The role of circulating inflammatory cytokines in cardiopulmonary bypass-related organs injuries and the treatments_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

ZHANG Jinghan ¹ , DU Lei ² ,  GOU Daming ³

1. Department of Anesthesiology, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, Guizhou, P. R. China;
2. Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, 610041, P. R. China;
3. Department of Anesthesiology, Kweichow Moutai Hospital, Zunyi, 564512, Guizhou, P. R. China;

Corresponding author：

GOU Daming, Email: gdmzy@yeah.net

Keywords：

Cardiopulmonary bypass; inflammatory reaction; circulating inflammatory factors; organs injuries; review

DOI：

10.7507/1007-4848.202302087

Video：

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Abstract Full text Figures/Tables Video References Cited by

Systemic inflammatory response (SIR) evoked by cardiopulmonary bypass (CPB) is still one of the major causes of postoperative multiple organs injuries. Since the concentrations of circulating inflammatory factors are positively associated with postoperative adverse events, removal or inhibition of inflammatory factors are considered as effective treatments to improve outcomes. After more than 20 years of research, however, the results are disappointed as neither neutralization nor removal of circulating inflammatory factors could reduce adverse events. Therefore, the role of circulating inflammatory factors in CPB-related organs injuries should be reconsidered in order to find effective therapies. Here we reviewed the association between circulating inflammatory factors and the outcomes, as well as the current therapies, including antibody and hemadsorption. Most importantly, the role of circulating inflammatory factors in SIR was reviewed, which may be helpful to develop new measures to prevent and treat CPB-related organs injuries.

Citation： ZHANG Jinghan, DU Lei, GOU Daming. The role of circulating inflammatory cytokines in cardiopulmonary bypass-related organs injuries and the treatments. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2025, 32(1): 129-135. doi: 10.7507/1007-4848.202302087 Copy

