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Ann Thorac Surg 2006;81:132-137
© 2006 The Society of Thoracic Surgeons

Original article: Cardiovascular

Tumor Necrosis Factor Alpha Influences the Inflammatory Response After Coronary Surgery

Mohamad N. Bittar, MD, MRCS a , * , John A. Carey, FRCS a , James B. Barnard, BS, MRCS a , Vera Pravica, MD a , b , Abdul K. Deiraniya, FRCS, FETCS a , Nizar Yonan, MD, FRCS a , Ian V. Hutchinson, PhD b

a Department of Cardiothoracic Surgery, South Manchester University Hospitals NHS Trust, Wythenshawe Hospital
b School of Biological Sciences, University of Manchester, Manchester, United Kingdom

Accepted for publication July 13, 2005.

* Address correspondence to Dr Bittar, Department of Cardiac Surgery, Wythenshawe Hospital, Southmoor Rd, Manchester M239LT, United Kingdom (Email: mbittar{at}doctors.org.uk).

BACKGROUND: A systemic inflammatory response is not uncommonly observed after coronary revascularization. Tumor necrosis factor alpha is one of a number of modulators of this response. A functional polymorphism within the TNF{alpha} gene at position G-308A has been associated with increased TNF{alpha} levels. The relationship between predicted TNF{alpha} genotype and circulating TNF{alpha} levels in patients undergoing coronary revascularization surgery has yet to be defined. We examined the relationship between TNF{alpha} G-308A polymorphism, TNF{alpha} postoperative levels, and clinical outcome after coronary revascularization surgery.

METHODS: We obtained DNA from 96 consecutive patients who underwent elective coronary revascularization. Patients were genotyped for TNF{alpha} G-308A polymorphism using sequence specific primer–polymerase chain reaction (SSP-PCR). Tumor necrosis factor alpha levels were measured on serum samples taken 3 hours postoperatively using enzyme-linked immunosorbent assay (ELISA).

RESULTS: The prevalence of AA, AG, and GG TNF{alpha}-308 genotype was 12%, 40%, and 48%, respectively. Patients homozygous for A had higher circulating levels of TNF{alpha} (p = 0.009). Higher levels of TNF{alpha} were significantly associated with prolonged intensive care unit stay (p = 0.008), increase usage of an inotropic agent (p = 0.024), increased mortality risk (p = 0.018), and diabetes (p = 0.019). These remained statistically significant after risk stratification.

CONCLUSIONS: Patients of the AA-308 TNF{alpha} genotype showed significantly higher TNF{alpha} plasma levels. Higher plasma levels of TNF{alpha} were associated with less favorable outcome after coronary revascularization surgery. It may prove useful to utilize TNF{alpha} serum levels as a marker for identifying high-risk patients in the future.




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