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We have shown that increased production of nitrite by human vascular tissue in response to cytokines is associated with induction of iNOS as shown at the molecular and protein levels, and further supported by the presence of increased Ca(2+)-independent nitric oxide synthase activity following cytokine stimulation.

<P>Background: Coronary artery bypass grafting (CABG) surgery is associated with systemic inflammation. Activation of neutrophils is a crucial step in inflammation and results in neutrophil sequestration within the tissues. One of the potential advantages of performing off-pump coronary artery bypass (OPCAB) surgery is the attenuation of the systemic inflammatory response. This prospective randomized study compares neutrophil activation in patients undergoing OPCAB versus those undergoing CABG with cardiopulmonary bypass (CPB). </P><P>Methods: Twenty patients undergoing primary isolated CABG were randomly divided prospectively into 2 groups: 1 group underwent CABG with CPB, and the other group underwent OPCAB. Central venous blood samples were obtained before skin incision and at 15 minutes, 60 minutes, 2 hours, 5 hours, and 24 hours following the initiation of CPB or application of the stabilization device. Differential white cell counts were measured with routine laboratory techniques. CD11b surface expression on neutrophils was measured by flow cytometry. Interleukin 8 levels in the plasma were measured by enzyme-linked immunosorbent assays. </P><P>Results: The 2 groups were matched with respect to preoperative and operative characteristics. White cell and neutrophil counts rose in both groups following the operation but were significantly higher in the OPCAB group at 5 hours (P < .001 and P = .002, respectively). Interleukin 8 concentrations were significantly higher in the CPB group at 5 hours following the initiation of CPB (P = .034). CD11b levels were significantly higher in the CPB group at 60 minutes (P = .002). Conclusion: This prospective randomized study demonstrates that the activation of circulating neutrophils as measured by CD11b expression is lower following OPCAB than in CPB. Although OPCAB is associated with significantly higher neutrophil counts, these neutrophils exhibit fewer activation markers. The lower postoperative neutrophil counts occurring in the CPB group may be explained by the activation and consequent sequestration of the neutrophils in the CPB circuit and tissues.</P>

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