Tranexamic acid inhibits pulmonary inflammatory response induced by cardiopulmonary bypass_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

YU Songliang , LIU Chaonan , LING Liqin , CHEN Si , LI Qin , MI Jian ,  ZHOU Jing

Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, P.R.China;

Corresponding author：

ZHOU Jing, Email: zhoujinghuaxi@163.com

Keywords：

Cardiopulmonary bypass; tranexamic acid; acute lung injury

DOI：

10.7507/1007-4848.201912089

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the effect of different administration methods of tranexamic acid on postoperative pulmonary inflammation response during cardiopulmonary bypass (CPB).Methods A total of 64 SD rats were included in the study. They were randomly divided into eight different groups. CPB model was established for the operation groups. The rats in the operation groups were given tranexamic acid at low (25 mg/kg), medium (50 mg/kg) or high (100 mg/kg) concentrations before or after the CPB. Blood cells count and coagulation function were assessed 1 hour after surgery. The concentration of interleukin (IL)-1β、IL-6 and tumor necrosis factor (TNF)-α in blood and lung lavage fluid were measured. The infiltration of inflammatory cells in lungs was observed by hematoxylin-eosin (HE) staining.Results The concentration of inflammatory cells in the operation groups was higher than that in the control group (P<0.05). The use of tranexamic acid inhibited the increase of IL-6 and TNF-α in whole blood and lung lavage fluid due to CPB (P<0.05), but there was no significant difference among the experimental groups (P>0.05). Tranexamic acid could reduce the exudation of inflammatory cells in the lungs.Conclusion The use of tranexamic acid can effectively reduce the release of inflammatory factors and reduce acute lung injury caused by CPB in rat models. But simply increasing the dose or changing the timing of administration is not more effective in reducing the intensity of the inflammatory response.

Citation： YU Songliang, LIU Chaonan, LING Liqin, CHEN Si, LI Qin, MI Jian, ZHOU Jing. Tranexamic acid inhibits pulmonary inflammatory response induced by cardiopulmonary bypass. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2020, 27(8): 933-939. doi: 10.7507/1007-4848.201912089 Copy

