Postoperative interleukin-8 levels are related to the duration of coronary artery bypass grafting surgery and predict in-hospital postsurgical complications

Zsombor Mathe 1 , Razvan Constantin Serban 1 , Irina Pintilie 2 , Cristina Somkereki 1 , Adina Hutanu 3 ,  and Alina Scridon 3
  • 1 University of Medicine and Pharmacy of Tîrgu Mureș, , Emergency Institute for Cardiovascular Diseases and Transplantation Tîrgu Mureș, , Romania
  • 2 Emergency Institute for Cardiovascular Diseases and Transplantation Tîrgu Mureș, , Center for Advanced Medical and Pharmaceutical Research Tîrgu Mureș, , Romania
  • 3 University of Medicine and Pharmacy of Tîrgu Mureș, , Center for Advanced Medical and Pharmaceutical Research Tîrgu Mureș, , Romania


Introduction: The magnitude of the very early coronary artery bypass grafting (CABG)-related inflammatory response has been shown to influence post-CABG outcomes. However, the dynamics of the systemic inflammatory response to CABG beyond the very early postoperative phase and its relevance to clinical outcomes are not fully understood.

Methods: Circulating levels of several inflammatory markers were determined in 30 consecutive patients undergoing elective isolated on-pump CABG one day prior (D0-1), and 2 (D2) and 5 days post-CABG.

Results: CABG was associated with a significant increase in all studied inflammatory marker levels (all p<0.05 for D2 versus D0-1). D2 post-CABG IL-6 and IL-8 levels were both significantly positively correlated with extracorporeal circulation (ECC) and aortic clamping (AC) times (all p<0.05), whereas a weaker correlation was observed between D2 post-CABG IL-8 levels and total surgery time (r=0.42, p=0.02). In multiple regression analysis, D2 IL-8 levels independently predicted post-CABG kidney (p= 0.02) and liver (p = 0.04) dysfunction, as well as a sum of post-CABG major complications ≥2 (p = 0.04).

Conclusions: In this prospective study, longer duration of cardiopulmonary bypass caused a larger post-CABG inflammatory surge, whereas the duration of total CABG surgery had a less significant effect. IL-8 hyperresponders had greater risk of developing kidney and liver dysfunction and presented more major post-CABG complications. These data suggest that targeting the IL-8 pathway using antiinflammatory agents, or simply by shortening the duration of cardiopulmonary bypass could improve the in-hospital post-CABG outcomes in this population.

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  • 1. Moazzami K, Dolmatova E, Maher J, Gerula C, Sambol J, Klapholz M, et al. In-hospital outcomes and complications of coronary artery bypass grafting in the United States between 2008 and 2012. J Cardiothorac Vasc Anesth. 2017;31(1):19-25. DOI: 10.1053/j.jvca.2016.08.008

  • 2. Yamaji K, Ueki Y, Souteyrand G, Daemen J, Wiebe J, Nef H, et al. Mechanisms of very late bioresorbable scaffold thrombosis: The INVEST registry. J Am Coll Cardiol. 2017;70(19):2330-44. DOI: 10.1016/j.jacc.2017.09.014

  • 3. Șerban R, Scridon A, Dobreanu D, Elkaholut A. Coronary artery aneurysm formation within everolimus-eluting bioresorbable stent. Int J Cardiol. 2014;177:e4-5. DOI: 10.1016/j.ijcard.2014.07.197

  • 4. DiNicolantonio JJ, D’Ascenzo F, Tomek A, Chatterjee S, Niazi AK, Biondi-Zoccai G. Clopidogrel is safer than ticagrelor in regard to bleeds: a closer look at the PLATO trial. Int J Cardiol. 2013;168(3):1739-44. DOI: 10.1016/j.ijcard.2013.06.135

  • 5. Mohr FW, Morice MC, Kappetein AP, Feldman TE, Ståhle E, Colombo A, et al. Coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with three-vessel disease and left main coronary disease: 5-year follow-up of the randomised, clinical SYNTAX trial. Lancet. 2013;381:629-38. DOI: 10.1016/S0140-6736(13)60141-5

