The Early Responses of VEGFs During Acute Lung Injury Induced by Immersion in Seawater after Open Chest Trauma_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

HU Xiaohong ^1,2 , LI Yi ³ , XUE Zhiqiang ⁴ , Han Zhihai ³ ,  DUAN Yunyou. ³

Academy of Military Medical Sciences. Beijing, 100850, China Corresponding Author: DUAN Yun-you, E-mail: navy9lemon@ sohu. com;

Corresponding author：

DUAN Yunyou., Email: navy9lemon@sohu.com

Keywords：

Acute lung injury; Seawater; Open chest trauma; Vascular endothelial growth factor; Vascular endothelial growth factor receptor

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【Abstract】Objective To investigate the role of VEGF and its soluble VEGF receptor ( sVEGFR-1) in pathogenesis of acute lung injury ( ALI) induced by immersion in seawater after open chest trauma. Methods Sixteen hybridized adult dogs were randomly divided into control group and seawater group. The control group only suffered from open chest trauma, whereas the seawater group were exposed to seawater after open chest trauma. Blood samples were collected at the 0, 2, 4, 6, 8 h after trauma for measurement of white blood cell count, arterial blood gas, plasma osmotic pressure ( POP) , electrolyte concentration, IL-8, vWF, VEGF and sVEGFR-1 levels. The lungs tissue and BALF was collected at 8 h after trauma. Pathological changes of the lung was observed under light microscope by HE staining. Meanwhile VEGF and sVEGFR-1 levels were measured in BALF and lung tissue homogenate. Total protein concentrations in plasma and BALF were measured to calculate the pulmonary penetration index ( PPI) . Results The lung of the seawater group showed interstitial mononuclear cell and neutrophil infiltration, interstitial edema, and vascular congestion. VEGF and sVEGFR-1 were significantly increased in the plasma, while VEGF was significantly reduced in the lung tissues and BALF. The levels of IL-1β, IL-8 and vWF, just as the level of VEGF, were significantly increased in the plasma. Meanwhile, the POP and electrolyte concentration were significantly increased. In the plasma, the responses of VEGFs during the early onset of ALI induced by immersion in seawater after open chest trauma were consistent with the POP and PPI. Conclusions High plasma levels and low BALF/ lung tissue levels of VEGFs is a distinguishing characteristic during the early onset of ALI induced by immersion in seawater after open chest trauma. VEGF may be a novel biomarker which has an important role in the development of ALI.

Citation： HU Xiaohong,LI Yi,XUE Zhiqiang,Han Zhihai,DUAN Yunyou.. The Early Responses of VEGFs During Acute Lung Injury Induced by Immersion in Seawater after Open Chest Trauma. Chinese Journal of Respiratory and Critical Care Medicine, 2009, 09(5): 482-486. doi: Copy

