The Changes and Effects of the Plasma Levels of Tumor Necrosis Factor after Coronary Artery Bypass Surgery with Cardiopulmonary Bypass


  • Feyzi Abacilar
  • Omer Faruk Dogan
  • Umit Duman
  • Ibrahim Ucar
  • Metin Demircin
  • Unsal Ersoy
  • Riza Dogan
  • Erkmen Boke



Background. Systemic inflammatory response after cardiopulmonary bypass (CPB) is thought to result from contact of cellular and humoral blood components with the synthetic material of the extracorporeal circulation system, leukocyte and endothelial activation caused by ischemia and reperfusion or endotoxins, or by surgical trauma. Proinflammatory cytokines, such as tumor necrosis factor (TNF)-?, interleukin (IL)-6, and IL-8, play an important role in the inflammatory processes after CPB and may induce cardiac and lung dysfunction. This study examined the association of the increased release of TNF-? with increased myocardial and lung injury after CPB and its effect on postoperative morbidity.

Methods. Twenty patients undergoing elective coronary artery bypass grafting (CABG) were included in the study. Four intervals of blood samples were obtaind and assayed for TNF-?, white blood cells, C-reactive protein, and erythrocyte sedimentation rate.

Results. All patients were similar with regards to preoperative and intraoperative characteristics, and clinical outcomes were comparable. Plasma levels of TNF-? rose more than 20 pg/mL during and after standard CPB in 13 patients (group 1), whereas the plasma levels were less than 20 pg/mL in the remaining 7 patients (group 2) after CPB. The patients of the first group had increased mediastinal bleeding and prolonged intubation time compared to the other group.

Conclusion. Cardiac surgery and CPB stimulate systemic inflammatory processes characterized clinically by changes in cardiovascular and pulmonary function. Significant morbidity is rare, but most patients undergoing CPB exhibit some degree of organ dysfunction due to activation of the inflammatory response. This study showed that there were no major clinical results of TNF-? and white blood cell level, C-reactive protein, and erythrocyte sedimentation rate after the operation, but in patients with a high level of TNF-? (more than 20 pg/mL), increased mediastinal bleeding and longer orotracheal intubation time was observed. A number of studies have shown the increase of TNF-? after open heart surgery; however, the specific level of TNF-? was first described as 20 pg/mL in this study.