  • 6. Piątek J, Kędziora A, Konstanty-Kalandyk J, Kiełbasa G, Olszewska M, Song BH, et al. Risk factors for in-hospital mortality after coronary artery bypass grafting in patients 80 years old or older: a retrospective case-series study. PeerJ. 2016;4:e2667. DOI: 10.7717/peerj.2667

  • 7. Turrentine FE, Wang H, Simpson VB, Jones RS. Surgical risk factors, morbidity, and mortality in elderly patients. J Am Coll Surg. 2006;203(6):865-77. DOI: 10.1016/j.jamcollsurg.2006.08.026

  • 8. Poole L, Kidd T, Leigh E, Ronaldson A, Jahangiri M, Steptoea A. Depression, C-reactive protein and length of post-operative hospital stay in coronary artery bypass graft surgery patients. Brain Behav Immun. 2014;37(100):115-21. DOI: 10.1016/j.bbi.2013.11.008

  • 9. Holmes JH 4th, Connolly NC, Paull DL, Hill ME, Guyton SW, Ziegler SF, et al. Magnitude of the inflammatory response to cardiopulmonary bypass and its relation to adverse clinical outcomes. Inflamm Res. 2002;51(12):579-86. DOI: 10.1007/PL00012432

  • 10. Royston D. Serine protease inhibition prevents both cellular and humoral responses to cardiopulmonary bypass. J Cardiovasc Pharmacol. 1996;27(Suppl. 1):S42-9. DOI: 10.1097/00005344-199600001-00010

  • 11. Cernea S, Şular FL, Huţanu A, Voidăzan S. Markers of cognitive impairment in patients with type 2 diabetes. Rev Rom Med Lab. 2016;24(2):161-76. DOI: 10.1515/rrlm-2016-0023

  • 12. Hennein HA, Ebba H, Rodriguez JL, Merrick SH, Keith FM, Bronstein MH, et al. Relationship of the proinflammatory cytokines to myocardial ischemia and dysfunction after uncomplicated coronary revascularization. J Thorac Cardiovasc Surg. 1994;108(4):626-35.

  • 13. Bruins P, te Velthuis H, Yazdanbakhsh AP, Jansen PG, van Hardevelt FW, de Beaumont EM, et al. Activation of the complement system during and after cardiopulmonary bypass surgery: postsurgery activation involves C-reactive protein and is associated with postoperative arrhythmia. Circulation. 1997;96(10):3542-8. DOI: 10.1161/01.CIR.96.10.3542

  • 14. Finkel MS, Oddis CV, Jacob TD, Watkins SC, Hattier BG, Simmons RL. Negative inotropic effects of cytokines on the heart mediated by nitric oxide. Science. 1992;257:387-9. DOI: 10.1126/science.1631560

  • 15. Van Zee KJ, Fischer E, Hawes AS, Hébert CA, Terrell TG, Baker JB, et al. Effects of intravenous IL-8 administration in nonhuman primates. J Immunol. 1992;148(6):1746-52.

  • 16. Mitchell JD, Grocott HP, Phillips-Bute B, Mathew JP, Newman MF, Bar-Yosef S. Cytokine secretion after cardiac surgery and its relationship to postoperative fever. Cytokine. 2007;38(1):37-42. DOI: 10.1016/j.cyto.2007.04.009

  • 17. Metinko A, Kunkel S, Standiford T, Streter R. Monocyte expression of interleukin-8 in response to oxidant stress. FASEB J Abstracts Part 1. 1991:1941;A704 (Abstract).

