Research advances on extracorporeal membrane oxygenation in rat model_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

WANG Tianlong , YAN Weidong ,  JI Bingyang

Department of Cardiopulmonary Bypass, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, P. R. China;

Corresponding author：

JI Bingyang, Email: jibingyang@fuwai.com

Keywords：

Extracorporeal membrane oxygenation; animal experiment; rats; review

DOI：

10.7507/1007-4848.202305012

Video：

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Extracorporeal membrane oxygenation (ECMO) is a critical life support technique for patients with severe cardiopulmonary failure. Establishing a stable ECMO animal model is essential to further investigate the effects of ECMO on the body and provide assistance for optimizing ECMO management strategies and preventing complications in clinical practice. In recent years, rats have been widely used to establish ECMO models due to their low cost and good reproducibility. Therefore, this article provided a comprehensive review of literature on the ECMO rat model, including equipment and experimental management strategies. It offers a theoretical foundation for the development of a stable and mature ECMO rat model in the future.

Citation： WANG Tianlong, YAN Weidong, JI Bingyang. Research advances on extracorporeal membrane oxygenation in rat model. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2024, 31(6): 915-921. doi: 10.7507/1007-4848.202305012 Copy

1.	Li ZJ, Zhang DF, Zhang WH. Analysis of nosocomial infection and risk factors in patients with ECMO treatment. Infect Drug Resist, 2021, 14: 2403-2410.
2.	Mahmoud AA, Avedissian SN, Al-Qamari A, et al. Pharmacokinetic assessment of pre- and post-oxygenator vancomycin concentrations in extracorporeal membrane oxygenation: A prospective observational study. Clin Pharmacokinet, 2020, 59(12): 1575-1587.
3.	Pequignot B, Lescroart M, Orlowski S, et al. Methylene blue reduces fluid loading and norepinephrine requirements for post-resuscitation syndrome in a pig model of refractory cardiac arrest resuscitated with veno-arterial ECMO. J Clin Med, 2022, 11(9): 2515.
4.	Qi J, Gao S, Liu G, et al. An ovine model of awake veno-arterial extracorporeal membrane oxygenation. Front Vet Sci, 2021, 8: 809487.
5.	Tweddell JS, Kharnaf M, Zafar F, et al. Targeting the contact system in a rabbit model of extracorporeal membrane oxygenation. Blood Adv, 2023, 7(8): 1404-1417.
6.	薛平菲, 于洁, 黑飞龙. 大鼠静脉-动脉体外膜氧合模型研究进展. 中国体外循环杂志, 2019, 17(5): 318-320.
7.	陈原森, 刘子泉, 王海旺, 等. 大鼠体外膜肺氧合设备的研制与模型应用. 中华灾害救援医学, 2021, 9(8): 1171-1175.
8.	Juhl L, Petersen KA, Larsen EH, et al. The in vivo effect of adrenomedullin on rat dural and pial arteries. Eur J Pharmacol, 2006, 538(1-3): 101-107.
9.	Janata A, Drabek T, Magnet IA, et al. Extracorporeal versus conventional cardiopulmonary resuscitation after ventricular fibrillation cardiac arrest in rats: A feasibility trial. Crit Care Med, 2013, 41(9): e211-e222.
10.	Chang RW, Luo CM, Yu HY, et al. Investigation of the pathophysiology of cardiopulmonary bypass using rodent extracorporeal life support model. BMC Cardiovasc Disord, 2017, 17(1): 123.
11.	Ahmed N, Laghari AH, AlBkhoor B, et al. Fingolimod plays role in attenuation of myocardial injury related to experimental model of cardiac arrest and extracorporeal life support resuscitation. Int J Mol Sci, 2019, 20(24): 6237.
12.	于洁, 薛平菲, 陈书弘, 等. 大鼠体外心肺复苏模型的建立与评价. 中国体外循环杂志, 2020, 18(1): 44-47.
13.	薛平菲, 于洁, 秦春妮, 等. 无血预充大鼠体外心肺复苏模型的建立及支持效果评价. 中国分子心脏病学杂志, 2021, 21(1): 3748-3752.
14.	陈燕桦, 张炳东, 梁东科, 等. 体外膜肺氧合对急性肺损伤治疗的实验研究. 中国现代医学杂志, 2011, 21(19): 2215-2218.
15.	Ali AA, Downey P, Singh G, et al. Rat model of veno-arterial extracorporeal membrane oxygenation. J Transl Med, 2014, 12: 37.
