大白鼠无心跳供体（NHBD）肺移植的实验研究
|
摘要
目的：探讨不同热缺血时间对无心跳供体肺的结构和功能的影响，以进一步论证无心跳供体肺应用于肺移植的可能性。
方法：取30对健康Sprague-Dawley大白鼠，即供体和受体，分成3组，即有心跳供体(HBD)组、无心跳供体—热缺血30分钟(NHBD-30)组、无心跳供体—热缺血60分钟(NHBD-60)组。3组均给予气管切开，连接呼吸机辅助呼吸，吸气氧浓度50％。供体鼠处死的方法均为剪断腹主动脉放血，HBD组供体在处死的同时灌注4℃LPD液，NHBD-30组、NHBD组供体处死后维持辅助呼吸，分别放置室温中30分钟或60分钟，再灌注低钾右旋糖苷(LPD)液。供肺置于4℃LPD液中4小时，留取左肺。受体鼠切除左肺，行“原位左肺移植术”。术后维持辅助呼吸1小时，经右侧进胸，阻断右肺门，测定观测指标。
结果：1．阻断右肺门后，HBD组、NHBD-30组存活时间均超过30分钟，NHBD-60组有4只10分钟后心跳停止，3只20分钟后心跳停止。2．移植后NHBD-30组与HBD组相比，肺吸气末压、肺顺应性、LPD液灌注时间、PaO2、PaCO2、能量代谢、肺组织MPO和MDA含量、肺干／湿重比、超微结构的改变等指标的差别均无显著意义(P＞0.05)。3．移植后NHBD-60组与HBD组和NHBD-30组相比，上述指标的差别都有显著意义(P＜0.05)。
结论：热缺血30分钟的无心跳供体肺可以用于大白鼠的肺移植，其结构和功能均未发生显著的改变，热缺血60分钟的无心跳供体肺因结构破坏严重，功能基本丧失，不适于大白鼠的肺移植。
Background: A shortage of lung donors pool is a serious obstacle to the widespread application of lung transplantation for end-stage lung disease. The desire of enlarging the donors pool compels us to explore the feasibility of non-heart-beating donor in rat lung transplantaion.
Methods: Sixty Sprague-Dawley rats were randomly divided into 3 groups that lung of the rat were harvested immediately, 30 minutes and 60 minutes after cardiac-arrest. All the donor heparinized lungs were ventilated at the moment when they were flushed with the low potassium dextran solution and then stored in the same solution at 4 for 4 hours. The recipient animal underwent left thoracotomy, and then orthotopic left lung transplatation. The right pulmonary hilum were ligated 1 hour after reperfusion.
Results: All the recipients of heart-beating lungs and 30 minutes cadaver lungs survived the observation period with excellent gas exchange, whereas 4 of 10 recipients of 60 minutes cadaver lungs survived for 10 minutes after the ligation of right pulmonary hilum and 3 for 20 minutes. The microstructure, pulmonary compliance, energy metabolism and other markers show no significant difference between HBD group and NHBD-30 group.
Conclusion: The adoption non-heart-beating donor can be a safe and effective method to increase the lung donor pool. Since the ischemia-reperfusion injury shows more serious with the longer warm ischemic time, there should be a definition for the warm ischemia time, such as 30 minutes for the rat.