  • 18. Søraas CL, Friis C, Engebretsen KV, Sandvik L, Kjeldsen SE, Tønnessen T. Troponin T is a better predictor than creatine kinase-MB of long-term mortality after coronary artery bypass graft surgery. Am Heart J. 2012;164(5):779-85. DOI: 10.1016/j.ahj.2012.05.027

  • 19. Kawamura T, Wakusawa R, Okada K, Inada S. Elevation of cytokines during open heart surgery with cardio-pulmonary bypass: participation of interleukin 8 and 6 in reperfusion injury. Can J Anaesth. 1993;40(11):1016-21. DOI: 10.1007/BF03009470

  • 20. Wu ZK, Laurikka J, Vikman S, Nieminen R, Moilanen E, Tarkka MR. High postoperative interleukin-8 levels related to atrial fibrillation in patients undergoing coronary artery bypass surgery. World J Surg. 2008;32(12):2643-9. DOI: 10.1007/s00268-008-9758-7

  • 21. Kirklin, JW, Barratt-Boyes, BG. Hypothermia, circulatory arrest, and cardiopulmonary bypass. In: Cardiac surgery. 2nd ed. Churchill Livingstone, New York; 1993: 61-128.

  • 22. Gurbuz O, Kumtepe G, Ercan A, Yolgosteren A, Ozkan H, Karal IH, et al. A comparison of off- and on-pump beating-heart coronary artery bypass surgery on long-term cardiovascular events. Cardiovasc J Afr. 2017;28(1):30-5. DOI: 10.5830/CVJA-2016-049

  • 23. Wang J, Yu W, Zhao D, Liu N, Yu Y. In-hospital and long-term mortality in 35,173 Chinese patients undergoing coronary artery bypass grafting in Beijing: impact of sex, age, myocardial infarction, and cardiopulmonary bypass. J Cardiothorac Vasc Anesth. 2017;31(1):26-31. DOI: 10.1053/j.jvca.2016.08.004

  • 24. Takagi H, Umemoto T. All-Literature Investigation of Cardiovascular Evidence (ALICE) Group: Worse long-term survival after off-pump than on-pump coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2014;148:1820-9. DOI: 10.1016/j.jtcvs.2014.05.034

  • 25. Mathison M, Edgerton JR, Horswell JL, Akin JJ, Mack MJ. Analysis of hemodynamic changes during beating heart surgical procedures. Ann Thorac Surg. 2000;70:1355-60. DOI: 10.1016/S0003-4975(00)01590-3

  • 26. Göber V, Hohl A, Gahl B, Dick F, Eigenmann V, Carrel TP, et al. Early troponin T and prediction of potentially correctable in-hospital complications after coronary artery bypass grafting surgery. PLoS One. 2013;8(9):e74241. DOI: 10.1371/journal.pone.0074241

  • 27. Lehrke S, Steen H, Sievers HH, Peters H, Opitz A, Müller-Bardorff M, et al. Cardiac troponin T for prediction of short- and long-term morbidity and mortality after elective open heart surgery. Clin Chem. 2004;50(9):1560-7. DOI: 10.1373/clinchem.2004.031468

  • 28. Kathiresan S, Servoss SJ, Newell JB, Trani D, Mac-Gillivray TE, Lewandrowski K, et al. Cardiac troponin T elevation after coronary artery bypass grafting is associated with increased one-year mortality. Am J Cardiol. 2004;94(7):879-81. DOI: 10.1016/j.amj-card.2004.06.022

  • 29. Carrier M, Pellerin M, Perrault LP, Solymoss BC, Pelletier LC. Troponin levels in patients with myocardial infarction after coronary artery bypass grafting. Ann Thorac Surg. 2000;69(2):435-40. DOI: 10.1016/S0003-4975(99)01294-1

  • 30. Mukaida N, Shiroo M, Matsusima K. Genomic structure of the human monocyte-derived neutrophil chemo-tactic factor IL-8. J Immunol. 1989;143:1366-71.

  • 31. Standiford TJ, Strieter RM, Chensue SI, Westwick J, Kasahara K, Kunkel SL. IL-4 inhibits the expression of IL-8 from stimulated monocytes. J Immunol. 1990;145:1435-9.


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