Ann Thorac Surg 2002;73:129-130
© 2002 The Society of Thoracic Surgeons
Invited commentary
Philippe Menasché, MD, PhDa
a Department of Cardiovascular Surgery, Hôpital Bichat, 46 rue Henri-Huchard, 75018 Paris, France
e-mail: ccv-bloc.sec3{at}bch.ap-hop-paris.fr
The growing development of off-pump coronary artery bypass surgery has generated a rekindled interest in the means of reducing the invasiveness of cardiopulmonary bypass (CPB) and, more specifically, the adverse events related to the generalized inflammatory response triggered by extracorporeal circulation. This response results from the complex interplay of multiple cascades among which a pivotal role is played by neutrophil activation. However, whereas most studies have focused on the magnitude or the intraoperative time course of neutrophil activation, few have addressed the issue of the delayed effects of this phenomenon. The study by Dr Chello and associates brings up the original hypothesis that cytokines (primarily interleukin 8) liberated during CPB reduce neutrophil apoptosis, thereby suggesting that the resulting prolongation of their survival could account for some delayed postoperative neutrophil-mediated adverse events. To reach this conclusion, the authors have compared neutrophils from patients undergoing CPB with those collected during off-pump operations and in normal control subjects. In addition to measuring circulating levels of various cytokines and adhesion molecule (CD11b) expression, neutrophil apoptosis has been assessed on morphologic and biochemical end points. Of particular interest is the finding that CPB significantly reduces caspase activity, which identifies a potential mechanism by which neutrophil apoptosis is inhibited.
Although evidence for neutrophil apoptosis was primarily derived from in vitro experiments and as such cannot be readily extrapolated to the clinical setting, this carefully designed and executed study is important for at least two reasons. First, from a cognitive standpoint, it improves our understanding of the pathophysiology of neutrophil-mediated damage following CPB by emphasizing the potential role of inhibited apoptosis. In particular, it is noteworthy that surgical stress by itself can reduce neutrophil apoptosis, as demonstrated in the off-pump group, and consequently potentiate inflammatory tissue damage, thereby explaining why it is oversimplistic to anticipate the abrogation of this form of damage from the sole elimination of CPB. Second, from a practical standpoint, the results of this study identify apoptosis as a potential target for interventions designed to mitigate the inflammatory response to bypass. Although the biochemical data suggestive of inhibited apoptosis were not correlated with markers for neutrophil-related damage (like production of oxygen free radicals or proteolytic enzymes) or clinically relevant adverse events, one can speculate that reestablishing normal patterns of neutrophil apoptosis would shorten their life span and consequently restrict the time period during which they can exert their tissue-damaging effects. So far, most strategies targeted at reducing the inflammatory response to CPB have focused on limitation of neutrophil activation. This objective is difficult to achieve because of the multiplicity and redundancy of the pathways involved in this activation. The present study suggests that enhancement of neutrophil apoptosis might be an alternate means of blunting postbypass inflammatory injury, provided it can be demonstrated that this strategy is not plagued with specific detrimental effects such as a reduced defense against infections.
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Inhibition of neutrophil apoptosis after coronary bypass operation with cardiopulmonary bypass
- Massimo Chello, Pasquale Mastroroberto, Angela Quirino, Giovanni Cuda, Francesco Perticone, Francesco Cirillo, and Elvio Covino
Ann. Thorac. Surg. 2002 73: 123-129.
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