1.	Ng CS, Wan S, Yim AP, et al. Pulmonary dysfunction after cardiac surgery. Chest, 2002, 121(4): 1269-1277.
2.	Bignami E, Guarnieri M, Saglietti F, et al. Mechanical ventilation during cardiopulmonary bypass. J Cardiothorac Vasc Anesth, 2016, 30(6): 1668-1675.
3.	Sievers HH, Freund-Kaas C, Eleftheriadis S, et al. Lung protection during total cardiopulmonary bypass by isolated lung perfusion: preliminary results of a novel perfusion strategy. Ann Thorac Surg, 2002, 74(4): 1167-1172.
4.	Kiessling AH, Guo FW, Gökdemir Y, et al. The influence of selective pulmonary perfusion on the inflammatory response and clinical outcome of patients with chronic obstructive pulmonary disease undergoing cardiopulmonary bypass. Interact Cardiovasc Thorac Surg, 2014, 18(6): 732-739.
5.	Ranucci M, Ballotta A, La Rovere MT, et al. Postoperative hypoxia and length of intensive care unit stay after cardiac surgery: the underweight paradox? PLoS One, 2014, 9(4): e93992.
6.	Graham EM, Atz AM, Gillis J, et al. Differential effects of aprotinin and tranexamic acid on outcomes and cytokine profiles in neonates undergoing cardiac surgery. J Thorac Cardiovasc Surg, 2012, 143(5): 1069-1076.
7.	Rappold JF, Pusateri AE. Tranexamic acid in remote damage control resuscitation. Transfusion, 2013, 53(Suppl 1): 96S-99S.
8.	Sigaut S, Tremey B, Ouattara A, et al. Comparison of two doses of tranexamic acid in adults undergoing cardiac surgery with cardiopulmonary bypass. Anesthesiology, 2014, 120(3): 590-600.
9.	Esfandiari BR, Bistgani MM, Kabiri M. Low dose tranexamic acid effect on post-coronary artery bypass grafting bleeding. Asian Cardiovasc Thorac Ann, 2013, 21(6): 669-674.
10.	Mangano DT, Miao Y, Vuylsteke A, et al. Mortality associated with aprotinin during 5 years following coronary artery bypass graft surgery. JAMA, 2007, 297(5): 471-479.
11.	Carter DW, Prudovsky I, Kacer D, et al. Tranexamic acid suppresses the release of mitochondrial DAMPs and reduces lung inflammation in a murine burn model. J Trauma Acute Care Surg, 2019, 86(4): 617-624.
12.	Jimenez JJ, Iribarren JL, Lorente L, et al. Tranexamic acid attenuates inflammatory response in cardiopulmonary bypass surgery through blockade of fibrinolysis: a case control study followed by a randomized double-blind controlled trial. Crit Care, 2007, 11(6): R117.
13.	Chen TT, Liu JD, Wang G, et al. Combined treatment of ulinastatin and tranexamic acid provides beneficial effects by inhibiting inflammatory and fibrinolytic response in patients undergoing heart valve replacement surgery. Heart Surg Forum, 2013, 16(1): E38-E47.
14.	Peng Z, Ban K, LeBlanc A, et al. Intraluminal tranexamic acid inhibits intestinal sheddases and mitigates gut and lung injury and inflammation in a rodent model of hemorrhagic shock. J Trauma Acute Care Surg, 2016, 81(2): 358-365.
15.	Li Q, Laumonnier Y, Syrovets T, et al. Plasmin triggers cytokine induction in human monocyte-derived macrophages. Arterioscler Thromb Vasc Biol, 2007, 27(6): 1383-1389.
16.	Sugimoto MA, Ribeiro A, Costa BRC, et al. Plasmin and plasminogen induce macrophage reprogramming and regulate key steps of inflammation resolution via annexin A1. Blood, 2017, 129(21): 2896-2907.
17.	Syrovets T, Jendrach M, Rohwedder A, et al. Plasmin-induced expression of cytokines and tissue factor in human monocytes involves AP-1 and IKKbeta-mediated NF-kappa B activation. Blood, 2001, 97(12): 3941-3950.
18.	Du Y, Xu J, Wang G, et al. Comparison of two tranexamic acid dose regimens in patients undergoing cardiac valve surgery. J Cardiothorac Vasc Anesth, 2014, 28(5): 1233-1237.
19.	Faraoni D, Cacheux C, Van Aelbrouck C, et al. Effect of two doses of tranexamic acid on fibrinolysis evaluated by thromboelastography during cardiac surgery: a randomised, controlled study. Eur J Anaesthesiol, 2014, 31(9): 491-498.
20.	Andersson L, Nilsoon IM, Colleen S, et al. Role of urokinase and tissue activator in sustaining bleeding and the management thereof with EACA and AMCA. Ann N Y Acad Sci, 1968, 146(2): 642-658.

