Intra-pulmonary Artery Infusion of Antitumor Necrosis Factor-α Antibody Attenuates Lung Injury after Cardiopu-lmonary Bypass_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

YU Yang , GAO Mingxin , LI Haitao , ZHANG Fan , BAI Chen , GU Chengxiong.

Department of Cardiac　Surgery，Beijing An Zhen Hospital，Capital Medical University，Beijing 100029，P. R. China;

Corresponding author：

Keywords：

体外循环; 　肺损伤; 　细胞凋亡; 　抗肿瘤坏死因子抗体

DOI：

10.7507/1007-4848.20130214

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the protective effects of antitumor necrosis factor-α antibody （TNF-αAb） on lung injury after cardiopulmonary bypass （CPB） and their mechanisms. Methods Forty healthy New Zealand white rabbits，weighting 2.0-2.5 kg，male or female，were randomly divided into 4 groups with 10 rabbits in each group. In groupⅠ，the rabbits received CPB and pulmonary arterial perfusion. In group Ⅱ，the rabbits received CPB and pulmonary arterial perfusion with TNF-αAb. In group Ⅲ，the rabbits received CPB only. In group Ⅳ，the rabbits only received sham surgery. Neutrophils count，TNF-α and malondialdehyde （MDA） concentrations of the blood samples from the left and right atrium as well as oxygenation index were examined before and after CPB in the 4 groups. Pathological and ultrastructural changes of the lung tissues were observed under light and electron microscopes. Lung water content，TNF-α mRNA and apoptoticindex of the lung tissues were measured at different time points. Results Compared with group Ⅳ，after CPB，the rabbitsin group Ⅰ to group Ⅲ showed significantly higher blood levels of neutrophils count，TNF-α and MDA（P＜0.05），higherTNF-α mRNA expression，apoptosis index and water content of the lung tissues （P＜0.05），and significantly lower oxyg-enation index （P＜0.05） as well as considerable pathomorphological changes in the lung tissues. Compared with group Ⅱ，after CPB，the rabbits in groups Ⅰ and Ⅲ had significantly higher blood concentrations of TNF-α （5 minutes after aortic declamping，220.43±16.44 pg/ml vs.185.27±11.78 pg/ml，P＜0.05；249.99±14.09 pg/ml vs.185.27±11.78 pg/ml，P＜0.05），significantly higher apoptosis index （at the time of CPB termination，60.7‰±13.09‰ vs. 37.9‰±7.78‰，P＜0.05；59.6‰±7.74‰ vs. 37.9‰±7.78‰，P＜0.05），significantly higher blood levels of neutrophils count and MDA （P＜0.05），significantly higher TNF-α mRNA expression and water content of the lung tissues （P＜0.05），and significantly loweroxygenation index （P＜0.05） as well as considerable pathomorphological changes in the lung tissues. Compared with groupⅠ，rabbits in group Ⅲ had significantly higher above parameters （P＜0.05） but lower oxygenation index （P＜0.05） only at 30 minutes after the start of CPB. Conclusion Pulmonary artery perfusion with TNF-αAb can significantly attenuate inflammatory lung injury and apoptosis of the lung tissues during CPB.

Citation： YU Yang,GAO Mingxin,LI Haitao,ZHANG Fan,BAI Chen,GU Chengxiong.. Intra-pulmonary Artery Infusion of Antitumor Necrosis Factor-α Antibody Attenuates Lung Injury after Cardiopu-lmonary Bypass. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2013, 20(6): 698-704. doi: 10.7507/1007-4848.20130214 Copy

