Ann Thorac Surg 2007;83:152
© 2007 The Society of Thoracic Surgeons
Original Articles: Cardiovascular
Invited commentary
Knut Tore Lappegard, MD, PhD
Department of Medicine, Nordland Hospital, Bodoe, N-8092 Norway
(Email: knut.lappegard{at}nlsh.no).
Although advances in perioperative evaluation and treatment have made cardiopulmonary bypass (CPB) a fairly safe procedure, complications still occur, especially in high-risk patients. The inflammatory response elicited by CPB is a double-edged sword; it contributes in protecting the patient from infection, but it is also associated with renal, pulmonary, cardiac, and nervous system complications. As the complement system plays a key role in the inflammatory process induced by CPB, blocking complement activation could be one way of reducing complications associated with this procedure. However, so far clinical trials with complement inhibition have only shown limited effects on outcome [1], although high-risk patients may benefit more [2]. One possible explanation for this is that blocking complement activation at an early stage of the cascade will inhibit the formation of both potentially harmful anaphylatoxins, as well as terminal complement components with bactericidal properties.
In their present report, Rinder and coworkers [3], who for years have contributed with important results in this field, show that a specific C5a receptor antagonist (C5aRA) effectively inhibits some modes of leukocyte activation during simulated extracorporeal circulation, while leaving others unaffected. Furthermore, the C5aRA did not inhibit formation of the bactericidal terminal complement complex. In line with previous studies, their results show that there are differences both between cell types (eg, granulocytes vs monocytes) and within one cell type (eg, granulocyte elastase release vs interleukin-8 release) in regard to complement dependence. A limitation of the study is the rather low number of experiments. As the authors themselves admit, this introduces the possibility of type II statistical errors, and it may be appropriate to have this in mind when evaluating the results. Nevertheless, in vitro studies like the one presented here are important in preparing for clinical trials with more tailored and specific complement inhibition. Receptor antagonists and other small molecular inhibitors are of interest both in CPB as well as in other disease states associated with inappropriate complement activation.
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References
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- Shernan SK, Fitch JC, Nussmeier NA, et al. Impact of pexelizumab, an anti-C5 complement antibody, on total mortality and adverse cardiovascular outcomes in cardiac surgical patients undergoing cardiopulmonary bypass Ann Thorac Surg 2004;77:942-949.[Abstract/Free Full Text]
- Haverich A, Shernan SK, Levy JH, et al. Pexelizumab reduces death and myocardial infarction in higher risk cardiac surgical patients Ann Thorac Surg 2006;82:486-492.[Abstract/Free Full Text]
- Rinder CS, Smith MJ, Rinder HM, et al. Leukocyte effects of C5a-receptor blockade during simulated extracorporeal circulation Ann Thorac Surg 2007;83:146-152.[Abstract/Free Full Text]
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Leukocyte Effects of C5a-Receptor Blockade During Simulated Extracorporeal Circulation
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Ann. Thorac. Surg. 83: 146-152.
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