University of Groningen Brain death and organ donation Hoeksma, Dane

Brain death and organ donation

Hoeksma, Dane

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Publication date:

2017

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Citation for published version (APA):

Hoeksma, D. (2017). Brain death and organ donation: Observations and interventions. Rijksuniversiteit

Groningen.

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LIST OF ABBREVIATIONS

DCIP 2,6-dichloroindophenol

AKI Acute kidney injury

Paw Airway pressure

ALT Alanine transaminase

ADH Antidiuretic hormone

ASL Arterial spin labelling

AST Aspartate transaminase

AST Aspartate transaminase

BOLD Blood oxygen level dependent

BW Body weight

BSA Bovine serum albumin

BD Brain death

FCCP Carbonyl cyanide-4-(trifluoromethoxy) phenylhydrazone

CAT Catalase

CPP Cerebral perfusion pressure

Cxcl1 Chemokine ligand 1

Ccl2 Chemokine ligand 2

CK-MB Creatine kinase (myocardium)

CrC Creatinine clearance

Cinc1 Cytokine induced neutrophil chemoattractant1

DBD Deceased brain-dead

DCD Deceased circulatory death

DGF Delayed graft function

DGF Delayed graft function

DPBS Dulbecco’s phosphate-buffered saline

TE Echo time

ETC Electron transport chain

ETCO₂ End-tidal CO₂

EDTA Ethylenediaminetetraacetic acid

ECD Expanded critera donors

FAO Fatty acid oxidation

FOV Field of view

FiO₂ Fraction of inspired oxygen

FeNa Fractional sodium excretion

GPx Glutathione peroxidase

GR Glutathione reductase

GAPDH Glyceraldehyde 3-phosphate dehydrogenase

HO-1 Heme oxygenase 1

H2O2 Hydrogen Peroxide

HAES Hydroxethyl starch

IL-6 Interleukin 6

IL-10 Interleukin-10

IL-6 Interleukin-6

ICP Intracranial pressure

I-R Ischemia-reperfusion

IPK Isolated perfused kidney

LDH Lactate dehydrogenase

LDHA Lactate dehydrogenase A

LD Living donor

MRI Magnetic resonance imaging

MDA Malondialdehyde

MnTMPyP: Manganese(III) tetrakis(1-methyl-4-pyridyl)porphyrin

MAP Mean arterial pressure

MCP-1 Monocyte chemotactic protein 1

NAG N-acetyl- -D-glucosaminidase

NADPH nicotinamide adenine dinucleotide phosphate

NA Noradrenaline

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GSSG Oxidized glutathione

SaO₂ Oxygen saturation

PAS Periodic-Acid Schiff

PMSF Phenylmethylsulfonyl fluoride

PBS Phosphate buffered saline

Pfk-1 Phosphofructokinase-1

PMN Polymorphonuclear

PEEP Positive end expiratory pressure

PNF Primary non-function

P-P Probability-probabilty

Pc Pyruvate carboxylase

Pk Pyruvate kinase

ROS Reactive oxygen species

GSH Reduced glutathione

TR Repetition time

RCR Respiratory control ratio

Crs Serum creatinine

SD Standard deviation

SOD: Superoxide dismutase

SVR Systemic vascular resistance

TLDA TaqMan low density array

TBA Thiobarbituric acid

TGF- Transforming growth factor-beta

TCA Tricarboxylic acid

TNF-

α

TNF-

α

α

UCr Urinary creatinine

Vcam1 Vascular adhesion molecule 1

H₂O Water

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AUTHOR AFFILIATIONS

AC van Erp1 _{RA Rebolledo}1,12,13

H van Goor8 _{ZS Veldhuis}1

D Hoeksma1 _{J Wiersema-Buist}1

CMV Hottenrott1 _{JC Wolters}5,14

B Jespersen9,10 _{B Yard}3

1 - Department of Surgery, Groningen Transplant Center, University Medical Center Groningen, the Netherlands

2 - Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark

3 - Department of Medicine, Nephrology, Endocrinology, Diabetology, Rheumatology, Heidelberg University, Mannheim, Germany

4 - Faculty of Medical Sciences, Department of Epidemiology, University Medical Center Groningen, Groningen, The Netherlands

5 - Systems Biology Centre for Energy Metabolism and Ageing, University of Groningen, Groningen, the Netherlands.

