednesday 6 January 2016 at 12.45 hours by by Rolando Rebolledo Acevedo born on 17 April 1982 Rolando Rebolledo Acevedo in Santiago, Chili born on 17 April 1982 in Santiago, Chili SUPERVISORS Prof. H.G.D. Leuvenink Prof. P. Romanque Prof. B. Jespersen ASSESSMENT COMMITTEE Prof. A.J. Moshage Prof. G. van Dijk Prof. M. Arrese TABLE OF CONTENTS Chapter 1 Introduction9 Chapter 2 Prednisolone has a positive effect on the kidney but not on the liver of brain dead rats: a potential role in complement activation 25 Chapter 3 Steroid anti-inflammatory effects did not improve organ quality in Brain-dead Rats 45 Chapter 4 Anti-apoptotic effects of 3,3’, 5-triiodo-l-thyronine in the liver of brain dead rats 65 Chapter 5 Slow induction of brain death leads to decreased renal function and increased hepatic apoptosis in rats 85 Chapter 6 Metabolic Changes in Brain Dead Rats 109 Chapter 7 Non invasive assessment of tissue oxygenation and organ perfusion in Brain Dead Rats. 127 Chapter 8 Mitochondrial function in Brain Dead Rats 143 Chapter 9 Summary, conclusion and future perspectives 169 Nederlandse samenvatting 175 Resumen en Español 181 Acknowledgements187 To my life partners Ximena and Simón To Roberto Bolaños, chilean writer, who died waiting for a liver transplantation. ...los viajes, el sexo y los libros son caminos que no llevan a ninguna parte, y que sin embargo son caminos por los que hay que internarse y perderse para volverse a encontrar o para encontrar algo, lo que sea, un libro, un gesto, un objeto perdido, para encontrar cualquier cosa, tal vez un método, con suerte: lo nuevo, lo que siempre ha estado allí.