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2.	Hatami S, Hefler J, Freed DH. Inflammation and oxidative stress in the context of extracorporeal cardiac and pulmonary support. Front Immunol, 2022, 13: 831930.
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1. Gotts JE, Matthay MA, 王春耀. 全身性感染: 病理生理及临床管理. 英国医学杂志(中文版), 2017, 20(3): 143-162.Gotts JE, Matthay MA, Wang CY. Sepsis: Pathophysiology and clinical management. BMJ (Chin Ed), 2017, 20(3): 143-162.
2. Hatami S, Hefler J, Freed DH. Inflammation and oxidative stress in the context of extracorporeal cardiac and pulmonary support. Front Immunol, 2022, 13: 831930.
3. Squiccimarro E, Labriola C, Malvindi PG, et al. Prevalence and clinical impact of systemic inflammatory reaction after cardiac surgery. J Cardiothorac Vasc Anesth, 2019, 33(6): 1682-1690.
4. Khreba NA, Abdelsalam M, Wahab AM, et al. Kidney injury molecule 1 (KIM-1) as an early predictor for acute kidney injury in post-cardiopulmonary bypass (CPB) in open heart surgery patients. Int J Nephrol, 2019, 2019: 6265307.
5. Mazzeffi M, Zivot J, Buchman T, et al. In-hospital mortality after cardiac surgery: Patient characteristics, timing, and association with postoperative length of intensive care unit and hospital stay. Ann Thorac Surg, 2014, 97(4): 1220-1225.
6. Ltaief Z, Ben-Hamouda N, Rancati V, et al. Vasoplegic syndrome after cardiopulmonary bypass in cardiovascular surgery: Pathophysiology and management in critical care. J Clin Med, 2022, 11(21): 6407.
7. Devereaux PJ, Lamy A, Chan MTV, et al. High-sensitivity troponin I after cardiac surgery and 30-day mortality. N Engl J Med, 2022, 386(9): 827-836.
8. Lindman BR, Goldstein JS, Nassif ME, et al. Systemic inflammatory response syndrome after transcatheter or surgical aortic valve replacement. Heart, 2015, 101(7): 537-545.
9. Presta P, Bolignano D, Coppolino G, et al. Antecedent ACE-inhibition, inflammatory response, and cardiac surgery associated acute kidney injury. Rev Cardiovasc Med, 2021, 22(1): 207-213.
10. Puchinger J, Ryz S, Nixdorf L, et al. Characteristics of interleukin-6 signaling in elective cardiac surgery: A prospective cohort study. J Clin Med, 2022, 11(3): 590.
11. Franke A, Lante W, Fackeldey V, et al. Pro-inflammatory cytokines after different kinds of cardio-thoracic surgical procedures: Is what we see what we know? Eur J Cardiothorac Surg, 2005, 28(4): 569-575.
12. Poon KS, Palanisamy K, Chang SS, et al. Plasma exosomal miR-223 expression regulates inflammatory responses during cardiac surgery with cardiopulmonary bypass. Sci Rep, 2017, 7(1): 10807.
13. Song ST, Bai CM, Zhou JW. Serum TNF-α levels in children with congenital heart disease undergoing cardiopulmonary bypass: A cohort study in China and a meta-analysis of the published literature. J Clin Lab Anal, 2017, 31(6): e22112.
14. 张凡, 刘玉侠, 陈建文, 等. 人工心脏瓣膜置换术围术期心肌损伤生化标志物水平的变化及其意义. 蚌埠医学院学报, 2009, 34(8): 729-731.Zhang F, Liu YX, Chen JW, et al. Changes and significance of biochemical markers of myocardial damage in the perioperation of heart valve prosthesis replacement. J Bengbu Med Coll, 2009, 34(8): 729-731.
15. Arkader R, Troster EJ, Abellan DM, et al. Procalcitonin and C-reactive protein kinetics in postoperative pediatric cardiac surgical patients. J Cardiothorac Vasc Anesth, 2004, 18(2): 160-165.
16. Amouzeshi A, Abedi F, Zardast M, et al. Prognostic value of procalcitonin for morbidity and mortality in patients after cardiac surgery. Cardiol Res Pract, 2021, 2021: 1542551.
17. Bauer A, Korten I, Juchem G, et al. EuroScore and IL-6 predict the course in ICU after cardiac surgery. Eur J Med Res, 2021, 26(1): 29.
18. Everett AD, Alam SS, Owens SL, et al. The association between cytokines and 365-day readmission or mortality in adult cardiac surgery. J Extra Corpor Technol, 2019, 51(4): 201-209.
19. Chen Y, Lu S, Wu Y, et al. Change in serum level of interleukin 6 and delirium after coronary artery bypass graft. Am J Crit Care, 2019, 28(6): 462-470.
20. Liangos O, Kolyada A, Tighiouart H, et al. Interleukin-8 and acute kidney injury following cardiopulmonary bypass: A prospective cohort study. Nephron Clin Pract, 2009, 113(3): c148-c154.
21. Zhou Y, Liu L, Gao C, et al. Puerarin pre-conditioning on the expression levels of CK-MB, cTnI and inflammatory factors in patients undergoing cardiac valve replacement. Exp Ther Med, 2019, 17(4): 2598-2602.
22. Ben-Abraham R, Weinbroum AA, Lotan D, et al. Interleukin-8 secretion following cardiopulmonary bypass in children as a marker of early postoperative morbidity. Paediatr Anaesth, 2002, 12(2): 156-161.
23. Holmes JH, Connolly NC, Paull DL, et al. Magnitude of the inflammatory response to cardiopulmonary bypass and its relation to adverse clinical outcomes. Inflamm Res, 2002, 51(12): 579-586.
24. Tomasdottir H, Hjartarson H, Ricksten A, et al. Tumor necrosis factor gene polymorphism is associated with enhanced systemic inflammatory response and increased cardiopulmonary morbidity after cardiac surgery. Anesth Analg, 2003, 97(4): 944-949.
25. Bittar MN, Carey JA, Barnard JB, et al. Tumor necrosis factor alpha influences the inflammatory response after coronary surgery. Ann Thorac Surg, 2006, 81(1): 132-137.