1.	Rong J， Ye S， Liang MY， et al. Receptor for advanced glycation end products involved in lung ischemia reperfusion injury in cardiopulmonary bypass attenuated by controlled oxygen reperfusion in a canine model. ASAIO J， 2013， 59 （3）：302-308.
2.	Luan ZG， Zhang J， Yin XH， et al. Ethyl pyruvate significantly inhibits tumour necrosis factor-α， interleukin-1β and high mobility group box 1 releasing and attenuates sodium taurocholate-induced severe acute pancreatitis associated with acute lung injury. Clin Exp Immunol， 2013， 172 （3）：417-426.
3.	Klass O， Fischer UM， Antonyan A， et al. Pneumocyte apoptosis induction during cardiopulmonary bypass：effective prevention by radical scavenging using N-acetylcysteine. J Invest Surg， 2007， 20 （6）：349-356.
4.	于洋，叶明，夏求明．兔体外循环模型的建立．中国胸心血管外科临床杂志， 2003， 10 （2）：151-152．.
5.	Santini F， Onorati F， Telesca M， et al. Selective pulmonary pulsatileperfusion with oxygenated blood during cardiopulmonary bypass attenuates lung tissue inflammation but does not affect circulatingcytokine levels. Eur J Cardiothorac Surg， 2012， 42 （6）：942 - 950.
6.	Sewing AC， Kantores C， Ivanovska J， et al. Therapeutic hypercapniaprevents bleomycin-induced pulmonary hypertension in neonatal rats by limiting macrophage-derived tumor necrosis factor-α. Am J Physiol Lung Cell Mol Physiol， 2012， 303 （1）：75-87.
7.	张根成，汪曾炜，易定华，等．离体兔肺缺血再灌注损伤肺表面活性蛋白变化及保护．中国胸心血管外科临床杂志， 2000， 7 （2）：109-112．.
8.	Wang C， Li D， Qian Y， et al. Increased matrix metalloproteinase-9 activity and mRNA expression in lung injury following cardiopulmonary bypass. Lab Invest， 2012， 92 （6）：910-916.
9.	Li T， Luo N， Du L， et al. Early and marked up-regulation of TNF-α in acute respiratory distress syndrome after cardiopulmonary bypass. Front Med， 2012， 6 （3）：296-301.
10.	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.
11.	Paparella D， Scrascia G， Rotunno C， et al. A biocompatible cardio-pulmonary bypass strategy to reduce hemostatic and inflammatoryalterations：a randomized controlled trial. J Cardiothorac VascAnesth， 2012， 26 （4）：557-562.
12.	Masuda K， Ripley B， Nishimura R， et al. Arid5a controls IL-6 mRNA stability， which contributes to elevation of IL-6 level in vivo. Proc Natl Acad Sci U S A， 2013， 110 （23）：9409-9414.
13.	Zheng ZK， Wang JJ， Hu H， et al. Short-term inhalation of nitric oxide inhibits activations of toll-like receptor 2 and 4 in the lung after ischemia-reperfusion injury in mice. J Huazhong Univ Sci Technolog Med Sci， 2013， 33 （2）：219-223.
14.	Heeba GH， Mahmoud ME， El Hanafy AA. Anti-inflammatory potential of curcumin and quercetin in rats：Role of oxidative stress， heme oxygenase-1 and TNF-α. Toxicol Ind Health， 2012， [Epub ahead of print].
15.	闫炀，闫路勤，耿希刚．无肝素化体外循环转流及早期炎性因子的表达．中国胸心血管外科临床杂志， 2012， 19 （4）：414-418．.
16.	Hilgendorf KI， Leshchiner ES， Nedelcu S， et al. The retinoblastoma protein induces apoptosis directly at the mitochondria. Genes Dev， 2013， 27 （9）：1003-1015.
17.	Goebel U， Siepe M， Mecklenburg A， et al. Reduced pulmonary inflammatory response during cardiopulmonary bypass：effects of combined pulmonary perfusion and carbon monoxide inhalation. Eur J Cardiothorac Surg， 2008 ， 34 （6）：1165-1172.
18.	Herold S， Ludwig S， Pleschka S， et al. Apoptosis signaling in infl-uenza virus propagation， innate host defense， and lung injury. J LeukocBiol， 2012， 92 （1）：75 – 82.
19.	Veltkamp C， Anstaett M， Wahl K， et al. Apoptosis of regulatory T lymphocytes is increased in chronic inflammatory bowel disease and reversed by anti-TNFα treatment . Gut， 2011， 60 （10）：1345-1353.
20.	Kearney CJ， Sheridan C， Cullen SP， et al. Inhibitor of apoptosisproteins （IAPs） and their antagonists regulate spontaneous and tumornecrosis factor （TNF）-induced proinflammatory cytokine and chemo-kine production. J Biol Chem， 2013， 288 （7）：4878-4890.
21.	Hindryckx P， De Vos M， Jacques P， et al. Hydroxylase inhibition abrogates TNF-alpha-induced intestinal epithelial damage by hypoxia- inducible factor-1-dependent repression of FADD. J Immunol， 2010， 185 （10）：6306-6316.
22.	Delmotte P， Yang B， Thompson MA， et al. Inflammation alters regional mitochondrial Ca?＋ in human airway smooth muscle cells. Am J Physiol Cell Physiol， 2012， 303 （3）：244-256.
23.	Maniatis NA， Kardara M， Hecimovich D， et al. Role of caveolin-1 expression in the pathogenesis of pulmonary edema in ventilator-induced lung injury. Pulm Circ， 2012， 2 （4）：452-460.
24.	Radovits T， Beller CJ， Groves JT， et al. Effects of FP15， a peroxynitrite decomposition catalyst on cardiac and pulmonary function after cardiopulmonary bypass. Eur J Cardiothorac Surg， 2012， 41 （2）：391 - 396.

