Coronary artery bypass grafting surgery is associated with immunoparalysis of monocytes and dendritic cells

Abstract

Abstract Background Exposure of patient blood to the bypass circuitry and re-perfusion of the heart at the end of coronary artery bypass grafting (CABG) is associated with activation of leucocytes, the complement cascade and cytokine secretion. Dendritic cells (DC) and monocytes are immunoregulatory cells that may be impacted by CABG contributing to an altered immune status. This study investigated changes in the DC and monocyte immune profile in CABG patients at 5 time-points: admission, peri-operative, ICU, day 3 (D3) and day 5 (D5). Methods At each time point, freshly collected whole blood from 50 CABG patients was used in an ex-vivo whole blood culture model. Lipopolysaccharide (LPS) was added in parallel to model an infectious complication. Expression of DC and monocyte co-stimulatory and adhesion molecules and production of intracellular inflammatory mediators was measured via flow cytometry. Results CABG resulted in significant perturbation of monocyte and DC responses. DC and monocytes were immunoparalysed as evidenced by failure to respond to LPS stimulation. Modulation of DC and monocyte costimulatory and adhesion molecule expression and inflammatory mediator production was associated with prolonged length of stay in intensive care and post-operative atrial fibrillation. While DC and monocyte expression of co-stimulatory and adhesion molecules recovered towards baseline by D5 post-surgery, their capacity to produce inflammatory mediators did not. Conclusions DC and monocyte responses were significantly impaired following CABG. Use of an ex-vivo model to assess immune competency of cardiac surgery patients may provide a tool for the early prediction of adverse outcomes.