方法：取30对健康Sprague-Dawley大白鼠，即供体和受体，分成3组，即有心跳供体(HBD)组、无心跳供体—热缺血30分钟(NHBD-30)组、无心跳供体—热缺血60分钟(NHBD-60)组。3组均给予气管切开，连接呼吸机辅助呼吸，吸气氧浓度50％。供体鼠处死的方法均为剪断腹主动脉放血，HBD组供体在处死的同时灌注4℃LPD液，NHBD-30组、NHBD组供体处死后维持辅助呼吸，分别放置室温中30分钟或60分钟，再灌注低钾右旋糖苷(LPD)液。供肺置于4℃LPD液中4小时，留取左肺。受体鼠切除左肺，行“原位左肺移植术”。术后维持辅助呼吸1小时，经右侧进胸，阻断右肺门，测定观测指标。
结果：1．阻断右肺门后，HBD组、NHBD-30组存活时间均超过30分钟，NHBD-60组有4只10分钟后心跳停止，3只20分钟后心跳停止。2．移植后NHBD-30组与HBD组相比，肺吸气末压、肺顺应性、LPD液灌注时间、PaO2、PaCO2、能量代谢、肺组织MPO和MDA含量、肺干／湿重比、超微结构的改变等指标的差别均无显著意义(P＞0.05)。3．移植后NHBD-60组与HBD组和NHBD-30组相比，上述指标的差别都有显著意义(P＜0.05)。
结论：热缺血30分钟的无心跳供体肺可以用于大白鼠的肺移植，其结构和功能均未发生显著的改变，热缺血60分钟的无心跳供体肺因结构破坏严重，功能基本丧失，不适于大白鼠的肺移植。
Background: A shortage of lung donors pool is a serious obstacle to the widespread application of lung transplantation for end-stage lung disease. The desire of enlarging the donors pool compels us to explore the feasibility of non-heart-beating donor in rat lung transplantaion.
Methods: Sixty Sprague-Dawley rats were randomly divided into 3 groups that lung of the rat were harvested immediately, 30 minutes and 60 minutes after cardiac-arrest. All the donor heparinized lungs were ventilated at the moment when they were flushed with the low potassium dextran solution and then stored in the same solution at 4 for 4 hours. The recipient animal underwent left thoracotomy, and then orthotopic left lung transplatation. The right pulmonary hilum were ligated 1 hour after reperfusion.
Results: All the recipients of heart-beating lungs and 30 minutes cadaver lungs survived the observation period with excellent gas exchange, whereas 4 of 10 recipients of 60 minutes cadaver lungs survived for 10 minutes after the ligation of right pulmonary hilum and 3 for 20 minutes. The microstructure, pulmonary compliance, energy metabolism and other markers show no significant difference between HBD group and NHBD-30 group.
Conclusion: The adoption non-heart-beating donor can be a safe and effective method to increase the lung donor pool. Since the ischemia-reperfusion injury shows more serious with the longer warm ischemic time, there should be a definition for the warm ischemia time, such as 30 minutes for the rat.
引文
1． Hardy JD, Webb WR, Dalton ML, Walker GR. Lung homotransplantation in man. Report of the initial case. JAMA 1963;186:1065-74．
2． Brigham KL. Mechanisms of lung injury. Clin Chest Med 1982;3:8．
3． Blades B, Beattie EJ Jr, Hill RP, Thistlethwaite R. Ischemia of the lung. Ann Surg 1952; 136:56-62．
4． Blades B, Pierpont HC, Samadi, Hill RP. The effect of experimental lung ischemia on pulmonary function. Surg Forum 1953;4:255-60．
5． Lechner JF, Stoner GD, Y oakum GH, et al. In vitro carcinogenesis studies with human tracheobronchial tissues and cells, In: Schiff LJ, ed. In vitro models of respiratory epithelium. Boca Raton, FL: CRC Press, 1986:143-59．
6． Egan TM, Lambert CJ, Reddick R, et al. A strategy to increase the donor pool: use of cadaver lungs for transplantation. Ann Thorac Surg. 1991;52:1113-21．
7． Jones DR, Bedker RM, Hoffmann SC, et al. When does the lung die? Kfc,cell fiability, and adenine nucleotide changes in the circulation-arrested rat lung. J Appl Physiol.1997 Jul;83(1) :247-52．
8． Homatas J, Bryant L, Eiseman B. Time limits of cadaver lung viability. J Thorac Cardiovasc Surg 1996;56:132-40．
