Large Tidal Volume Mechanical Ventilation Aggravates Acute Lung Injury and Protective Effects of Glutamine_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

LI Jinming , SUN Baojun , YU Senyang , LIU Qinghui.

Department of Respiratory Medicine,The General Hospital of PLA. Beijing, 100853, ChinaCorresponding Author: YU Sen-yang, E-mail: senyangyu@ sina. com;

Corresponding author：

Keywords：

Mechanical ventilation; Lipopolysaccharide; Lung injury; Glutamine

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Objective To study the effects of two different tidal volume mechanical ventilation on lipopolysaccharide( LPS) -induced acute lung injury( ALI) , and explore the effects of glutamine on ALI.Methods Thirty male Sprague-Dawley rats were randomly divided into three groups. After anesthesia and tracheotomy were performed, the rats were challenged with intratracheal LPS ( 5mg/kg) and received ventilation for 4 hours with small animal ventilator. Group A received conventional tidal volume, while group
B received large tidal volume. Group C received large tidal volume as well, with glutamine injected intravenously 1 hour before ventilation. Arterial blood gases were measured every one hour. 4 hours later, the rats were killed by carotid artery bleeding. The total lung wetweightwas measured and lung coefficient ( total lung wet weight /body weight ×100) was counted. WBCs and neutrophils in BALF were counted. Protein concentration, TNF-α, IL-6, and cytokine-induced neutrophil chemoattractant-1 ( CINC-1) levels in BALF,myeloperoxidase ( MPO) , and superoxide dismutase ( SOD) levels in the lung were assayed respectively.Results PaO2 and SOD levels decreased more significantly in group B than those of group A. The lung coefficient, WBCs, neutrophils, protein, TNF-α, IL-6, and CINC-1 levels in BALF, MPO levels in lung increased more significantly in group B than those of group A. PaO2 and SOD levels were significantly higher in group C than those of group B. The lung coefficient, WBCs, neutrophils, protein, TNF-α, IL-6, and CINC-1 levels in BALF,MPO levels in lung were significantly lower in group C than those of group B. Conclusion Large tidal volume mechanical ventilation aggravates LPS-induced ALI, and glutamine has obviously
protective effects.

Citation： LI Jinming,SUN Baojun,YU Senyang,LIU Qinghui.. Large Tidal Volume Mechanical Ventilation Aggravates Acute Lung Injury and Protective Effects of Glutamine. Chinese Journal of Respiratory and Critical Care Medicine, 2010, 9(2): 168-171. doi: Copy

1.	Caruso P. Ventilator-induced lung injury distribution: the key to understanding injury mechanisms. Am J Respir Crit Care Med,2007, 175 : 95-96.
2.	Belperio JA, Keane MP, Lynch JP 3rd, et al. The role of cytokines during the pathogenesis of ventilator-associated and ventilatorinduced lung injury. Semin Respir Crit Care Med, 2006 , 27: 350 -364 .
3.	Halbertsma FJ, Vaneker M, Scheffer GJ, et al. Cytokines and biotrauma in ventilator-induced lung injury: a critical review of the literature. Neth J Med, 2005, 63 : 382-392.
4.	Lee WL, Slutsky AS. Ventilator-induced lung injury and recommendations for mechanical ventilation of patients with ARDS.Semin Respir Crit Care Med, 2001 , 22: 269 -280.
5.	刘晓青, 钟南山, 江华. 谷氨酰胺是否有双相免疫调节作用: 研究证据分析. 中国临床营养杂志, 2003 , 11: 133-135.
6.	Yeh CC, Kao SJ, Lin CC, et al. The immunomodulation of endotoxininduced acute lung injury by hesperidin in vivo and in vitro. Life Sci, 2007, 80: 1821-1831.
7.	Su CF, Yang FL, Chen HI. Inhibition of inducible nitric oxide synthase attenuates acute endotoxin-induced lung injury in rats. Clin Exp Pharmacol Physiol, 2007 , 34: 339-346.
8.	武庆平, 刘萍, 王立奎, 等. 不同潮气量通气对大鼠呼吸机相关性肺损伤模型的影响. 华中科技大学学报( 医学版) , 2006, 35 :511-514.
9.	刘庆辉, 俞森洋. 乙酰半胱氨酸对通气机所致大鼠肺损伤的保护作用. 中国呼吸与危重监护杂志, 2002, 1: 23-26.
10.	连宁芳, 朱蕾. 机械通气的并发症. 中国呼吸与危重监护杂志,2004, 3: 144 -146.
11.	Ramos CD, Heluy-Neto NE, Ribeiro RA, et al. Neutrophil migration induced by IL-8-activated mast cells is mediated by CINC-1 .Cytokine, 2003 , 21: 214-223.
12.	Lorenzetti BB, Veiga FH, Canetti CA, et al. Cytokine-induced neutrophil chemoattractant 1 ( CINC-1 ) mediates the sympathetic component of inflammatory mechanical hypersensitivitiy in rats. Eur Cytokine Netw, 2002 , 13 : 456-461.
13.	Kupczyk M, Bocheńska-Marciniak M, Górski P, et al.Myeloperoxidase ( MPO) as a marker of neutrophil influx into nasalmucosa after recombinant IL-8 challenge. Pneumonol Alergol Pol,2002, 70: 544-549 .
14.	谢继青, 李玉华, 杨春梅, 等. 超氧化物歧化酶的药理作用. 中国生化药物杂志, 2009, 30: 72 -75 .
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16.	Ravagnan L, Gurbuxani S, Susin SA, et al. Heat-shock protein 70 antagonizes apoptosis-inducing factor. Nat Cell Biol, 2001, 3: 839 -843.
17.	Vreugdenhil HA, Haitsma JJ, Jansen KJ, et al. Ventilator-induced heat shock protein 70 and cytokine mRNA expression in a model of lipopolysaccharide-induced lung inflammation. Intensive Care Med,2003, 29: 915-922 .
18.	Amores-Sánchez MI, Medina MA. Glutamine, as a precursor of glutathione, and oxidative stress. Mol Genet Metab, 1999, 67: 100 -105.
19.	Spittler A, Winkler S, G tzinger P, et al. Influence of glutamine on the phenotype and function of human monocytes. Blood, 1995, 86 :1564-1569.
20.	Furukawa S, Saito H, Inoue T, et al. Supplemental glutamine augments phagocytosis and reactive oxygen intermediate production by neutrophils and monocytes from postoperative patients in vitro.Nutrition, 2000, 16: 323-329.
21.	Wallin RP, Lundqvist A, MoréSH, et al. Heat-shock proteins as activators of the innate immune system. Trends Immunol, 2002, 23 :130-135.

