Transcription Factor NFκB Expression and Postsurgical Organ Dysfunction

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Abstract
To examine the role of neutrophil NF kappa B activation in organ dysfunction after major surgery. NF kappa B is a transcription factor involved in the signal transduction of many stimuli that may participate in the pathogenesis of sepsis and resultant multiple organ dysfunction syndrome (MODS). It may therefore be a potential target for modulation in the reduction of postsurgical MODS. Twenty-five patients undergoing major vascular surgery (thoracoabdominal aortic aneurysm repair) were studied. Perioperative levels of neutrophil NF kappa B, CD11b, and glutathione were measured. In vitro inhibition experiments using NF kappa B inhibitors were also performed. No differences in clinical parameters were apparent before surgery between the patients who subsequently developed MODS and those who did not. However, there was a significant difference in preoperative levels of NF kappa B between the patients who developed postoperative organ dysfunction and those who did not. There was also a significant preoperative difference between patients who survived surgery and those who did not. Glutathione levels were reduced both in patients who developed MODS and those who did not at the onset of surgery. NF kappa B inhibitors suppressed patient plasma-stimulated NF kappa B activation in healthy neutrophils. Preoperative neutrophil NF kappa B status may be a marker of postoperative outcome after major surgery, and therapy aimed at attenuating neutrophil NF kappa B activation may reduce postoperative sepsis and organ dysfunction.