9． Yamazaki F, Wada H, Aoki M, Inui K, Hitomi S. An evaluation of the tolerance of the autotransplanted canine lung against warm ischemia. Jpn J Surg 1989;19:326-33．
10． Van Raemdonck DE, Jannis NC, De Leyn PR, et al. Warm ischemic tolerance in collapsed pulmonary graftsis limited to 1 hour. Ann Surg 1998;228(6) :788-96．
11 . Greco R, Benito J, De Miguel E, et al. Lung transplantation from vantilated non-heart-beating donors experimental study in a neonatal swine model. J Pediatr Surg 1999;34(2) :360-366．
12． Greco R, Cordovilla G, Sanz E, et al. Warm ischemic time tolerance after ventilated non-heart-beating lung donation in piglets. Eur J Cardiothorac Surg 1998 Sep:14(3) :319-25．
13． Buchanan SA, DeLima NF, Binns OAR, et al. Pulmonary function after non-heart-beation lung donation in a survival model. Ann Thorac Surg 1995;60:38-46．
14． Boglione MM; Morandini MA; Barrenechea ME, et al. Pre-arrest heparinization and ventilation during warm ischemia preserves lung funcion in non-heart-beating donors. J Pediatr Surg 1999 Eec; 34(12) :1805-9．
15． Thomas D, Stein M,Tanabe G, et al. Mechanism of bronchoconstriction produced by thromboemboli in dog. Am J Physiol 1967;206:1207-12．
16． Takashima S, Date H, Aoe M, et al. Short-term inhaled nitrid oxide in canine lung transplantation from non-heart-beating donor. Ann Thorac Surg. 2000;70:1679-83．
17． Umemeori Y, Date H, Uno K, et al. Improved lung function by urokinase infusion in canine lung transplantation using non-heart-beating donors. Ann Thorac Surg 1995;59:1513-8．
18． Date H, Matsumura A, Manchester JK, et al.Changes in alveolar oxygen and carbon dioxide concentration and oxygen consumption during lung preservation. J Thorac Cardiovasc Surg. 1993 Mar;105(3) :492-501．
19． Watanabe A, Kawaharada N, Kusajima K, et al. Influence of oxygen in inflation gas during lung ischemia on ischemia-reperfusion injury. J Thorac Cardiovasc Surg. 1997 Sep;114(3) :332-8．
20． Van Raemdonck DE, Jannis ND, Rdga FR, et al. Delay of adenosine triphosphate depletuon and hypoxanthine formation in rabbit lung after death. Ann Thorac Surg 1996 Jul;62(l):233-40．
21 . D'Armini AM, Tom EJ, Roberts CS, et al. When does the lung die?Time course of high energy phosphate depletion and relationship to lung viability after "death". J Surg Res. 1995 Oct;59(4) :468-74．
22． D'Armini AM, Roberts CS, Griffith PK, et al. When does the lung die? I .Histochemical evidence of pulmonary viability after "death". J Heart Lung Transplant 1994 Sep-Oct;13(5) :741-7．
23 . Alessandtini F, D'Armini AM, Roberts CS, et al. When does the lung die? II .Ultrastructural evidence of pulmonary viability after "death". J Heart Lung Transplant 1994 Sep-Oct;13(5) :748-57．
24． Ulicny KS, Egan TM, Lambert CJ, et al. Cadaver lung donors:Effect of preharvest ventilationon graft function. Ann Thorac Surg 1993;55:1185-1191．
25． Haniuda M, Hasegawa S, Shiraishi T, et al. The maintenance of aerobic metabolism during lung preservation. Effects of inflation volume during lung preservation on pulmonary capillary permeability. J Thorac Cardiovasc Surg. 1996 Jul;l 12(l):85-93．
26． The Toronto Lung Transplant Group: Unilateral lung transplantation for pulmonary fibrosis. N Engl J Med 1986;314:1140-5．
