Acute adrenal cortex injury during cardiopulmonary bypass in a canine model.

Abstract

OBJECTIVE: Cardiopulmonary bypass (CPB) might induce systemic inflammatory responses that cause acute injuries to multiple organs. However, no direct evidence exists to determine whether CPB leads to adrenal cortex injury or to describe its underlying mechanism. METHODS: Twelve healthy adult beagles were randomly assigned into control and CPB groups. After cannulation, mild hypothermia CPB was performed in the CPB group but not in the control group. The serum concentrations of various cytokines, cortisol, and aldosterone were assessed. Adrenal cortex injuries were evaluated using standard histological methods. Steroidogenic enzymes and the nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome pathway were detected using quantitative polymerase chain reaction and Western blot analysis. RESULTS: During CPB, serum interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor α, cortisol, and aldosterone levels were significantly higher in the CPB group. The pathologic study revealed higher injury scores (3.6 ± 0.6 vs 0.7 ± 0.7) and significantly more severe edema, inflammatory cell infiltration (lymphocytes and neutrophils), and apoptosis in the CPB group. The electron microscopic examination showed swollen mitochondria, ruptured mitochondrial cristae, reduced lipid droplets, and increased secondary lysosomes in the CPB group. The mRNA expression levels of NLRP3 and the protein levels of 17α-hydroxylase and IL-1β in adrenal tissue were significantly upregulated in the CPB group. CONCLUSIONS: CPB induces significant systemic and local inflammation in the adrenal cortex and results in cytological architectural and ultrastructural alterations in adrenocorticocytes. In addition, the NLRP3 inflammasome pathway might promote adrenal gland injury during CPB and might represent a novel potential therapeutic target.