16.	Fujii Y, Tatsumi E, Nakamura F, et al. PaO₂ greater than 300 mm Hg promotes an inflammatory response during extracorporeal circulation in a rat extracorporeal membrane oxygenation model. J Thorac Dis, 2020, 12(3): 749-757.
17.	Edinger F, Schneck E, Schulte C, et al. Comparison of the effect of membrane sizes and fibre arrangements of two membrane oxygenators on the inflammatory response, oxygenation and decarboxylation in a rat model of extracorporeal membrane oxygenation. BMC Cardiovasc Disord, 2020, 20(1): 294.
18.	Edinger F, Schmitt C, Koch C, et al. Application of alpha1-antitrypsin in a rat model of veno-arterial extracorporeal membrane oxygenation. Sci Rep, 2021, 11(1): 15849.
19.	Fujii Y, Abe T, Ikegami K. Diabetic pathophysiology enhances inflammation during extracorporeal membrane oxygenation in a rat model. Membranes (Basel), 2021, 11(4): 283.
20.	Umei N, Lai A, Miller J, et al. Establishment and evaluation of a rat model of extracorporeal membrane oxygenation (ECMO) thrombosis using a 3D-printed mock-oxygenator. J Transl Med, 2021, 19(1): 179.
21.	Xing Y, Cheng D, Shi C, et al. The protective role of YTHDF1-knock down macrophages on the immune paralysis of severe sepsis rats with ECMO. Microvasc Res, 2021, 137: 104178.
22.	Cheng X, Zhang R, Wei S, et al. Dexamethasone alleviates myocardial injury in a rat model of acute myocardial infarction supported by venoarterial extracorporeal membrane oxygenation. Front Public Health, 2022, 10: 900751.
23.	Edinger F, Schneck E, Schulte C, et al. Impact of the inspiratory oxygen fraction on the cardiac output during jugulo-femoral venoarterial extracorporeal membrane oxygenation in the rat. BMC Cardiovasc Disord, 2022, 22(1): 174.
24.	Wei S, Cheng X, Li J, et al. Venoarterial extracorporeal membrane oxygenation improves survival in a rat model of acute myocardial infarction. Artif Organs, 2023, 47(7): 1163-1173.
25.	蔡黎明, 张巧妮, 李勇男, 等. 无血预充大鼠外周静脉-动脉体外膜氧合模型建立的初步探索. 中国体外循环杂志, 2019, 17(6): 360-363.
26.	Zazzeron L, Fischbach A, Franco W, et al. Phototherapy and extracorporeal membrane oxygenation facilitate removal of carbon monoxide in rats. Sci Transl Med, 2019, 11(513): eaau4217.
27.	Fujii Y, Sumikura H, Nagahama D. Establishment of a novel miniature veno-venous extracorporeal membrane oxygenation model in the rat. Artif Organs, 2021, 45(1): 63-67.
28.	Li Y, Huang J, Zhang R, et al. Establishment of a venovenous extracorporeal membrane oxygenation in a rat model of acute respiratory distress syndrome. Perfusion, 2023, 38(1): 85-91.
29.	Zhang R, Zhai K, Huang J, et al. Sevoflurane alleviates lung injury and inflammatory response compared with propofol in a rat model of VV ECMO. Perfusion, 2024, 39(1):142-150.
30.	Huang J, Zhang R, Zhai K, et al. Venovenous extracorporeal membrane oxygenation promotes alveolar epithelial recovery by activating Hippo/YAP signaling after lung injury. J Heart Lung Transplant, 2022, 41(10): 1391-1400.
31.	纪振华, 武婷. 离心泵体外循环的应用进展. 天津医药, 2019, 47(10): 1117-1120.
32.	Etchill EW, Dante SA, Garcia AV. Extracorporeal membrane oxygenation in the pediatric population: Who should go on, and who should not. Curr Opin Pediatr, 2020, 32(3): 416-423.
33.	Wang H, Chen F, Li J, et al. Vaspin antagonizes high fat-induced bone loss in rats and promotes osteoblastic differentiation in primary rat osteoblasts through Smad-Runx2 signaling pathway. Nutr Metab (Lond), 2020, 17: 9.
34.	Chlebowski MM, Baltagi S, Carlson M, et al. Clinical controversies in anticoagulation monitoring and antithrombin supplementation for ECMO. Crit Care, 2020, 24(1): 19.
35.	Djordjevic I, Liakopoulos O, Elskamp M, et al. Concomitant intra-aortic balloon pumping significantly reduces left ventricular pressure during central veno-arterial extracorporeal membrane oxygenation: Results from a large animal model. Life (Basel), 2022, 12(11): 1859.

