Reduced Expression of Systemic Proinflammatory Cytokines after Off-Pump versus Conventional Coronary Artery Bypass Grafting

Background: Both cardiopulmonary bypass (CPB) and operative trauma are associated with increased expression of proinflammatory cytokines. We assessed the relative contribution of CPB on activation of various proinflammatory cytokines in patients undergoing coronary revascularization by comparing them with patients receiving coronary artery bypass grafts using off-pump (OPCAB) techniques. Methods: Twenty-six patients were assigned to either the OPCAB procedure using a suction device and regular sternotomy (n = 13) or were treated conventionally using extracorporeal circulation, blood cardioplegia and hypothermic arrest (29 - 31°C; n = 13). C-reactive protein and systemic levels of TNF-α, TNF specific receptors Rp1 and Rp2, Interleukin-6 (IL-6) and soluble IL-2 receptors (sIL-2r) were assayed by ELISA or EIA. To account for systemic nitric oxide production, total nitrate/nitrite (NOx) was measured using the Griess reaction. Results: Coronary revascularization with CPB was associated with a significant expression increase in the TNF-system and sIL-2r when compared to the OPCAB patients. Although IL-6 expression did not differ between both groups, C-reactive protein levels were significantly lower in the OPCAB group. Moreover, systemic NOx levels as the stable end-product of nitric oxide were lower in the OPCAB group. Conclusions: The data of the present study indicate that, despite comparable surgical trauma, the OPCAB revascularization procedure without the use of CPB and cardioplegic arrest significantly reduces the systemic inflammatory response syndrome and early catecholamine requirement. This may contribute to improved organ function, subsequently resulting in improved postoperative recovery from surgical revascularization procedures, particularly in critically ill patients.

Key words:

OPCAB - Inflammation - Cytokines

References

• 1 Boyle E, Pohlman T, Johnson M. et al . Endothelial cell injury in cardiovascular surgery: The systemic inflammatory response.  Annals of Thoracic Surgery. 1997;  63 277-284
• 2 Kirklin J. Prospects for understanding and eliminating the deleterious effects of cardiopulmonary bypass.  Annals of Thoracic Surgery. 1991;  51 529-531
• 3 Kishimoto J, Akira S, Taga T. Interleukin-6 and its receptor: a paradigm for cytokines.  Science. 1992;  258 593-597
• 4 Bauman H, Gauldie J. The acute phase response.  Immunology Today. 1994;  15 74-80
• 5 Barton B, Jackson J. Protective role of interleukin 6 in the lipopolysaccharide-galactosamine septic shock model.  Infection and Immunity. 1993;  61 1496-1499
• 6 DeMeules J, Pigula F, Mueller M. et al . Tumor necrosis factor and cardiac function.  Journal of Trauma. 1992;  32 686-692
• 7 Philip R, Epstein E. Tumor necrosis factor as an immunomodulator and mediator of monocyte cytotoxicity induced by itself, gamma-interferon and interleukin-1.  Nature. 1986;  323 86-89
• 8 Whittington R, Faulds D. Interleukin-2: A review of its pharmacological properties and therapeutic use in patients with cancer.  Drugs. 1993;  46 446-451
• 9 Vilcek J, Palombella V, Henrekson-DeStefano D. et al . Fibroblast growth enhancing activity of tumor necrosis factor and its relationship to other polypeptide growth factors.  Journal of Experimental Medicine. 1986;  163 632-643
• 10 Frater-Scroeder M, Risau W, Hallmann R. et al . Tumor necrosis factor type alpha, a potent inhibitor of endothelial cell growth in vitro is angiogenic in vivo.  Journal of the National Academy of Science (USA). 1987;  84 5277-5281
• 11 Yoshizumi M, Perrella M, Burnett J. et al . Tumor necrosis factor downregulates an endothelial nitric oxide synthase mRNA by shortening its half-life.  Circulation Research. 1993;  73 205-209
• 12 Engelman D T, Watanabe M, Engelman R M. et al . Constitutive nitric oxide release is impaired after ischemia and reperfusion.  Journal of Thoracic and Cardiovascular Surgery. 1995;  110 1047-1053
• 13 Ferrari R, Bachetti T, Confortini R. et al . Tumor necrosis factor soluble receptors in patients with congestive heart failure.  Circulation. 1995;  92 1479-1486
• 14 Weis M, Wildhirt S, Schulze C. et al . Modulation of coronary vasomotor tone by cytokines in cardiac transplant recipients.  Transplantation. 1999;  68 1263-1267
• 15 Young J, Windsor N, Leidman N. The relationship of soluble interleukin-2 receptor levels to allograft arteriopathy after heart transplantation.  Journal of Heart and Lung Transplantation. 1992;  11 79-85
• 16 Schmand J, Ayala A, Chadry I. Effects of trauma, duration of hypotension, and resucitation regimen on cellular immunity after hemorrhagic shock.  Critical Care Medicine. 1994;  22 1076-1081
• 17 Cinat M, Waxman K, Vaziri N. et al . Soluble cytokine receptors and receptor antagonists are sequentially released after trauma.  The Journal of Trauma: Injury, Infection and Critical Care. 1995;  39 112-120
• 18 Biasucci L, Vitelli A, Liuzzo G. et al . Elevated levels of IL-6 in unstable angina.  Circulation. 1996;  94 874-879
• 19 Watson C, Whittaker S, Smith N. et al . IL-6 acts on endothelial cells to preferentially increase their adherence for lymphocytes.  Clinical and Experimental Immunology. 1996;  105 112-116
• 20 Xing Z, Gauldie J, Cox G. et al . IL-6 is an anti-inflammatory cytokine required for controlling local or systemic acute inflammatory responses.  Journal of Clinical Investigation. 1998;  101 311-320