The influence of cardiopulmonary bypass on cytokines and cell-cell communication

Cardiopulmonary bypass (CPB) is characterized by systemic endotoxemia immediately after its onset as well as the systemic release of proinflammatory cytokines, including tumor necrosis factor-alpha and the interleukins 1 and 6. Recent studies document that increased morbidity and mortality rates correlate with elevated systemic concentrations of these proinflammatory cytokines during adult and neonatal sepsis, following thoracoabdominal aortic aneurysm repair, as well as following CPB. These proinflammatory cytokines induce increased neutrophil and endothelial surface adhesive molecule expression, thereby promoting enhanced neutrophil-endothelial adherence. Increased neutrophil-endothelial adherence and subsequent neutrophil organ binding are thought to be a "final common pathway" of organ injury during clinical inflammatory conditions. Proinflammatory cytokines also increase cellular expression of inducible nitric oxide synthase, thus increasing cellular production of nitric oxide, a known inflammatory mediator. This review discusses recent evidence of the adverse effects of proinflammatory cytokine release during CPB and therapeutic modalities that can reduce the systemic concentrations of these mediators of inflammation.