Ann Thorac Surg 2006;82:109
© 2006 The Society of Thoracic Surgeons
Original article: Cardiovascular
Invited commentary
Y. John Gu, MD, PhD
University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen, 9700 RB the Netherlands
(Email: y.j.gu{at}med.rug.nl).
A systemic inflammatory response encountered during and after cardiopulmonary bypass turns to a severe postoperative immunosuppression in cardiac surgical patients, leading to a tendency of infection and multiorgan dysfunction. This is the current understanding of one of the most severe clinical scenarios of the adverse effects of cardiopulmonary bypass known as "whole body inflammatory response." In the past, particularly since the early 1980s, mounting evidence has suggested that patients who require cardiopulmonary bypass for cardiac operations are always associated with increased blood activation as a result of contact of blood with large scale nonphysiologic foreign surfaces. This heart-lung machine associated insult, together with the existence of surgical trauma and other events, such as reperfusion injury and cardiotomy suction, induces a strong inflammatory response mediated largely by the complement cascade and polymorphonuclear leukocytes. Recently it has been realized that cardiopulmonary bypass generates not only a pro-inflammatory response but also an anti-inflammatory response, which involves mostly monocytes, macrophages, and lymphocytes. Ultimately, an over-stimulation of inflammation during an operation may predispose patients to immune depression after the operation.
Reduced postoperative synthesis of interferon (IFN)-gamma, along with depressed human leukocyte antigen (HLA)-DR expression on monocytes, has been observed in patients exposed to cardiopulmonary bypass. This study conducted by Franke and coworkers [1] once again confirms this postoperative immunosuppression phenomenon in cardiac surgical patients. All patients included in this study, either for coronary artery bypass grafting or for valve replacement, were the so called "low-risk" patients who had an average ejection fraction of 64% and who had no major organ dysfunction or any known inflammation and infection before operation. Remarkably they all had a severe postoperative deficiency in IFN-gamma synthesis as well as depression of HLA-DR expression on monocytes lasting for at least 5 days after the operation. Of more interest was their in vitro work, which demonstrated that adding the recombinant interleukin (IL)-12 to blood samples taken from cardiac surgical patients, either preoperatively or postoperatively, could increase the synthesis of IFN-gamma. These results, although found in a laboratory setting, suggest that immune modulation by stimulation of endogenous IFN-gamma can be one of the possibilities to combat postoperative immune depression in cardiac surgical patients.
What are the implications of these laboratory data? First, results of this study indicate that almost all patients undergoing cardiac operations with cardiopulmonary bypass presented with a vulnerable postoperative period of immune depression, even the low-risk patients. Second, a reduced postoperative immune depression, as represented by a defect postoperative IFN-gamma synthesis and depressed HLA-DR expression on monocytes, does not seem to be always associated with clinically relevant problems in low-risk patients. Third, therapeutic use of recombinant IL-12 can be an option regulating the immune response in patients after cardiac surgery. However, it may carry certain unknown risks for patients because the results from animal experiments have already indicated that severe systemic side effects may occur, as mentioned in the current article (see Reference 29).
Nevertheless we have learned from the past that patients tolerate themselves against a systemic inflammatory response. Similarly, a majority of them will have sufficient immune reserve to defend themselves against infection during the postoperative period. For high-risk patients who are susceptible to postoperative infection and multiorgan dysfunction, a prompt diagnosis of postoperative immune depression, followed by an appropriate therapy, should be of crucial importance.
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References
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- Franke A, Lante W, Kurig E, Zöller LG, Weinhold C, Markewitz A. Is interferon gamma suppression after cardiac surgery caused by a decreased interleukin-12 synthesis? Ann Thorac Surg 2006;82:103-109.[Abstract/Free Full Text]
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