6 - Department of Pediatrics, University Medical Center Groningen, Groningen, the Netherlands.

7 - Deparment of cardiothoracical surgery, University Medical Center Groningen, Groningen, the Netherlands

8 - Department of Pathology and Medical Biology, University Medical Center Groningen, Groningen, the Netherlands

9 - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. 10 - Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark 11 - MR Research Center, Clinical Institute, Aarhus University, Aarhus, Denmark. 12 - Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile,

Santiago, Chile.

13 - Department of Digestive Surgery, Faculty of Medicine. Pontificia Universidad Católica de Chile, Santiago, Chile.

14 - Department of Analytical Biochemistry, Research Institute of Pharmacy, University of Groningen, Groningen, The Netherlands.

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ACKNOWLEDGMENTS

I would like to start off by mentioning the first three guys I met when I just arrived in Groningen: Martijn Posthumus, Diederik van Korven, and Wouter aan de Stegge. Experiencing my first year in Groningen just would not have been the same without the three of you. You guys know what I mean! After having to have moved from Utrecht, the days spent with you guys made this transition to Groningen feel seamless. We became friends and made that year a true once in a life-time experience! Thinking about it and realizing those days are gone makes me sad! I love you guys!

Henri, or as they say these days: professor Leuvenink! The moment I stepped into your office I immediately knew I was in the right place! You have the ability to appeal to a wide variety of people which is something I really admire. Thanks for believing in me from the time I set foot in your office!

Pragmatic, charismatic, and sympathetic is how I would describe you professor van Goor. It’s these characteristics which drew me to you and I think the same holds true for many others! I really admire your work ethic and learned a great deal from you even though we only started working extensively together in the last year of my PhD!

Jacco Zwaagstra, as the head of the lab I really had to watch out for you! Not adhering to protocols and not wearing a lab-coat got me into trouble with you on a regular basis! However, this never stood in the way of a good friendship and I really enjoyed our talks, especially about travelling abroad!

Petra, to put it simple, you were indispensable throughout my PhD time! My first days in the lab were under your supervision as were some of my last! I never stopped learning from you. Your organizational and of course technical skills were essential for me and my experiments!

Suzanne, thanks for putting a smile on my face every time you were in the lab! Your soft-natured personality is something truly amazing! Thanks for helping me around the lab and with experiments every now and then!

Janneke, I think you have the most experience out of anyone in the lab! The passion and determination you bring to the job is admirable! Thanks for always helping me so swiftly with any histology work! I hope you have a great time in your new house!

Maxi & Rolando. Older than me, both of you were like mentors to me considering the amount of experience and “know how” you brought to the table. I was lucky enough to catch a ride on the train you guys were in! I learned a great deal from the both of you! Yves Bodar, like Rihanna said: we fell in love in a hopeless place! From early morning till evening, day in day out, we found ourselves in a small closed operation room amidst brain-dead rats!! Ironically, these days were the best of my research period and you were largely responsible for that! I am glad we developed a close friendship outside this “hopeless place” as well. Unfortunately, you will not be able to attend my defense as you will be in the States! I wish you all the luck in the world and hope to see you more often!

Professor J.L. Hillebrands, D.J. Reijngoud, and B. Yard, thanks for reading my thesis and approving it!

I would like to thank Jan Niesing for providing data and figures at the eleventh hour! Norbert Majenberg en Sonja Buisman. My beloved students! I know I learned a lot from supervising you and I hope you guys learned a thing or two from me! I enjoyed working together with the both of you!