1. Li ZJ, Zhang DF, Zhang WH. Analysis of nosocomial infection and risk factors in patients with ECMO treatment. Infect Drug Resist, 2021, 14: 2403-2410.
2. Mahmoud AA, Avedissian SN, Al-Qamari A, et al. Pharmacokinetic assessment of pre- and post-oxygenator vancomycin concentrations in extracorporeal membrane oxygenation: A prospective observational study. Clin Pharmacokinet, 2020, 59(12): 1575-1587.
3. Pequignot B, Lescroart M, Orlowski S, et al. Methylene blue reduces fluid loading and norepinephrine requirements for post-resuscitation syndrome in a pig model of refractory cardiac arrest resuscitated with veno-arterial ECMO. J Clin Med, 2022, 11(9): 2515.
4. Qi J, Gao S, Liu G, et al. An ovine model of awake veno-arterial extracorporeal membrane oxygenation. Front Vet Sci, 2021, 8: 809487.
5. Tweddell JS, Kharnaf M, Zafar F, et al. Targeting the contact system in a rabbit model of extracorporeal membrane oxygenation. Blood Adv, 2023, 7(8): 1404-1417.
6. 薛平菲, 于洁, 黑飞龙. 大鼠静脉-动脉体外膜氧合模型研究进展. 中国体外循环杂志, 2019, 17(5): 318-320.
7. 陈原森, 刘子泉, 王海旺, 等. 大鼠体外膜肺氧合设备的研制与模型应用. 中华灾害救援医学, 2021, 9(8): 1171-1175.
8. Juhl L, Petersen KA, Larsen EH, et al. The in vivo effect of adrenomedullin on rat dural and pial arteries. Eur J Pharmacol, 2006, 538(1-3): 101-107.
9. Janata A, Drabek T, Magnet IA, et al. Extracorporeal versus conventional cardiopulmonary resuscitation after ventricular fibrillation cardiac arrest in rats: A feasibility trial. Crit Care Med, 2013, 41(9): e211-e222.
10. Chang RW, Luo CM, Yu HY, et al. Investigation of the pathophysiology of cardiopulmonary bypass using rodent extracorporeal life support model. BMC Cardiovasc Disord, 2017, 17(1): 123.
11. Ahmed N, Laghari AH, AlBkhoor B, et al. Fingolimod plays role in attenuation of myocardial injury related to experimental model of cardiac arrest and extracorporeal life support resuscitation. Int J Mol Sci, 2019, 20(24): 6237.
12. 于洁, 薛平菲, 陈书弘, 等. 大鼠体外心肺复苏模型的建立与评价. 中国体外循环杂志, 2020, 18(1): 44-47.
13. 薛平菲, 于洁, 秦春妮, 等. 无血预充大鼠体外心肺复苏模型的建立及支持效果评价. 中国分子心脏病学杂志, 2021, 21(1): 3748-3752.
14. 陈燕桦, 张炳东, 梁东科, 等. 体外膜肺氧合对急性肺损伤治疗的实验研究. 中国现代医学杂志, 2011, 21(19): 2215-2218.
15. Ali AA, Downey P, Singh G, et al. Rat model of veno-arterial extracorporeal membrane oxygenation. J Transl Med, 2014, 12: 37.
16. Fujii Y, Tatsumi E, Nakamura F, et al. PaO₂ greater than 300 mm Hg promotes an inflammatory response during extracorporeal circulation in a rat extracorporeal membrane oxygenation model. J Thorac Dis, 2020, 12(3): 749-757.
17. Edinger F, Schneck E, Schulte C, et al. Comparison of the effect of membrane sizes and fibre arrangements of two membrane oxygenators on the inflammatory response, oxygenation and decarboxylation in a rat model of extracorporeal membrane oxygenation. BMC Cardiovasc Disord, 2020, 20(1): 294.
18. Edinger F, Schmitt C, Koch C, et al. Application of alpha1-antitrypsin in a rat model of veno-arterial extracorporeal membrane oxygenation. Sci Rep, 2021, 11(1): 15849.
19. Fujii Y, Abe T, Ikegami K. Diabetic pathophysiology enhances inflammation during extracorporeal membrane oxygenation in a rat model. Membranes (Basel), 2021, 11(4): 283.