27． Steen S, Ingemansson R, Budrikis A, et al. Successful transplantation of lungs topically cooled in the non-heart-beating donor for 6 hours. Ann Thorac Surg 1997;63:345-51．
28． Van Raemdonck DE, Jannis NC, Rega FR, et al. External cooling of warm ischemic rabbit lungs after death. Ann Thorac Surg 1996 Aug;62(2) :331-7．
29． Belzer FO, Southard JH. Principles of solid-organ preservation by cold storage. Transplantation 1988;50:573．
30． Collins GM. Flush preservation. In: Pegg DE, Jacobsen IA, Halasz NA, eds. Organ preservaton: basic and applied aspects. Lancaster, England: MTP Press, 1982:167．
31 . Marshall JM. Vertebrate and smooth muslce. In: Mountcastle VB, ed. Medical physiology. Vol 1． 14th ed. St. Louis: Mosby, 1980:120．
32． Yamazaki R, Yokomise H, Keshavjee SH, et al. The superiority of an extracellular fluid solution over Euro-Collins solution for pulmonary preservation. Transplantation 1990;49:690-4．
33． Keshavjee. SH, Yamazaki. MSc, Yokomise. H, et al. The role of dextran 40 and potassium in extended hypothermic lung preservation for transplantation. J Thorac Cardiovasc Surg 1992;103:314-25．
34． Pegg DE. Organ preservation. Surg Clin North Am 1986;66:617．
35． King RC, Binns OA, Kanithanon RC, et al. Acellular low-potassium dextran preserves pulmonary function after 48 hours of ischemia. Ann Thorac Surg 1997 Sep;64(3) :795-800．
36． Miyoshi S, Shimokawa S, Schreinemakers H, et al. Comparison of the University of Wisconsin preservation solution and other crystalloid perfusates in a 30-hour rabbit lung preservation model. J Thorac Cardiovasc Surg 1992 Jan;103(1) :27-32．
37． Novick RJ, Gehman KE, Ali IS, et al. Lung preservation: the importance of endothelial and alveolar type II cell integrity. Ann Thorac Surg 1996;62:302-14．
38． Lefer AM, Lefer DJ. Pharmacology of the endothelium in ischemia-reperfusion and circulatory shock. Annu Rev Pharmacol Toxicol 1993;259:L315-9．
39． Tsao PS, Lefer AM. Time course and mechanism of endothelial dysfunction in isolated
ischeic and hypoxic perfused rat heart. Am J Physiol 1990;259: 1660-6．
40． Breda MA, Hall TS, Stuart S, et al. Twenty-four hour lung perservation by hypothermia and leucocyte depletion. J Heart Transplant 1985;4:325-9．
41． Gee MH, Albertine KH. Neutrophil-endothelial cell interactions in the lung. Annu Rev Physiol 1993;55:227-48．
42． Ward PA, Till GO, Warren JS. Pathophysiology of leukocyte-mediated tissue injury. J Crit Care 1991;6:1 12-6．
43． Gee MH, Albertine KH. Neutrophil-endothelial cell inter actions in the lung. Annu Tev Physiol 1993;55 :227-48．
44． Eppinger MJ, Jones ML, Deeb BM, Boiling SG, Ward PA. Pattern of injury and role of neutrophils in reperfusion injury of rat lung. J Surg Res 1995;58:713-8．
45． Xing Z, Kirpalani H, Tony D, Jordana M, Gauldie J. Polymofphonuclear leukocytes as a significant source of tumor necrosis factor-a in endotoxin-challenged lung tissue. Am J Pathol 1993:143:1009-15．
46． Williams JH, Patel SK, Hatakeyama D, et al. Activated pulmonary vascular neutrophils as early mediators of endotoxm-induced lung inflammation. Am J Respir Cell Mol Biol 1993;8:134-44．
47． Stricter RM, Kasahara K, Allen RM, et al. Cytokine-induced neutrophil-derived interleukm-8． Am J Pathol 1992;141:397-407．