1.	沈宏亮, 王强. 海水浸泡创伤病理生理变化和救治措施的研究进展. 第二军医大学学报, 2003, 24: 1365-1367.
2.	虞积耀, 赖西南, 李辉, 等. 战伤合并海水浸泡生存时间及死亡率的动物实验研究. 解放军医学杂志, 2005, 30: 268-269.
3.	Ferrara N. Vascular endothelial growth factor and the regulation of angiogenesis. Recent Prog Horm Res, 2000, 55: 15-35.
4.	Thickett DR, Armstrong L, and Millar AB. A role for vascular endothelial growth factor in acute and resolving lung injury. Am J Respir Crit Care Med, 2002 , 166: 1332 -1337 .
5.	Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med, 2003, 9: 669-676.
6.	Tsokos M, Pufe T, Paulsen F, et al. Pulmonary expression of vascular endothelial growth factor in sepsis. Arch Pathol Lab Med, 2003, 127: 331-335.
7.	姜晓晖, 王雪芬, 周永列, 等. 急性肺损伤早期支气管肺泡灌洗液中VEGF 变化的研究. 浙江医学, 2005, 27: 659-661.
8.	孟激光, 段蕴铀, 薛志强, 等. 胸部开放伤后海水灌入胸腔致急性肺损伤犬模型的实验研究. 中华航海医学与高气压医学杂志, 2008, 15: 74-77.
9.	Koyama S, Sato E, Haniuda M, et al. Decreased level of vascular endothelial growth factor in bronchoalveolar lavage fluid of normal smokers and patients with pulmonary fibrosis. Am J Respir Crit Care Med, 2002, 166: 382-385.
10.	Kaner RJ, Crystal RG. Compartmentalization of vascular endothelial growth factor to the epithelial surface of the human lung. Mol Med, 2001, 7: 240-246.
11.	Partovian C, Adnot S, Eddahibi S, et al. Heart and lung VEGF mRNA expression in rate with monocrotaline or hypoxia-induced pulmonary hypertension. Am J Physiol, 1998, 275: H1948-H1956.
12.	Thickett DR, Armstrong L, Christie SJ, et al. Vascular endothelial growth factor may contribute to increased vascular permeability in acute respiratory distress syndrome. Am J Respir Crit Care Med, 2001, 164: 1601-1605.
13.	Maitre B, Boussat S, Jean D, et al. Vascular endothelial growth factor synthesis in the acute phase of experimental and clinical lung injury. Eur Respir J, 2001, 18: 100-106.
14.	Kaner RJ, Ladetto JV, Singh R, et al. Lung overexpression of the vascular endothelial growth factor gene induces pulmonary edema. Am J Respir Cell Mol Biol, 2000, 22: 657-664.
15.	Mura M, dos Santos CC, Stewart D, et al. Vascular endothelial growth factor and related molecules in acute lung injury. J Appl Physiol, 2004, 97: 1605-1617.
16.	Fehrenbach A, Pufe T, Wittwer T, et al. Reduced vascular endothelial growth factor correlates with alveolar epithelial damage after experimental ischemia and reperfusion. J Heart Lung Transplant, 2003, 22: 967-978.
17.	Koehne P, Willam C, Strauss E, et, al. Lack of hypoxic stimulation of VEGF secretion from neutrophils and platelets. Am J Physiol Heart Circ Physiol, 2000, 279: H817-H824.
18.	Haddad el-B, McCluskie K, Birrell MA, et al. Differential effects of ebselen on neutrophil recruitment, chemokine, and inflammatory mediator expression in a rat model of lipopolysaccharide-induced pulmonary inflammation. J Immunol, 2002, 169: 974-982.
19.	Mukaida N. Pathophysiological roles of interleukin-8 / CXCL8 in pulmonary diseases. Am J Physiol Lung Cell Mol Physiol, 2003 , 284: L566-L577.
20.	Shames BD, Zallen GS, McIntyre RC Jr, et al. Chemokines as mediators of diseases related to surgical conditions. Shock, 2000,14: 1.
21.	Riffo-Vasquez Y, Spina D. Role of cytokines and chemokines in bronchial hyperresponsiveness and airway inflammation. Pharmacol Ther, 2002, 94: 185-211.
22.	Varol E, Ozaydin M, Sahin M, et al. vWf levels as a circulating marker of endothelial dysfunction in patients with hypertrophic cardiomyopathy. Indian Heart J, 2005, 57: 655-657.