1. Caruso P. Ventilator-induced lung injury distribution: the key to understanding injury mechanisms. Am J Respir Crit Care Med,2007, 175 : 95-96.
2. Belperio JA, Keane MP, Lynch JP 3rd, et al. The role of cytokines during the pathogenesis of ventilator-associated and ventilatorinduced lung injury. Semin Respir Crit Care Med, 2006 , 27: 350 -364 .
3. Halbertsma FJ, Vaneker M, Scheffer GJ, et al. Cytokines and biotrauma in ventilator-induced lung injury: a critical review of the literature. Neth J Med, 2005, 63 : 382-392.
4. Lee WL, Slutsky AS. Ventilator-induced lung injury and recommendations for mechanical ventilation of patients with ARDS.Semin Respir Crit Care Med, 2001 , 22: 269 -280.
5. 刘晓青, 钟南山, 江华. 谷氨酰胺是否有双相免疫调节作用: 研究证据分析. 中国临床营养杂志, 2003 , 11: 133-135.
6. Yeh CC, Kao SJ, Lin CC, et al. The immunomodulation of endotoxininduced acute lung injury by hesperidin in vivo and in vitro. Life Sci, 2007, 80: 1821-1831.
7. Su CF, Yang FL, Chen HI. Inhibition of inducible nitric oxide synthase attenuates acute endotoxin-induced lung injury in rats. Clin Exp Pharmacol Physiol, 2007 , 34: 339-346.
8. 武庆平, 刘萍, 王立奎, 等. 不同潮气量通气对大鼠呼吸机相关性肺损伤模型的影响. 华中科技大学学报( 医学版) , 2006, 35 :511-514.
9. 刘庆辉, 俞森洋. 乙酰半胱氨酸对通气机所致大鼠肺损伤的保护作用. 中国呼吸与危重监护杂志, 2002, 1: 23-26.
10. 连宁芳, 朱蕾. 机械通气的并发症. 中国呼吸与危重监护杂志,2004, 3: 144 -146.
11. Ramos CD, Heluy-Neto NE, Ribeiro RA, et al. Neutrophil migration induced by IL-8-activated mast cells is mediated by CINC-1 .Cytokine, 2003 , 21: 214-223.
12. Lorenzetti BB, Veiga FH, Canetti CA, et al. Cytokine-induced neutrophil chemoattractant 1 ( CINC-1 ) mediates the sympathetic component of inflammatory mechanical hypersensitivitiy in rats. Eur Cytokine Netw, 2002 , 13 : 456-461.
13. Kupczyk M, Bocheńska-Marciniak M, Górski P, et al.Myeloperoxidase ( MPO) as a marker of neutrophil influx into nasalmucosa after recombinant IL-8 challenge. Pneumonol Alergol Pol,2002, 70: 544-549 .
14. 谢继青, 李玉华, 杨春梅, 等. 超氧化物歧化酶的药理作用. 中国生化药物杂志, 2009, 30: 72 -75 .
15. Mosser DD, Caron AW, Bourget L, et al. The chaperone function of hsp70 is required for protection against stress-induced apoptosis.Mol Cell Biol, 2000, 20: 7146-7159.
16. Ravagnan L, Gurbuxani S, Susin SA, et al. Heat-shock protein 70 antagonizes apoptosis-inducing factor. Nat Cell Biol, 2001, 3: 839 -843.
17. Vreugdenhil HA, Haitsma JJ, Jansen KJ, et al. Ventilator-induced heat shock protein 70 and cytokine mRNA expression in a model of lipopolysaccharide-induced lung inflammation. Intensive Care Med,2003, 29: 915-922 .
18. Amores-Sánchez MI, Medina MA. Glutamine, as a precursor of glutathione, and oxidative stress. Mol Genet Metab, 1999, 67: 100 -105.
19. Spittler A, Winkler S, G tzinger P, et al. Influence of glutamine on the phenotype and function of human monocytes. Blood, 1995, 86 :1564-1569.
20. Furukawa S, Saito H, Inoue T, et al. Supplemental glutamine augments phagocytosis and reactive oxygen intermediate production by neutrophils and monocytes from postoperative patients in vitro.Nutrition, 2000, 16: 323-329.
21. Wallin RP, Lundqvist A, MoréSH, et al. Heat-shock proteins as activators of the innate immune system. Trends Immunol, 2002, 23 :130-135.

Chinese Journal of Respiratory and Critical Care Medicine

Large Tidal Volume Mechanical Ventilation Aggravates Acute Lung Injury and Protective Effects of Glutamine

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