1. 　Rong J， Ye S， Liang MY， et al. Receptor for advanced glycation end products involved in lung ischemia reperfusion injury in cardiopulmonary bypass attenuated by controlled oxygen reperfusion in a canine model. ASAIO J， 2013， 59 （3）：302-308.
2. 　Luan ZG， Zhang J， Yin XH， et al. Ethyl pyruvate significantly inhibits tumour necrosis factor-α， interleukin-1β and high mobility group box 1 releasing and attenuates sodium taurocholate-induced severe acute pancreatitis associated with acute lung injury. Clin Exp Immunol， 2013， 172 （3）：417-426.
3. 　Klass O， Fischer UM， Antonyan A， et al. Pneumocyte apoptosis induction during cardiopulmonary bypass：effective prevention by radical scavenging using N-acetylcysteine. J Invest Surg， 2007， 20 （6）：349-356.
4. 　于洋，叶明，夏求明．兔体外循环模型的建立．中国胸心血管外科临床杂志， 2003， 10 （2）：151-152．.
5. 　Santini F， Onorati F， Telesca M， et al. Selective pulmonary pulsatileperfusion with oxygenated blood during cardiopulmonary bypass attenuates lung tissue inflammation but does not affect circulatingcytokine levels. Eur J Cardiothorac Surg， 2012， 42 （6）：942 - 950.
6. 　Sewing AC， Kantores C， Ivanovska J， et al. Therapeutic hypercapniaprevents bleomycin-induced pulmonary hypertension in neonatal rats by limiting macrophage-derived tumor necrosis factor-α. Am J Physiol Lung Cell Mol Physiol， 2012， 303 （1）：75-87.
7. 　张根成，汪曾炜，易定华，等．离体兔肺缺血再灌注损伤肺表面活性蛋白变化及保护．中国胸心血管外科临床杂志， 2000， 7 （2）：109-112．.
8. 　Wang C， Li D， Qian Y， et al. Increased matrix metalloproteinase-9 activity and mRNA expression in lung injury following cardiopulmonary bypass. Lab Invest， 2012， 92 （6）：910-916.
9. 　Li T， Luo N， Du L， et al. Early and marked up-regulation of TNF-α in acute respiratory distress syndrome after cardiopulmonary bypass. Front Med， 2012， 6 （3）：296-301.
10. 　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.
11. 　Paparella D， Scrascia G， Rotunno C， et al. A biocompatible cardio-pulmonary bypass strategy to reduce hemostatic and inflammatoryalterations：a randomized controlled trial. J Cardiothorac VascAnesth， 2012， 26 （4）：557-562.
12. 　Masuda K， Ripley B， Nishimura R， et al. Arid5a controls IL-6 mRNA stability， which contributes to elevation of IL-6 level in vivo. Proc Natl Acad Sci U S A， 2013， 110 （23）：9409-9414.
13. 　Zheng ZK， Wang JJ， Hu H， et al. Short-term inhalation of nitric oxide inhibits activations of toll-like receptor 2 and 4 in the lung after ischemia-reperfusion injury in mice. J Huazhong Univ Sci Technolog Med Sci， 2013， 33 （2）：219-223.