Dietrich W, Spannagl M, Jochum M, et al. 1990. Influence of high-dose aprotinin treatment on blood loss and coagulation patterns in patients undergoing myocardial revascularization. Anesthesiology 73:1119-26.nDeng MC, Dasch B, Erren M, Möllhoff T, Scheld HH. 1996. Impact of left ventricular dysfunction on cytokines, hemodynamics, and outcome in bypass grafting. Ann Thorac Surg 62: 184-90.nElliot MJ. 1993. Ultrafiltration and modified ultrafiltration in pediatric open heart operations. Ann Thorac Surg 56:1518-22.nFong Y, Lowry SF. 1990. Tumor necrosis factor in the pathophysiology of infection and sepsis. Clin Immunol Immunopathol 55:157-70.nButler J, Rocker GM, Westaby S. 1993. Inflammatory response to cardiopulmonary bypass. Ann Thorac Surg 55:552-9.nBeutler B, Milsark IW, Cerami A. 1985. Cachectin/tumor necrosis factor: production, distribution, and metabolic fate in vivo. J Immunol 135:3972-7.nBrasil LA, Gomes WJ, Salomao R, Buffolo E. 1998. Inflammatory response after myocardial revascularization with or without cardiopulmonary bypass. Ann Thorac Surg 66:56-9.nButler J, Chong GL, Baigrie RJ, Pillai R, Westaby S, Rocker GM. 1992. Cytokine responses to cardiopulmonary bypass with membrane and bubble oxygenation. Ann Thorac Surg 53:833-8.nButler J, Pillai R, Rocker GM, Westaby S, Parker D, Shale DJ. 1993. Effect of cardiopulmonary bypass on systemic release of neutrophil elastase and tumor necrosis factor. J Thorac Cardiovasc Surg 105:25-30.nChenoweth DE, Cooper SW, Hugli TE, Stewart RW, Blackstone EH, Kirklin JW. 1981. Complement activation during cardiopulmonary bypass: evidence for generation of C3a and C5a anaphylatoxins. N Engl J Med 3 04:497-503.nAshraf S, Bhattacharya K, Tian Y, Watterson K. 1999. Cytokine and S100B levels in pediatric patients undergoing corrective cardiac surgery with or without total circulatory arrest. Eur Cardiothorac Surg 16:32-7.nBarnes A. 1998. Measurement of serum cytokines. Lancet 352:324-5.nBelhomme D, Peynet J, Florens E, et al. 2000. Is adenosine preconditioning truly cardioprotective in coronary artery bypass surgery? Ann Thorac Surg 70:590-4.nBellomo R. 1992. The cytokine network in the critically ill. Anaesth Intensive Care 20:288-302.nGu YJ, van Oeveren W, Akkerman C, Boonstra PW, Huyzen RJ, Wildevuur CRH. 1993. Heparin coated circuits reduce the inflammatory response to cardiopulmonary bypass. Ann Thorac Surg 55:917-22.nSchindler R, Gelfand JA, Dinarello CA. 1990. Recombinant C5a stimulates transcription rather than translation of interleukin-1 (IL-1) and tumor necrosis factor: translational signal provided by lipopolysaccharide or IL-1 itself. Blood 76:1631-8.nSchulz CM, Pritisanac A, Schutz A, et al. 2002. Effects of phospholipidcoated extracorporeal circuits on clinical outcome parameters and systemic inflammatory response in coronary artery bypass graft patients. Heart Surg Forum 6:47-52.nSpeziale G, Ruvolo G, Marino B. 1996. A role for nitric oxide in the vasoplegic syndrome. J Cardiovasc Surg (Torino) 37:301-3.nStarnes HF Jr, Warren RS, Jeevanandam M, et al. 1988. Tumor necrosis factor and the acute metabolic response to tissue injury in man. J Clin Invest 82:1321-5.nBergman MR, Holycross BJ. 1996. Pharmacological modulation of myocardial tumor necrosis factor-alpha production by phosphodiesterase inhibitors. J Pharmacol Exp Ther 279:247-54.nGomez WJ, Carvalho AC, Palma JH, Gon?alvez I Jr, Buffolo E. 1994. Vasoplegic syndrome: a new dilemma. J Thoracic Cardiovasc Surg 107:942-3.nGu YJ, Mariani MA, Boonstra PW, Grandjean JG, van Oeveren W. 1999. Complement activation in coronary artery bypass grafting patients without cardiopulmonary bypass: the role of tissue injury by surgical incision. Chest 116:892-8.nHaeffner-Cavaillon N, Roussellier N, Ponzio O, et al. 1989. Induction of interleukin-1 production in patients undergoing cardiopulmonary bypass. J Thorac Cardiovasc Surg 98:1100-6.nHatori N, Yoshizu H, Haga Y, et al. 1994. Biocompatibility of heparincoated membrane oxygenator during cardiopulmonary bypass. Artif Organs 18:904-910.nHendrik M, Sander JH, Hommes DW, et al. 1995. Treatment of Crohn's disease with anti-tumor necrosis factor chimeric monoclonal antibody (cA2). Gastroenterology 109:129-135.nKawamura T, Inada K, Okada H, Okada K, Wakusawa R. 1995. Methylprednisolone inhibits increase of interleukin 8 and 6 during open heart surgery. Can J Anaesth 42:399-403.nKawamura T, Wakusawa R, Okada K, Inada S. 1993. Elevation of cytokines during open heart surgery with cardiopulmonary bypass: participation of interleukin 8 and 6 in reperfusion injury. Can J Anaesth 40:1016-21.nJansen NJG, van Oeveren W, Gu