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Giovanna Delogu, MD; Sonia Moretti, MD; Giuseppe Famularo, MD; Sonia Marcellini, MD; Gino Santini, PhD; Adriana Antonucci, MD; Maurizio Marandola, MD; Luciano Signore, MD

Arch Surg. 2001;136:1190-1196.

Background  Previous studies have shown that a profound suppression of immune function transiently occurs in patients who undergo surgery under general anesthesia. The decline in the absolute counts of peripheral blood lymphocytes constitutes a major factor accounting for this immune defect, and recent evidence indicates that apoptosis plays a crucial role in determining postsurgical lymphocytopenia.

Hypothesis  An altered oxidation-reduction status of mitochondria may contribute through apoptosis to the loss of lymphocytes following surgical trauma and general anesthesia.

Design  We studied 16 patients with American Society of Anesthesiologists' physical status I or II who underwent elective surgery under general anesthesia. The data were collected prospectively.

Setting  University hospital.

Main Outcome Measures  Samples of peripheral blood were drawn on the day before surgery and at 24 and 96 hours after the operation. Following lymphocyte isolation, the mitochondrial transmembrane potential was assessed by flow cytometry using 3,3'-dihexylocarbo-cyanine iodide, and stains with hydroethidine and 2'-7'-dichlorofluorescein diacetate were used to determine the generation of reactive oxygen species. The labeling of lymphocytes with monobromobimane was used to assess the presence of reduced glutathione.

Results  At 24 hours after surgery, we detected a significantly elevated frequency of peripheral blood lymphocytes (P = .002), which incorporated low levels of 3,3'-dihexylocarbo-cyanine iodide, compared with the preoperative period. At this same time point, the frequency of lymphocytes with the hydroethidine- and 2'-7'-dichlorofluorescein diacetate–positive phenotype was elevated compared with baseline levels. Conversely, at 24 hours after surgery, the frequency of cells that stained positive for glutathione was strongly decreased compared with preoperative values. Overall measurements returned to the baseline levels at 96 hours after surgery.

Conclusion  The strict association we observed between the overproduction of reactive oxygen species and the disruption of the mitochondrial transmembrane potential supports the view that alterations in mitochondrial energy metabolism, paralleled by the presence of a pro-oxidant oxidation-reduction status, could be involved in the accelerated apoptotic loss of lymphocytes following surgical trauma and general anesthesia.

From the Institute of Anesthesia and Intensive Care (Drs Delogu, Antonucci, Marandola, and Signore) and the Department of Infectious Diseases (Drs Moretti, Marcellini, and Santini), "La Sapienza" University, and the Department of Medical Sciences, San Camillo Hospital (Dr Famularo), Rome, Italy.

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