48． Brain SD, Williams TJ. Leukotrienes and inflammation. Pharmacol Ther 1990;46:57-66．
49． Lefer AM, Lefer DJ. Pharamacology of the endothelium in ischemia-reperfusion and circulatory shock. Annu Rev Pharmacol Toxicol 1993;33:71-90．
50． Baird BR, Cheronis JC, Sandhaus RA, Berger EM, White CW, Repine JE. O2 metabolites and neutrophil elastase synergistically cause edematous injury in isolated rat lungs. J Appl Physiol 1986;61:2224-9．
51． Kinkade JM, Pember SO, Barnes KC, et al. Differential distribution of distinct forms of myeloperoxidase in different azurophilic granule subpopulations from human neutrophils. Biochem Biophys Res Commun. 1983; 114:296-303．
52． Schultz J, Kaminker K. Myeloperoxidase of the leucocyte of normal human blood. I.Content and localization. Arch Biochem Biophys. 1962;96:465-7．
53． Goldblum SE, Wu KM, Jay M. et al. Lung mydloperoxidase as a measure of pulmonary leukostasis in rabbits. J Appl Physiol. 1985 Dec;59(6) : 1978-85．
54． 赵克然,杨毅军,曹道骏.氧自由基与临床.中国医药科技出版社. 1999．
55． McCord JM McCord JM. Oxygen-derived free radicals in post ischemic tissue unjury. N EnglJMed 1985;312:158．
56． Murakami S, Bacha EA, Herve P, et al. Inhaled nitric oxide and pentoxifylline in rat lung transplantation from non-heart-beating donors. J Thorac Cardio Surg 1997;113(5) :821-9．
57． Van Raemdonck DEM, Jannis NCP, Rega FRL, et al. Extended preservation of ischemic pulmonary graft by postmortem alveolar expansion. Ann Thorac Surg 1997;64:810-8．
2． Brigham KL. Mechanisms of lung injury. Clin Chest Med 1982;3:8．
3． Blades B, Beattie EJ Jr, Hill RP, Thistlethwaite R. Ischemia of the lung. Ann Surg 1952; 136:56-62．
4． Blades B, Pierpont HC, Samadi, Hill RP. The effect of experimental lung ischemia on pulmonary function. Surg Forum 1953;4:255-60．
5． Lechner JF, Stoner GD, Y oakum GH, et al. In vitro carcinogenesis studies with human tracheobronchial tissues and cells, In: Schiff LJ, ed. In vitro models of respiratory epithelium. Boca Raton, FL: CRC Press, 1986:143-59．
6． Egan TM, Lambert CJ, Reddick R, et al. A strategy to increase the donor pool: use of cadaver lungs for transplantation. Ann Thorac Surg. 1991;52:1113-21．
7． Jones DR, Bedker RM, Hoffmann SC, et al. When does the lung die? Kfc,cell fiability, and adenine nucleotide changes in the circulation-arrested rat lung. J Appl Physiol.1997 Jul;83(1) :247-52．
8． Homatas J, Bryant L, Eiseman B. Time limits of cadaver lung viability. J Thorac Cardiovasc Surg 1996;56:132-40．
9． Yamazaki F, Wada H, Aoki M, Inui K, Hitomi S. An evaluation of the tolerance of the autotransplanted canine lung against warm ischemia. Jpn J Surg 1989;19:326-33．
10． Van Raemdonck DE, Jannis NC, De Leyn PR, et al. Warm ischemic tolerance in collapsed pulmonary graftsis limited to 1 hour. Ann Surg 1998;228(6) :788-96．
11 . Greco R, Benito J, De Miguel E, et al. Lung transplantation from vantilated non-heart-beating donors experimental study in a neonatal swine model. J Pediatr Surg 1999;34(2) :360-366．
12． Greco R, Cordovilla G, Sanz E, et al. Warm ischemic time tolerance after ventilated non-heart-beating lung donation in piglets. Eur J Cardiothorac Surg 1998 Sep:14(3) :319-25．
13． Buchanan SA, DeLima NF, Binns OAR, et al. Pulmonary function after non-heart-beation lung donation in a survival model. Ann Thorac Surg 1995;60:38-46．
