Ann Thorac Surg 2006;81:137-138
© 2006 The Society of Thoracic Surgeons
Original article: Cardiovascular
Invited commentary
Thomas Bilfinger, MD, ScD
Department of Surgery, SUNY at Stony Brook, HSC T19 Room 80, Stony Brook, NY 11794
(Email: tbilfinger{at}notes.cc.sunysb.edu).
Bittar and colleagues discuss whether the inflammatory response (particularly after coronary bypass operations) can be predicted by genetic phenotyping [1].
The bypass circuit (ie, blood foreign surface interface) causes an intense pro-inflammatory reaction. This response seems to be macrophage and endothelial-cell induced. The effect of tumor necrosis factor 
(TNF) by itself seems to be negative inotropic and pro-inflammatory. Some cytoprotective effects have been proposed as well. TNF acts pro-inflammatory by self amplification as well as by induction and expression of other pro-inflammatory cytokines. The myocardium constitutively expresses a low level of TNF. Although macrophages are activated at the blood foreign surface interface, an increase of myocardial TNF after ischemia and reperfusion has also been demonstrated. It is unclear if TNF gene expression and peptide synthesis occur during global ischemia. Hence, the source of TNF is multifactorial. It is intriguing to merge molecular genetics with molecular mechanisms of the systemic inflammatory response. However, the systemic inflammatory response involves a multitude of humeral and cellular mechanisms, and it would be an oversimplification to assume that one molecule is responsible for this very complex phenomenon.
Genetic polymorphism is defined as the presence of multiple alleles at a gene locus in appreciable frequencies in a population. The TNF gene is embedded within the class three major histocompatibility complex on the short arm of chromosome 6. Whether TNF gene polymorphism influences TNF expression in patients undergoing coronary artery bypass grafting with or without cardiopulmonary bypass has been the object of a number of studies. The results have been conflicting.
How can we explain these discrepancies? First when planning or reading one of these studies, the goal at the onset has to be kept in mind. To study gene polymorphism and its possible influence on outcome as a consequence of cardiopulmonary bypass is one topic. To study the influence of gene polymorphism with two treatment strategies (ie, on pump vs off pump) is a completely different question. A third issue may be if gene polymorphism has the same distribution in a diabetic population as in a nondiabetic population. Furthermore, attention has to be paid to which allele is being compared. The TNF gene contains a large number of alleles. As a clinical tool, genetic testing for the purpose of detecting which patients are at increased risk for postoperative complications is intriguing, but at present this is impractical for most of us. It is not clear at this time if TNF is the marker that has the greatest predictive value or if another cytokine or molecular marker or a combination has more predictive value. However, as a concept, it is very appealing and will allow us to improve patient outcomes in the future, be it by tailoring of therapy in order to avoid complications, or be it by earlier recognition of the latter.
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- Bittar MN, Carey JA, Barnard JB, et al. Tumor necrosis factor alpha influences the inflammatory response after coronary surgery Ann Thorac Surg 2006;81:132-138.[Abstract/Free Full Text]
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