title: Slow induction of brain death leads to decreased renal function and increased hepatic apoptosis in rats.
abstract: Donor brain death (BD) is an independent risk factor for graft survival in recipients. While in some patients BD results from a fast increase in intracranial pressure, usually associated with trauma, in others, intracranial pressure increases more slowly. The speed of intracranial pressure increase may be a possible risk factor for renal and hepatic graft dysfunction. This study aims to assess the effect of speed of BD induction on renal and hepatic injury markers.
  
  
  
  BD induction was performed in 64 mechanically ventilated male Fisher rats by inflating a 4.0F Fogarty catheter in the epidural space. Rats were observed for 0.5, 1, 2 or 4 h following BD induction. Slow induction was achieved by inflating the balloon-catheter at a speed of 0.015 ml/min until confirmation of BD. Fast induction was achieved by inflating the balloon at 0.45 ml/min for 1 min. Plasma, kidney and liver tissue were collected for analysis.
  
  
  
  Slow BD induction led to higher plasma creatinine at all time points compared to fast induction. Furthermore, slow induction led to increased renal mRNA expression of IL-6, and renal MDA values after 4 h of BD compared to fast induction. Hepatic mRNA expression of TNF-α, Bax/Bcl-2, and protein expression of caspase-3 was significantly higher due to slow induction after 4 h of BD compared to fast induction. PMN infiltration was not different between fast and slow induction in both renal and hepatic tissue.
  
  
  
  Slow induction of BD leads to poorer renal function compared to fast induction. Renal inflammatory and oxidative stress markers were increased. Liver function was not affected by speed of BD induction but hepatic inflammatory and apoptosis markers increased significantly due to slow induction compared to fast induction. These results provide initial proof that speed of BD induction influences detrimental renal and hepatic processes which could signify different donor management strategies for patients progressing to BD at different speeds.
authors.affiliation: Department of Surgery, University Medical Center Groningen, University of Groningen, CMC V, Y2144, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands. rareboll@uc.cl.|Physiopathology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile. rareboll@uc.cl.
authors.forename: Rolando A
authors.identifier: 0000-0003-3501-4042
authors.initials: RA
authors.lastname: Rebolledo
authors.affiliation: Department of Surgery, University Medical Center Groningen, University of Groningen, CMC V, Y2144, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
authors.forename: Dane
authors.initials: D
authors.lastname: Hoeksma
authors.affiliation: Department of Cardiothoracic Surgery, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Christina M V
authors.initials: CM
authors.lastname: Hottenrott
authors.affiliation: Department of Surgery, University Medical Center Groningen, University of Groningen, CMC V, Y2144, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
authors.forename: Yves J L
authors.initials: YJ
authors.lastname: Bodar
authors.affiliation: Department of Surgery, University Medical Center Groningen, University of Groningen, CMC V, Y2144, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
authors.forename: Petra J
authors.initials: PJ
authors.lastname: Ottens
authors.affiliation: Department of Surgery, University Medical Center Groningen, University of Groningen, CMC V, Y2144, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
authors.forename: Janneka
authors.initials: J
authors.lastname: Wiersema-Buist
authors.affiliation: Department of Surgery, University Medical Center Groningen, University of Groningen, CMC V, Y2144, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
authors.forename: Henri G D
authors.initials: HG
authors.lastname: Leuvenink
mesh_terms: D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D001926:Brain Death / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D053148:Caspase 3 / Q000378:metabolism; D005786:Gene Expression Regulation; D007249:Inflammation / Q000097:blood / Q000235:genetics / Q000473:pathology; D015850:Interleukin-6 / Q000235:genetics; D007668:Kidney / Q000503:physiopathology*; D007677:Kidney Function Tests; D008099:Liver / Q000473:pathology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D011916:Rats, Inbred F344; D060888:Real-Time Polymerase Chain Reaction; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D051028:bcl-2-Associated X Protein; D008315:Malondialdehyde; D053148:Caspase 3
keywords: Brain death; Kidney transplantation; Liver transplantation; Organ donation