YJ, van Vliet MH, Eijsman L, Wildevuur CRH. 1992. Endotoxin release and tumor necrosis factor formation during cardiopulmonary bypass. Ann Thorac Surg 54:744-8.nJournois D, Pouard P, Greeley WJ, Mauriat P, Vouhe P, Safran D. 1994. Hemofiltration during cardiopulmonary bypass in pediatric cardiac surgery. Effects on hemostasis cytokines, and complement components. Anesthesiology 81:1181-9.nMatsumori A, Ono K, Nishio R, Nose Y, Sasayama S. 1997. Amiodarone inhibits production of tumor necrosis factor-(by human mononuclear cells (a possible mechanism for its effect in heart failure). Circulation 96:1386-9.nMenasche P, Peynet J, Lariviere J, et al. 1994. Does normothermia during cardiopulmonary bypass increase neutrophil-endothelium interactions? Circulation 90:II 275-9.nMentzer RM Jr, Birjiniuk V, Khuri S, et al. 1999. Adenosine myocardial protection: preliminary results of a phase II clinical trial. Ann Surg 229:643-9.nMiller BE, Levy JH. 1997. The inflammatory response to cardiopulmonary bypass. J Cardiothorac Vasc Anesth 3:355-66.nMikko H, Matti T. 2001. Cytokine Responses and Anti-Inflammatory Strategies in Coronary Artery Bypass Grafting [academic dissertation]. Finland: Department of Surgery, Tampere University Hospital Medical School.nOz MC, Liao H, Naka Y, et al. 1995. Ischemia-induced interleukin-8 release after human heart transplantation. A potential role for endothelial cells. Circulation 92(suppl 9):II 428-32.nRosano GE, Sarrel PM, Poole-Wilson PA, Collins P. 1993. Beneficial effect of estrogen on exercise-induced myocardial ischaemia in women with coronary artery disease. Lancet 342:133-6.nRoyston D. 1996. Preventing the inflammatory response to open heart surgery: the role of aprotinin and other protease inhibitors. Int J Cardiol 53(suppl):S11-37.nMassoudy P, Becker BF, Gerlach E. 1995. Nitric oxide accounts for postischemic cardioprotection resulting from angiotensin-converting enzyme inhibition: indirect evidence for a radical scavenger effect in isolated guinea pig heart. J Cardiovasc Pharmacol 25:440-7.nMassoudy P, Zahler, S, Freyholdt T, et al. 2000. Sodium nitroprusside in patients with compromised left ventricular function undergoing coronary bypass: reduction of cardiac proinflammatory substances. J Thorac Surg 119:566-74.nHennein HA, Ebba H, Rodriguez JL, et al. 1994. Relationship of the proinflammatory cytokines to myocardial ischemia and dysfunction after uncomplicated coronary artery revascularization. J Thorac Cardiovasc Surg 108:626-35.nHill GE, Taylor JA, Robbins RA. 1997. Differing effects of aprotinin and (-aminocaproic acid on cytokine-induced inducible nitric oxide synthase expression. Ann Thorac Surg 63:74-7.nKim KU, Kwon OJ, Jue DM. 1993. Pro-tumour necrosis factor cleavage enzyme in macrophage membrane/particulate. Immunology 80:134-9.nLee HT, LaFaro RJ, Reed GE. 1995. Pretreatment of human myocardium with adenosine during open heart surgery. J Card Surg 10:665-76.nLiebold A, Langhammer TH, Brunger F, Birnbaum DE. 1999. Cardiac interleukin-6 release and myocardial recovery after aortic cross clamping. Crystalloid versus blood cardioplegia. J Cardiovasc Surg (Torino) 40:633-6.nWan S, Izzat MB, Lee TW, Wan IY, Tang NL, Yim AP. 1999. Avoiding cardiopulmonary bypass in multivessel CABG reduces cytokine response and myocardial injury. Ann Thorac Surg 68:52-7.nSteinberg JB, Kapelanski DP, Olson JD, Weiler JM. 1993. Cytokine and complement levels in patients undergoing cardiopulmonary bypass. J Thorac Cardiovasc Surg 106:1008-16.nTe Velthius H, Jansen PG, Hack CE, Eijsman L, Wildevuur CR. 1996. Specific complement inhibition with heparin-coated extracorporeal circuits. Ann Thorac Surg 61:1153-7.nTeoh KH, Bradley CA, Gauldie J, Burrows H. 1995. Steroid inhibition of cytokine-mediated vasodilation after warm heart surgery. Circulation 92(suppl 9):II347-53.nWan S, LeClerc JL, Vincent JL. 1997. Cytokine responses to cardiopulmonary bypass: lessons learned from cardiac transplantation. Ann Thorac Surg 63:269-76.nWan S, LeClerc JL, Vincent JL. 1997. Inflammatory response to cardiopulmonary bypass. Chest 112:676-92.nWan S, Marchant A, Desmet JM, et al. 1996. Human cytokine responses to cardiac transplantation and coronary artery bypass grafting. J Thorac Cardiovasc Surg 111:469-77.n



How to Cite

Abacilar, F., Dogan, O. F., Duman, U., Ucar, I., Demircin, M., Ersoy, U., Dogan, R., & Boke, E. (2006). The Changes and Effects of the Plasma Levels of Tumor Necrosis Factor after Coronary Artery Bypass Surgery with Cardiopulmonary Bypass. The Heart Surgery Forum, 9(4), E703-E709.




Most read articles by the same author(s)

1 2 3 > >>