Cardiopulmonary bypass-induced inflammation: Is it important?

The systemic endotoxemia that occurs with the institution of cardiopulmonary bypass (CPB) is a potent stimulus for the release of proinflammatory cytokines, including tumor necrosis factor-α {TNF-α), interleukin-1 (IL-1) and IL-6. Raised IL-6 levels have been reported to correlate with post-CPB left ventricular wall-motion abnormalities and myocardial ischemic episodes. Neutrophil-endothelial adhesion is strongly implicated in the inflammation and reperfusion injury that may follow a period of CPB, and organ injury is thought to be, in part, neutrophil mediated. The CD11b neutrophil integrin primarily responsible for endothelial binding is rapidly, permanently, and preferentially expressed on exposure to cytokines. The endothelial ligand intercellular adhesion molecule-1 is also upregulated by cytokine exposure. Nitric oxide (NO) synthesized by the vascular endothelium can inhibit neutrophil-endothelial adhesion by downregulating CD11b/CD18 receptor expression and inhibit platelet activation. The cytokines TNF-α, IL-1, and endotoxin can cause the induction of NO synthase and the release of large amounts of NO that may cause tissue injury. Various treatment strategies to reduce CPB-induced inflammation provide evidence to support the causal relationship between CPB-activated cytokine release, neutrophil activation, and stimulation of increased NO synthesis. The significant reductions in TNF-α and IL-6 levels with hemofiltration during CPB in children are associated with improved hemodynamics and early postoperative oxygenation. Acadesine can inhibit the upregulation of leukocyte CD11b adhesion receptors, and treatment in patients before and during surgery can reduce early cardiac death, myocardial infarction, and combined adverse cardiovascular outcomes. Recent data suggest that administration of the serine protease inhibitor aprotinin to patients undergoing myocardial revascularization with CPB can reduce TNF-α blood levels and blunt neutrophil CD11b upregulation. Preliminary data suggest that aprotinin can inhibit cytokine-induced nitric oxide synthase expression and subsequent NO production by murine bronchial epithelial cells. These effects may explain some of the reported antiinflammatory effects of the serine protease inhibitors.