Atta Rehman, in was in dire need of another oxidative stress outcome measurement and as a matter of chance there you were! Thanks for helping me with the lab work and the Indian food we enjoined on numerous occasions! I hope you and your family are doing well in Pakistan!

Danial, you are the kind of person that radiates warmth and openness, even in the middle of the night when we met in the lab! I knew I had a friend in you the first time we met! We should make that trip to Iran soon!

Anne Koning and Leon van Dullemen, I don’t know anyone who even closely resembles either of you! You are unique in both your own ways and I am glad I started (and finished!) my PhD project alongside you guys!

Office mates Dirk Bosch and Maarten Niebling, sitting in the office with you guys was a total experience! Getting pencil cases flown at my neck at a hundred miles an hour whilst listening to the worst music outweighed the fact that no work got done!

Thanks to everyone else from surgical research lab, Welmoet, Geert, Bo, Jeffrey, Michael, Douwe, Jelle, Ton, Valerie, Jan-binne, Peter, Dafna, Leonie and from other labs Vicenzo Terlizzi and Marc Seelen.

All other fellow medical students who made my medical and PhD career an unforgettable one: Catherine de Sonnaville, Ignas Houben, Ashling Stel, Moniek Wouters, Guy Metting van Rijn, Erik Heeg, Michiel van Basten-Batenburg, Thank you!

All members of the Masterraad, Manon Crull, Broes Vervliet, Bernard Vonck, Jorien van Dooren, thanks for the times we spent together!

My paranymphs Rik Mencke en Marc Kirschbaum. Rik, we got to know each other at the start of both our PhD’s. Even though you were working on a completely different topic, you knew all the details of mine due to the endless amount of questions I would ask you! If there was anyone I could ask for help any place, anywhere, anytime, it was you! You really saved me at moments! You are a person who is truly yourself and not afraid to show it which I admire very much! Marc, we got to know each other in the lab and it took some time before we became friends! Some things need to grow I guess! You’re the person that leaves an impression anywhere you go and likewise you did on me and the whole of my PhD period!

The guys from O.H.G.E (Utrecht), even though you guys were not directly involved in my research, you deserve a spot in here no less than anyone else. To put down in words what you guys have brought me is not possible and therefore will not be taken a shot at! Thank you!

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Friends from Deventer, Henry Ong, Mick Verhaaf and Shahroez Peraee, I’ve known you longer than anyone else mentioned above and wish to never lose you guys from my life! Lucas, my little brother, thank you for always being the calmer one between the two of us! I am real proud of you and hope everything works out for you the way you want!

Dear mom and dad, without you I would not be standing here today. I cannot thank you enough for the unconditional support you always gave and still give.

Dear Anne, the start off my research career had me library-bound and it’s where I first saw you! Since that day, I’ve felt increasingly inseparable from you! Six years together have brought difficult times and struggles but having experienced that and eventually surviving that together means everything to me! I love you!

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BIOGRAPHY

Dane was born on February 14th_{, 1988, in Durban, South Africa. After having been raised}

in South Africa, Germany, and Ivory Coast, Dane graduated from high school at the Etty Hillesum Lyceum in 2006 in Deventer, the Netherlands. He obtained a pre-medical degree from University College Utrecht after which he studied medical statistics for a year at the Radboud University in Nijmegen. He then started medical school in 2010 at the Rijksuniversiteit Groningen. During his medical studies, participation in the summer school “Transplantation” led to a research internship at the surgical laboratory under the supervision of professors H.G.D. Leuvenink and H. van Goor. He decided to prolong his research career and alternated this with his medical studies. Two years of full time research eventually led to this thesis.

For his medical studies, Dane was a medical intern at the University Medical Centre Groningen as wel as “Deventer Ziekenhuis” in his hometown. During this period, Dane served as the chairman of the commission “de Masterraad” which represents the student body of the medical school of the Rijksuniversiteit Groningen. He completed his medical degree with a final internship at the neurosurgical department at the University Medical Center Utrecht which is where he now works as a doctor.

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