Cerebral cytokine expression after cardiac surgery with cardiopulmonary bypass

Objectives

Cerebral cell damage after cardiac surgery with cardiopulmonary bypass (CPB) could, at least in part, be due to inflammatory processes. Our study was intended to test the hypothesis that proinflammatory cytokines would be upregulated in the brain during CPB, and to identify the signaling pathways involved.

Methods

Fourteen young pigs were operated on with standardized CPB in either normothermia (n = 7) or moderate hypothermia (n = 7). Six hours after termination of CPB, forehead brain tissue was taken for detection of gene expression and synthesis of tumor necrosis factor (TNF)-α, IL-1β, IL-6, IL-10 and inducible nitric oxide synthase (iNOS) by competitive reverse transcription polymerase chain reaction and/or Western blot. Phosphorylation level of the inhibitory protein of nuclear factor-κB (IκB-α) was also measured by Western blot. Additional probes of hippocampus, cortex and middle brain were taken for standard histology.

Results

mRNA and protein levels of TNF-α, IL-1β and IL-6, as well as phosphorylated IκB-α, were detected in all animals, and iNOS in 10/14 animals. The anti-inflammatory cytokine IL-10 was not expressed in any of the animals. Histological alterations including mild edema and a few trapped lymphocytes were found in the different areas investigated. Results were not affected by temperature management during CPB.

Conclusions

In our model, cardiac surgery is related to upregulation of proinflammatory cytokines and iNOS in the brain. This synthesis involves the activation of the nuclear factor-κB pathway. In contrast to our previous observations in other organs, there is no anti-inflammatory reaction in the brain 6 hours after CPB. Proinflammatory cytokines could contribute toward damaging brain cells after cardiac surgery.