14． Boglione MM; Morandini MA; Barrenechea ME, et al. Pre-arrest heparinization and ventilation during warm ischemia preserves lung funcion in non-heart-beating donors. J Pediatr Surg 1999 Eec; 34(12) :1805-9．
15． Thomas D, Stein M,Tanabe G, et al. Mechanism of bronchoconstriction produced by thromboemboli in dog. Am J Physiol 1967;206:1207-12．
16． Takashima S, Date H, Aoe M, et al. Short-term inhaled nitrid oxide in canine lung transplantation from non-heart-beating donor. Ann Thorac Surg. 2000;70:1679-83．
17． Umemeori Y, Date H, Uno K, et al. Improved lung function by urokinase infusion in canine lung transplantation using non-heart-beating donors. Ann Thorac Surg 1995;59:1513-8．
18． Date H, Matsumura A, Manchester JK, et al.Changes in alveolar oxygen and carbon dioxide concentration and oxygen consumption during lung preservation. J Thorac Cardiovasc Surg. 1993 Mar;105(3) :492-501．
19． Watanabe A, Kawaharada N, Kusajima K, et al. Influence of oxygen in inflation gas during lung ischemia on ischemia-reperfusion injury. J Thorac Cardiovasc Surg. 1997 Sep;114(3) :332-8．
20． Van Raemdonck DE, Jannis ND, Rdga FR, et al. Delay of adenosine triphosphate depletuon and hypoxanthine formation in rabbit lung after death. Ann Thorac Surg 1996 Jul;62(l):233-40．
21 . D'Armini AM, Tom EJ, Roberts CS, et al. When does the lung die?Time course of high energy phosphate depletion and relationship to lung viability after "death". J Surg Res. 1995 Oct;59(4) :468-74．
22． D'Armini AM, Roberts CS, Griffith PK, et al. When does the lung die? I .Histochemical evidence of pulmonary viability after "death". J Heart Lung Transplant 1994 Sep-Oct;13(5) :741-7．
23 . Alessandtini F, D'Armini AM, Roberts CS, et al. When does the lung die? II .Ultrastructural evidence of pulmonary viability after "death". J Heart Lung Transplant 1994 Sep-Oct;13(5) :748-57．
24． Ulicny KS, Egan TM, Lambert CJ, et al. Cadaver lung donors:Effect of preharvest ventilationon graft function. Ann Thorac Surg 1993;55:1185-1191．
25． Haniuda M, Hasegawa S, Shiraishi T, et al. The maintenance of aerobic metabolism during lung preservation. Effects of inflation volume during lung preservation on pulmonary capillary permeability. J Thorac Cardiovasc Surg. 1996 Jul;l 12(l):85-93．
26． The Toronto Lung Transplant Group: Unilateral lung transplantation for pulmonary fibrosis. N Engl J Med 1986;314:1140-5．
27． Steen S, Ingemansson R, Budrikis A, et al. Successful transplantation of lungs topically cooled in the non-heart-beating donor for 6 hours. Ann Thorac Surg 1997;63:345-51．
28． Van Raemdonck DE, Jannis NC, Rega FR, et al. External cooling of warm ischemic rabbit lungs after death. Ann Thorac Surg 1996 Aug;62(2) :331-7．
29． Belzer FO, Southard JH. Principles of solid-organ preservation by cold storage. Transplantation 1988;50:573．
30． Collins GM. Flush preservation. In: Pegg DE, Jacobsen IA, Halasz NA, eds. Organ preservaton: basic and applied aspects. Lancaster, England: MTP Press, 1982:167．
31 . Marshall JM. Vertebrate and smooth muslce. In: Mountcastle VB, ed. Medical physiology. Vol 1． 14th ed. St. Louis: Mosby, 1980:120．
