Inflammatory Cytokine Profiles in 24-Hour Brain Stem Death Model

Boon, AC; Hoe, LE See; Pederson, SE; Obonyo, NG; Wells, MA; Bartnikowski, NJ; Passmore, MR; Marshall, L; James, L; Tung, J; Suen, JY; Macdonald, PS; McGiffin, DC; Fraser, JF

doi:10.1016/j.healun.2018.01.506

Author(s)

Boon, AC

Hoe, LE See

Pederson, SE

Obonyo, NG

Wells, MA

Bartnikowski, NJ

Passmore, MR

Marshall, L

James, L

Tung, J

Suen, JY

Macdonald, PS

McGiffin, DC

Fraser, JF

Griffith University Author(s)

Fraser, John F.

Wells, Matt A.

Year published

2018

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Abstract

Purpose The main factor limiting transplantation is the availability of suitable donated organs from brain stem death (BSD) donors. BSD induces organ damage, potentially via inflammatory response which influences the organs quality and results in poor organ functions in the recipient. A clinically relevant 24-hour, ovine model of BSD could be used to investigate the inflammatory response which may reduce deleterious inflammation that occurs in BSD and transplantable organs. Therefore, we aimed to Methods Six healthy female sheep were randomized into BSD and Sham control (n=3 per group). Sheep were anesthetized and mechanically ...
View more >Purpose The main factor limiting transplantation is the availability of suitable donated organs from brain stem death (BSD) donors. BSD induces organ damage, potentially via inflammatory response which influences the organs quality and results in poor organ functions in the recipient. A clinically relevant 24-hour, ovine model of BSD could be used to investigate the inflammatory response which may reduce deleterious inflammation that occurs in BSD and transplantable organs. Therefore, we aimed to Methods Six healthy female sheep were randomized into BSD and Sham control (n=3 per group). Sheep were anesthetized and mechanically ventilated prior to undergoing BSD induction by inflation of an extradural catheter, and sheep were monitored in an intensive care unit environment for 24 hours. Our group has validated the antibodies and developed ELISA assay for sheep cytokines. Cytokines (interleukin(IL)-1β, 6, 8 and tumor necrosis factor-α) were measured in plasma and BAL. Blood and BAL samples were Results Circulating plasma IL-6 concentrations were elevated during the period of BSD, with significantly (P<0.01) increased by 74% at 2 hour post-BSD when compared to controls. Increased of IL-8 concentrations were observed in BSD plasma and BAL at early time points. There was no difference in plasma and BAL IL-1β and TNF-α concentrations between the groups. White blood cell (WBC) count increased during the period of BSD, with signicantly (P<0.05) increased numbers of circulating neutrophil cells in Conclusion This is the first report to demonstrate the inflammatory cytokine profiles in a 24 hour ovine model of BSD. BSD contributes to increased circulating neutrophils in the blood and neutrophil infiltration in the lung which could further contribute to systemic inflammation and lung dysfunctions. The development of this model will allow further investigation of novel therapies seeking to augment the effects of inflammation and organs injury induced by BSD.
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