1. Ng CS, Wan S, Yim AP, et al. Pulmonary dysfunction after cardiac surgery. Chest, 2002, 121(4): 1269-1277.
2. Bignami E, Guarnieri M, Saglietti F, et al. Mechanical ventilation during cardiopulmonary bypass. J Cardiothorac Vasc Anesth, 2016, 30(6): 1668-1675.
3. Sievers HH, Freund-Kaas C, Eleftheriadis S, et al. Lung protection during total cardiopulmonary bypass by isolated lung perfusion: preliminary results of a novel perfusion strategy. Ann Thorac Surg, 2002, 74(4): 1167-1172.
4. Kiessling AH, Guo FW, Gökdemir Y, et al. The influence of selective pulmonary perfusion on the inflammatory response and clinical outcome of patients with chronic obstructive pulmonary disease undergoing cardiopulmonary bypass. Interact Cardiovasc Thorac Surg, 2014, 18(6): 732-739.
5. Ranucci M, Ballotta A, La Rovere MT, et al. Postoperative hypoxia and length of intensive care unit stay after cardiac surgery: the underweight paradox? PLoS One, 2014, 9(4): e93992.
6. Graham EM, Atz AM, Gillis J, et al. Differential effects of aprotinin and tranexamic acid on outcomes and cytokine profiles in neonates undergoing cardiac surgery. J Thorac Cardiovasc Surg, 2012, 143(5): 1069-1076.
7. Rappold JF, Pusateri AE. Tranexamic acid in remote damage control resuscitation. Transfusion, 2013, 53(Suppl 1): 96S-99S.
8. Sigaut S, Tremey B, Ouattara A, et al. Comparison of two doses of tranexamic acid in adults undergoing cardiac surgery with cardiopulmonary bypass. Anesthesiology, 2014, 120(3): 590-600.
9. Esfandiari BR, Bistgani MM, Kabiri M. Low dose tranexamic acid effect on post-coronary artery bypass grafting bleeding. Asian Cardiovasc Thorac Ann, 2013, 21(6): 669-674.
10. Mangano DT, Miao Y, Vuylsteke A, et al. Mortality associated with aprotinin during 5 years following coronary artery bypass graft surgery. JAMA, 2007, 297(5): 471-479.
11. Carter DW, Prudovsky I, Kacer D, et al. Tranexamic acid suppresses the release of mitochondrial DAMPs and reduces lung inflammation in a murine burn model. J Trauma Acute Care Surg, 2019, 86(4): 617-624.
12. Jimenez JJ, Iribarren JL, Lorente L, et al. Tranexamic acid attenuates inflammatory response in cardiopulmonary bypass surgery through blockade of fibrinolysis: a case control study followed by a randomized double-blind controlled trial. Crit Care, 2007, 11(6): R117.
13. Chen TT, Liu JD, Wang G, et al. Combined treatment of ulinastatin and tranexamic acid provides beneficial effects by inhibiting inflammatory and fibrinolytic response in patients undergoing heart valve replacement surgery. Heart Surg Forum, 2013, 16(1): E38-E47.
14. Peng Z, Ban K, LeBlanc A, et al. Intraluminal tranexamic acid inhibits intestinal sheddases and mitigates gut and lung injury and inflammation in a rodent model of hemorrhagic shock. J Trauma Acute Care Surg, 2016, 81(2): 358-365.
15. Li Q, Laumonnier Y, Syrovets T, et al. Plasmin triggers cytokine induction in human monocyte-derived macrophages. Arterioscler Thromb Vasc Biol, 2007, 27(6): 1383-1389.
16. Sugimoto MA, Ribeiro A, Costa BRC, et al. Plasmin and plasminogen induce macrophage reprogramming and regulate key steps of inflammation resolution via annexin A1. Blood, 2017, 129(21): 2896-2907.
17. Syrovets T, Jendrach M, Rohwedder A, et al. Plasmin-induced expression of cytokines and tissue factor in human monocytes involves AP-1 and IKKbeta-mediated NF-kappa B activation. Blood, 2001, 97(12): 3941-3950.
18. Du Y, Xu J, Wang G, et al. Comparison of two tranexamic acid dose regimens in patients undergoing cardiac valve surgery. J Cardiothorac Vasc Anesth, 2014, 28(5): 1233-1237.
19. Faraoni D, Cacheux C, Van Aelbrouck C, et al. Effect of two doses of tranexamic acid on fibrinolysis evaluated by thromboelastography during cardiac surgery: a randomised, controlled study. Eur J Anaesthesiol, 2014, 31(9): 491-498.
20. Andersson L, Nilsoon IM, Colleen S, et al. Role of urokinase and tissue activator in sustaining bleeding and the management thereof with EACA and AMCA. Ann N Y Acad Sci, 1968, 146(2): 642-658.

Previous Article
胃癌腹腔灌注化疗的并发症及预防
Next Article
An improved method for calculating liver volume in partial hepatectomy in rats

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Tranexamic acid inhibits pulmonary inflammatory response induced by cardiopulmonary bypass

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content