14. 　Heeba GH， Mahmoud ME， El Hanafy AA. Anti-inflammatory potential of curcumin and quercetin in rats：Role of oxidative stress， heme oxygenase-1 and TNF-α. Toxicol Ind Health， 2012， [Epub ahead of print].
15. 　闫炀，闫路勤，耿希刚．无肝素化体外循环转流及早期炎性因子的表达．中国胸心血管外科临床杂志， 2012， 19 （4）：414-418．.
16. 　Hilgendorf KI， Leshchiner ES， Nedelcu S， et al. The retinoblastoma protein induces apoptosis directly at the mitochondria. Genes Dev， 2013， 27 （9）：1003-1015.
17. 　Goebel U， Siepe M， Mecklenburg A， et al. Reduced pulmonary inflammatory response during cardiopulmonary bypass：effects of combined pulmonary perfusion and carbon monoxide inhalation. Eur J Cardiothorac Surg， 2008 ， 34 （6）：1165-1172.
18. 　Herold S， Ludwig S， Pleschka S， et al. Apoptosis signaling in infl-uenza virus propagation， innate host defense， and lung injury. J LeukocBiol， 2012， 92 （1）：75 – 82.
19. 　Veltkamp C， Anstaett M， Wahl K， et al. Apoptosis of regulatory T lymphocytes is increased in chronic inflammatory bowel disease and reversed by anti-TNFα treatment . Gut， 2011， 60 （10）：1345-1353.
20. 　Kearney CJ， Sheridan C， Cullen SP， et al. Inhibitor of apoptosisproteins （IAPs） and their antagonists regulate spontaneous and tumornecrosis factor （TNF）-induced proinflammatory cytokine and chemo-kine production. J Biol Chem， 2013， 288 （7）：4878-4890.
21. 　Hindryckx P， De Vos M， Jacques P， et al. Hydroxylase inhibition abrogates TNF-alpha-induced intestinal epithelial damage by hypoxia- inducible factor-1-dependent repression of FADD. J Immunol， 2010， 185 （10）：6306-6316.
22. 　Delmotte P， Yang B， Thompson MA， et al. Inflammation alters regional mitochondrial Ca?＋ in human airway smooth muscle cells. Am J Physiol Cell Physiol， 2012， 303 （3）：244-256.
23. 　Maniatis NA， Kardara M， Hecimovich D， et al. Role of caveolin-1 expression in the pathogenesis of pulmonary edema in ventilator-induced lung injury. Pulm Circ， 2012， 2 （4）：452-460.
24. 　Radovits T， Beller CJ， Groves JT， et al. Effects of FP15， a peroxynitrite decomposition catalyst on cardiac and pulmonary function after cardiopulmonary bypass. Eur J Cardiothorac Surg， 2012， 41 （2）：391 - 396.

Previous Article
Early Prevention of Severe Acute Pancreatitis Complicated with Infection
Next Article
种族对结肠癌患者术后预后的影响

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Intra-pulmonary Artery Infusion of Antitumor Necrosis Factor-α Antibody Attenuates Lung Injury after Cardiopu-lmonary Bypass

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content