20. Umei N, Lai A, Miller J, et al. Establishment and evaluation of a rat model of extracorporeal membrane oxygenation (ECMO) thrombosis using a 3D-printed mock-oxygenator. J Transl Med, 2021, 19(1): 179.
21. Xing Y, Cheng D, Shi C, et al. The protective role of YTHDF1-knock down macrophages on the immune paralysis of severe sepsis rats with ECMO. Microvasc Res, 2021, 137: 104178.
22. Cheng X, Zhang R, Wei S, et al. Dexamethasone alleviates myocardial injury in a rat model of acute myocardial infarction supported by venoarterial extracorporeal membrane oxygenation. Front Public Health, 2022, 10: 900751.
23. Edinger F, Schneck E, Schulte C, et al. Impact of the inspiratory oxygen fraction on the cardiac output during jugulo-femoral venoarterial extracorporeal membrane oxygenation in the rat. BMC Cardiovasc Disord, 2022, 22(1): 174.
24. Wei S, Cheng X, Li J, et al. Venoarterial extracorporeal membrane oxygenation improves survival in a rat model of acute myocardial infarction. Artif Organs, 2023, 47(7): 1163-1173.
25. 蔡黎明, 张巧妮, 李勇男, 等. 无血预充大鼠外周静脉-动脉体外膜氧合模型建立的初步探索. 中国体外循环杂志, 2019, 17(6): 360-363.
26. Zazzeron L, Fischbach A, Franco W, et al. Phototherapy and extracorporeal membrane oxygenation facilitate removal of carbon monoxide in rats. Sci Transl Med, 2019, 11(513): eaau4217.
27. Fujii Y, Sumikura H, Nagahama D. Establishment of a novel miniature veno-venous extracorporeal membrane oxygenation model in the rat. Artif Organs, 2021, 45(1): 63-67.
28. Li Y, Huang J, Zhang R, et al. Establishment of a venovenous extracorporeal membrane oxygenation in a rat model of acute respiratory distress syndrome. Perfusion, 2023, 38(1): 85-91.
29. Zhang R, Zhai K, Huang J, et al. Sevoflurane alleviates lung injury and inflammatory response compared with propofol in a rat model of VV ECMO. Perfusion, 2024, 39(1):142-150.
30. Huang J, Zhang R, Zhai K, et al. Venovenous extracorporeal membrane oxygenation promotes alveolar epithelial recovery by activating Hippo/YAP signaling after lung injury. J Heart Lung Transplant, 2022, 41(10): 1391-1400.
31. 纪振华, 武婷. 离心泵体外循环的应用进展. 天津医药, 2019, 47(10): 1117-1120.
32. Etchill EW, Dante SA, Garcia AV. Extracorporeal membrane oxygenation in the pediatric population: Who should go on, and who should not. Curr Opin Pediatr, 2020, 32(3): 416-423.
33. Wang H, Chen F, Li J, et al. Vaspin antagonizes high fat-induced bone loss in rats and promotes osteoblastic differentiation in primary rat osteoblasts through Smad-Runx2 signaling pathway. Nutr Metab (Lond), 2020, 17: 9.
34. Chlebowski MM, Baltagi S, Carlson M, et al. Clinical controversies in anticoagulation monitoring and antithrombin supplementation for ECMO. Crit Care, 2020, 24(1): 19.
35. Djordjevic I, Liakopoulos O, Elskamp M, et al. Concomitant intra-aortic balloon pumping significantly reduces left ventricular pressure during central veno-arterial extracorporeal membrane oxygenation: Results from a large animal model. Life (Basel), 2022, 12(11): 1859.

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