Brain stem death induces pro-inflammatory cytokine production and cardiac dysfunction in sheep model

Walweel, Kafa; Boon, Ai-Ching; Hoe, Louise E. See; Obonyo, Nchafatso G.; Pedersen, Sanne; Diab, Sara; Passmore, Margaret; Hyslop, Kieran; Colombo, Sebastiano Maria; Bartnikowski, Nicole; Bouquet, Mahé; Wells, M.; Black, Debra; Pimenta, Leticia Pretti; Stevenson, A. K.; Bisht, Kavita; Skeggs, K.; Marshall, Liam E.; Prabhu, Ashwin; James, L.; Platts, D.; Macdonald, P.; McGiffin, David C.; Suen, Jacky Y.; Fraser, John F.

doi:10.1016/j.bj.2021.10.007

Cited by 5 publications

(1 citation statement)

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“…Experimental studies have reported an upregulation of cytokines after brain death (BD), [1][2][3] resulting in harmful effects on organs suitable for transplantation. [1,2,4,5] Our previous research has demonstrated that BD induces inflammation at levels similar to sepsis, which is known to cause significant organ damage. [6] Glucagon-like peptide-1 (GLP-1) is a hormone secreted by the intestinal epithelium L-cells in response to food.…”

Section: Introductionmentioning

confidence: 99%

Does liraglutide alleviate inflammation in brain-dead donors? A randomized clinical trial

Custódio,

Massutti,

da Igreja

et al. 2023

Liver Transplantation

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Brain death triggers an inflammatory cascade that damages organs before procurement, adversely affecting the quality of grafts. This randomized clinical trial aimed to compare the efficacy of liraglutide compared to placebo in attenuating brain death-induced inflammation, endoplasmic reticulum stress, and oxidative stress. We conducted a double-blinded, placebo-controlled, randomized clinical trial with brain-dead donors. Fifty brain-dead donors were randomized to receive subcutaneous liraglutide or placebo. The primary outcome was the reduction in IL-6 plasma levels. Secondary outcomes were changes in other plasma pro-inflammatory (IL-1β, interferon-γ, TNF) and anti-inflammatory cytokines (IL-10), expression of antiapoptotic (BCL2), endoplasmic reticulum stress markers (DDIT3/CHOP, HSPA5/BIP), and antioxidant (superoxide dismutase 2, uncoupling protein 2) genes, and expression TNF, DDIT3, and superoxide dismutase 2 proteins in liver biopsies. The liraglutide group showed lower cytokine levels compared to the placebo group during follow-up: Δ IL-6 (−28 [−182, 135] vs. 32 [−10.6, 70.7] pg/mL; p = 0.041) and Δ IL-10 (−0.01 [−2.2, 1.5] vs. 1.9 [−0.2, 6.1] pg/mL; p = 0.042), respectively. The administration of liraglutide did not significantly alter the expression of inflammatory, antiapoptotic, endoplasmic reticulum stress, or antioxidant genes in the liver tissue. Similar to gene expression, expressions of proteins in the liver were not affected by the administration of liraglutide. Treatment with liraglutide did not increase the organ recovery rate [OR = 1.2 (95% CI: 0.2–8.6), p = 0.82]. Liraglutide administration reduced IL-6 and prevented the increase of IL-10 plasma levels in brain-dead donors without affecting the expression of genes and proteins related to inflammation, apoptosis, endoplasmic reticulum stress, or oxidative stress.

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