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CARDIOVASCULAR ANESTHESIA

Tumor Necrosis Factor Gene Polymorphism Is Associated with Enhanced Systemic Inflammatory Response and Increased Cardiopulmonary Morbidity After Cardiac Surgery

Departments of Anesthesia and Intensive Care and Clinical Chemistry, Section of Molecular Biology, Sahlgrenska University Hospital, Göteborg, Sweden

Address correspondence and reprint requests to Sven-Erik Ricksten, MD, PhD, Department of Anesthesia and Intensive Care, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden. Address e-mail to sven-erik.ricksten{at}aniv.gu.se

Cardiopulmonary bypass induces a systemic inflammatory response characterized by alterations in cardiopulmonary function. Mediators for this morbidity are the cytokines tumor necrosis factor (TNF)- and interleukins. A genomic polymorphism within the TNF locus is associated with increased TNF- levels and high mortality in severe trauma and sepsis. We assessed the relationship of biallelic polymorphisms of the TNF locus in patients undergoing elective cardiac surgery to release of proinflammatory cytokines and cardiopulmonary morbidity. TNF genotypes, plasma concentrations of TNF-, interleukin-6, and cardiopulmonary morbidity were studied in 95 unselected, consecutive patients undergoing routine cardiac surgery. TNF genotypes were determined by the solid-phase minisequencing method. Patients homozygous for the TNFB2 allele (n = 42) displayed larger peak concentrations of TNF- (11.3 ± 1.3 versus 7.8 ± 0.7 pg/mL; P = 0.013) and interleukin-6 (153 ± 27 versus 87 ± 7 pg/mL; P = 0.010) when compared with patients homozygous or heterozygous for TNFB1 (n = 53). The TNFB2 homozygotes had a higher incidence of left ventricular dysfunction (31% versus 9%; P = 0.029; odds ratio 3.84 [95% confidence interval, 1.40–24.3]), postoperative pulmonary dysfunction (24% versus 6%; P = 0.016; odds ratio 5.21 [95% confidence interval, 1.49–18.3]), and a lower pulmonary oxygenation index (29 ± 1.9 versus 36.1 ± 1.8; P = 0.013). Patients homozygous for the TNFB2 allele may develop an enhanced systemic inflammatory response with an increased risk of cardiopulmonary morbidity after cardiac surgery.

IMPLICATIONS: The associations between tumor necrosis factor (TNF) gene polymorphism, plasma cytokines, and cardiopulmonary function after elective cardiac surgery were evaluated. Patients homozygous for the TNFB2 allele displayed larger concentrations of TNF- and interleukin-6 and had an increased risk of developing left ventricular and pulmonary dysfunction compared with TNFB1 homo- or heterozygotes.

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