Slow Induction of Brain Death Leads to Decreased Renal Function and Increased Hepatic Apoptosis in Rats

Overview

Journal J Transl Med

Publisher Biomed Central

Specialties Biomedical Engineering
General Medicine

Date 2016 May 20

PMID 27193126

Citations 13

Authors

Rolando A Rebolledo

Dane Hoeksma

Christina M V Hottenrott

Yves J L Bodar

Petra J Ottens

Janneka Wiersema-Buist

Henri G D Leuvenink

Affiliations

Soon will be listed here.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Citing Articles

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Comparison of acute kidney injury following brain death between male and female rats.

Armstrong-Jr R, Ricardo-da-Silva F, Vidal-Dos-Santos M, da Anunciacao L, Ottens P, Correia C Clinics (Sao Paulo). 2023; 78:100222.

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Immunomodulatory effects of thalidomide in an experimental brain death liver donor model.

Santana A, Andraus W, Silva F, Delle H, Pepineli R, de Moraes E Sci Rep. 2021; 11(1):19221.

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Rat donor lung quality deteriorates more after fast than slow brain death induction.

van Zanden J, Rebolledo R, Hoeksma D, Bubberman J, Burgerhof J, Breedijk A PLoS One. 2020; 15(11):e0242827.

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Metformin Preconditioning and Postconditioning to Reduce Ischemia Reperfusion Injury in an Isolated Ex Vivo Rat and Porcine Kidney Normothermic Machine Perfusion Model.

Huijink T, Venema L, Posma R, De Vries N, Westerkamp A, Ottens P Clin Transl Sci. 2020; 14(1):222-230.

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