1. 沈宏亮, 王强. 海水浸泡创伤病理生理变化和救治措施的研究进展. 第二军医大学学报, 2003, 24: 1365-1367.
2. 虞积耀, 赖西南, 李辉, 等. 战伤合并海水浸泡生存时间及死亡率的动物实验研究. 解放军医学杂志, 2005, 30: 268-269.
3. Ferrara N. Vascular endothelial growth factor and the regulation of angiogenesis. Recent Prog Horm Res, 2000, 55: 15-35.
4. Thickett DR, Armstrong L, and Millar AB. A role for vascular endothelial growth factor in acute and resolving lung injury. Am J Respir Crit Care Med, 2002 , 166: 1332 -1337 .
5. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med, 2003, 9: 669-676.
6. Tsokos M, Pufe T, Paulsen F, et al. Pulmonary expression of vascular endothelial growth factor in sepsis. Arch Pathol Lab Med, 2003, 127: 331-335.
7. 姜晓晖, 王雪芬, 周永列, 等. 急性肺损伤早期支气管肺泡灌洗液中VEGF 变化的研究. 浙江医学, 2005, 27: 659-661.
8. 孟激光, 段蕴铀, 薛志强, 等. 胸部开放伤后海水灌入胸腔致急性肺损伤犬模型的实验研究. 中华航海医学与高气压医学杂志, 2008, 15: 74-77.
9. Koyama S, Sato E, Haniuda M, et al. Decreased level of vascular endothelial growth factor in bronchoalveolar lavage fluid of normal smokers and patients with pulmonary fibrosis. Am J Respir Crit Care Med, 2002, 166: 382-385.
10. Kaner RJ, Crystal RG. Compartmentalization of vascular endothelial growth factor to the epithelial surface of the human lung. Mol Med, 2001, 7: 240-246.
11. Partovian C, Adnot S, Eddahibi S, et al. Heart and lung VEGF mRNA expression in rate with monocrotaline or hypoxia-induced pulmonary hypertension. Am J Physiol, 1998, 275: H1948-H1956.
12. Thickett DR, Armstrong L, Christie SJ, et al. Vascular endothelial growth factor may contribute to increased vascular permeability in acute respiratory distress syndrome. Am J Respir Crit Care Med, 2001, 164: 1601-1605.
13. Maitre B, Boussat S, Jean D, et al. Vascular endothelial growth factor synthesis in the acute phase of experimental and clinical lung injury. Eur Respir J, 2001, 18: 100-106.
14. Kaner RJ, Ladetto JV, Singh R, et al. Lung overexpression of the vascular endothelial growth factor gene induces pulmonary edema. Am J Respir Cell Mol Biol, 2000, 22: 657-664.
15. Mura M, dos Santos CC, Stewart D, et al. Vascular endothelial growth factor and related molecules in acute lung injury. J Appl Physiol, 2004, 97: 1605-1617.
16. Fehrenbach A, Pufe T, Wittwer T, et al. Reduced vascular endothelial growth factor correlates with alveolar epithelial damage after experimental ischemia and reperfusion. J Heart Lung Transplant, 2003, 22: 967-978.
17. Koehne P, Willam C, Strauss E, et, al. Lack of hypoxic stimulation of VEGF secretion from neutrophils and platelets. Am J Physiol Heart Circ Physiol, 2000, 279: H817-H824.
18. Haddad el-B, McCluskie K, Birrell MA, et al. Differential effects of ebselen on neutrophil recruitment, chemokine, and inflammatory mediator expression in a rat model of lipopolysaccharide-induced pulmonary inflammation. J Immunol, 2002, 169: 974-982.
19. Mukaida N. Pathophysiological roles of interleukin-8 / CXCL8 in pulmonary diseases. Am J Physiol Lung Cell Mol Physiol, 2003 , 284: L566-L577.
20. Shames BD, Zallen GS, McIntyre RC Jr, et al. Chemokines as mediators of diseases related to surgical conditions. Shock, 2000,14: 1.
21. Riffo-Vasquez Y, Spina D. Role of cytokines and chemokines in bronchial hyperresponsiveness and airway inflammation. Pharmacol Ther, 2002, 94: 185-211.
22. Varol E, Ozaydin M, Sahin M, et al. vWf levels as a circulating marker of endothelial dysfunction in patients with hypertrophic cardiomyopathy. Indian Heart J, 2005, 57: 655-657.

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