26. Abacilar F, Dogan OF, Duman U, et al. The changes and effects of the plasma levels of tumor necrosis factor after coronary artery bypass surgery with cardiopulmonary bypass. Heart Surg Forum, 2006, 9(4): E703-E709.
27. Susantitaphong P, Perianayagam MC, Tighiouart H, et al. Tumor necrosis factor alpha promoter polymorphism and severity of acute kidney injury. Nephron Clin Pract, 2013, 123(1-2): 67-73.
28. 孙炎华, 林如明, 赖兆新, 等. 胆红素和C反应蛋白预测急性心肌梗死患者支架术后长期预后的意义. 岭南心血管病杂志, 2019, 25(6): 610-612, 621.Sun YH, Lin RM, Lai ZX, et al. Significance of bilirubin and C-reactive protein in predicting long-term prognosis of patients with acute myocardial infarction after coronary stent implantation. South China J Cardiovasc Dis, 2019, 25(6): 610-612, 621.
29. Allan CK, Newburger JW, McGrath E, et al. The relationship between inflammatory activation and clinical outcome after infant cardiopulmonary bypass. Anesth Analg, 2010, 111(5): 1244-1251.
30. Fritz HG, Brandes H, Bredle DL, et al. Post-operative hypoalbuminaemia and procalcitonin elevation for prediction of outcome in cardiopulmonary bypass surgery. Acta Anaesthesiol Scand, 2003, 47(10): 1276-1283.
31. Celebi S, Koner O, Menda F, et al. Procalcitonin kinetics in pediatric patients with systemic inflammatory response after open heart surgery. Intensive Care Med, 2006, 32(6): 881-887.
32. Sablotzki A, Dehne M G, Friedrich I, et al. Different expression of cytokines in survivors and non-survivors from MODS following cardiovascular surgery. Eur J Med Res, 2003, 8(2): 71-76.
33. Hou L, Yang Z, Wang Z, et al. NLRP3/ASC-mediated alveolar macrophage pyroptosis enhances HMGB1 secretion in acute lung injury induced by cardiopulmonary bypass. Lab Invest, 2018, 98(8): 1052-1064.
34. Kim N, Lee S, Lee JR, et al. Prognostic role of serum high mobility group box 1 concentration in cardiac surgery. Sci Rep, 2020, 10(1): 6293.
35. Greenberg JH, Whitlock R, Zhang WR, et al. Interleukin-6 and interleukin-10 as acute kidney injury biomarkers in pediatric cardiac surgery. Pediatr Nephrol, 2015, 30(9): 1519-1527.
36. Yang Z, Zingarelli B, Szabó C. Crucial role of endogenous interleukin-10 production in myocardial ischemia/reperfusion injury. Circulation, 2000, 101(9): 1019-1026.
37. Goulet DR, Atkins WM. Considerations for the design of antibody-based therapeutics. J Pharm Sci, 2020, 109(1): 74-103.
38. Castelli MS, McGonigle P, Hornby PJ. The pharmacology and therapeutic applications of monoclonal antibodies. Pharmacol Res Perspect, 2019, 7(6): e00535.
39. Tanaka T, Narazaki M, Kishimoto T. Interleukin (IL-6) immunotherapy. Cold Spring Harb Perspect Biol, 2018, 10(8).
40. Xu X, Han M, Li T, et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci U S A, 2020, 117(20): 10970-10975.
41. Cheng C, Xu JM, Yu T. Neutralizing IL-6 reduces heart injury by decreasing nerve growth factor precursor in the heart and hypothalamus during rat cardiopulmonary bypass. Life Sci, 2017, 178: 61-69.
42. Yang S, Hu S, Choudhry MA, et al. Anti-rat soluble IL-6 receptor antibody down-regulates cardiac IL-6 and improves cardiac function following trauma-hemorrhage. J Mol Cell Cardiol, 2007, 42(3): 620-630.
43. Ma M, Sun Q, Li X, et al. Blockade of IL-6/IL-6R signaling attenuates acute antibody-mediated rejection in a mouse cardiac transplantation model. Front Immunol, 2021, 12: 778359.
44. Miller CL, Madsen JC. Targeting IL-6 to prevent cardiac allograft rejection. Am J Transplant, 2022, 22 (Suppl 4): 12-17.
45. Bao Z, Ye Q, Gong W, et al. Humanized monoclonal antibody against the chemokine CXCL-8 (IL-8) effectively prevents acute lung injury. Int Immunopharmacol, 2010, 10(2): 259-263.
46. Yu Y, Gao M, Li H, et al. Pulmonary artery perfusion with anti-tumor necrosis factor alpha antibody reduces cardiopulmonary bypass-induced inflammatory lung injury in a rabbit model. PLoS One, 2013, 8(12): e83236.
47. Qi D, Gao MX, Yu Y. Intratracheal antitumor necrosis factor-α antibody attenuates lung tissue damage following cardiopulmonary bypass. Artif Organs, 2013, 37(2): 142-149.
48. Deng Y, Hou L, Xu Q, et al. Cardiopulmonary bypass induces acute lung injury via the high-mobility group box 1/toll-like receptor 4 pathway. Dis Markers, 2020, 2020: 8854700.
49. Liu MH, Yu H, Zhou RH. Application of adsorptive blood purification techniques during cardiopulmonary bypass in cardiac surgery. Oxid Med Cell Longev, 2022, 2022: 6584631.
50. Bonavia A, Groff A, Karamchandani K, et al. Clinical utility of extracorporeal cytokine hemoadsorption therapy: A literature review. Blood Purif, 2018, 46(4): 337-349.
51. Garau I, März A, Sehner S, et al. Hemadsorption during cardiopulmonary bypass reduces interleukin 8 and tumor necrosis factor α serum levels in cardiac surgery: A randomized controlled trial. Minerva Anestesiol, 2019, 85(7): 715-723.
52. Hohn A, Baumann A, Pietroschinsky E, et al. Hemoadsorption: Effective in reducing circulating fragments of the endothelial glycocalyx during cardiopulmonary bypass in patients undergoing on-pump cardiac surgery? Minerva Anestesiol, 2021, 87(1): 35-42.
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