Circulating neutrophils exhibit enhanced apoptosis associated with mitochondrial dysfunctions after surgery under general anaesthesia

Background: Evidence suggests that apoptosis plays a main role in the posto perative changes detected in the polymorphonuclear neutrophil (PMN) populat ion. Furthermore, recent studies have demonstrated that mitochondrial alter ations constitute critical events of the apoptotic cascade. In this study w e investigated whether apoptosis among neutrophils taken from patients unde rgoing surgical trauma could be associated with perturbation of mitochondri al transmembrane potential (Delta Psi (m)) and/or exaggerated production of mitochondrial reactive oxygen species (ROS). Methods: Twenty-seven patients undergoing elective surgery under general an aesthesia were enrolled in the study. Peripheral blood samples were drawn o ne day before the operation and at 12 and 24 h after surgery. Apoptosis rat e was assessed by staining neutrophils with 7-amino-actinomycin D (7-AAD) a nd by analysis by a FACScan flow cytometer. In order to evaluate Delta Psi (m), cells were exposed to 3,3-dihexyloxacarbocyanine iodide [DiOC(6)(3)]; intracellular ROS was measured by means of hydroethidine (HE) and 2,7-diclo rofluorescein diacetate (DCFH-DA), followed by analysis on a cytofluoromete r. Results: At 12 h following surgery we observed a significantly (P < 0.05) i ncreased frequency of apoptotic PMNs compared to that preoperatively (30.79 +/- 3.68% vs 7.40 +/- 0.69%). At this same time-point, the rate of neutrop hils stained with HE, DCFH-DA and [DiOC(6)(3)] were significantly (P < 0.05 ) higher compared to baseline (51.05 +/- 5.44%, 50.58 +/- 5.84% and 55.31 /- 4.33% vs 20.17 +/- 2.38%, 19.59 +/- 2.03 and 25.43 +/- 2.71% respectivel y). Overall measurements returned to the preoperative values 24 h after sur gery Conclusion: These data suggest that surgery under general anaesthesia trigg ers in the immediate postoperative period pathways of PMN accelerated apopt osis associated with significant alterations in mitochondrial function.