32． Yamazaki R, Yokomise H, Keshavjee SH, et al. The superiority of an extracellular fluid solution over Euro-Collins solution for pulmonary preservation. Transplantation 1990;49:690-4．
33． Keshavjee. SH, Yamazaki. MSc, Yokomise. H, et al. The role of dextran 40 and potassium in extended hypothermic lung preservation for transplantation. J Thorac Cardiovasc Surg 1992;103:314-25．
34． Pegg DE. Organ preservation. Surg Clin North Am 1986;66:617．
35． King RC, Binns OA, Kanithanon RC, et al. Acellular low-potassium dextran preserves pulmonary function after 48 hours of ischemia. Ann Thorac Surg 1997 Sep;64(3) :795-800．
36． Miyoshi S, Shimokawa S, Schreinemakers H, et al. Comparison of the University of Wisconsin preservation solution and other crystalloid perfusates in a 30-hour rabbit lung preservation model. J Thorac Cardiovasc Surg 1992 Jan;103(1) :27-32．
37． Novick RJ, Gehman KE, Ali IS, et al. Lung preservation: the importance of endothelial and alveolar type II cell integrity. Ann Thorac Surg 1996;62:302-14．
38． Lefer AM, Lefer DJ. Pharmacology of the endothelium in ischemia-reperfusion and circulatory shock. Annu Rev Pharmacol Toxicol 1993;259:L315-9．
39． Tsao PS, Lefer AM. Time course and mechanism of endothelial dysfunction in isolated
ischeic and hypoxic perfused rat heart. Am J Physiol 1990;259: 1660-6．
40． Breda MA, Hall TS, Stuart S, et al. Twenty-four hour lung perservation by hypothermia and leucocyte depletion. J Heart Transplant 1985;4:325-9．
41． Gee MH, Albertine KH. Neutrophil-endothelial cell interactions in the lung. Annu Rev Physiol 1993;55:227-48．
42． Ward PA, Till GO, Warren JS. Pathophysiology of leukocyte-mediated tissue injury. J Crit Care 1991;6:1 12-6．
43． Gee MH, Albertine KH. Neutrophil-endothelial cell inter actions in the lung. Annu Tev Physiol 1993;55 :227-48．
44． Eppinger MJ, Jones ML, Deeb BM, Boiling SG, Ward PA. Pattern of injury and role of neutrophils in reperfusion injury of rat lung. J Surg Res 1995;58:713-8．
45． Xing Z, Kirpalani H, Tony D, Jordana M, Gauldie J. Polymofphonuclear leukocytes as a significant source of tumor necrosis factor-a in endotoxin-challenged lung tissue. Am J Pathol 1993:143:1009-15．
46． Williams JH, Patel SK, Hatakeyama D, et al. Activated pulmonary vascular neutrophils as early mediators of endotoxm-induced lung inflammation. Am J Respir Cell Mol Biol 1993;8:134-44．
47． Stricter RM, Kasahara K, Allen RM, et al. Cytokine-induced neutrophil-derived interleukm-8． Am J Pathol 1992;141:397-407．
48． Brain SD, Williams TJ. Leukotrienes and inflammation. Pharmacol Ther 1990;46:57-66．
49． Lefer AM, Lefer DJ. Pharamacology of the endothelium in ischemia-reperfusion and circulatory shock. Annu Rev Pharmacol Toxicol 1993;33:71-90．
50． Baird BR, Cheronis JC, Sandhaus RA, Berger EM, White CW, Repine JE. O2 metabolites and neutrophil elastase synergistically cause edematous injury in isolated rat lungs. J Appl Physiol 1986;61:2224-9．
51． Kinkade JM, Pember SO, Barnes KC, et al. Differential distribution of distinct forms of myeloperoxidase in different azurophilic granule subpopulations from human neutrophils. Biochem Biophys Res Commun. 1983; 114:296-303．
52． Schultz J, Kaminker K. Myeloperoxidase of the leucocyte of normal human blood. I.Content and localization. Arch Biochem Biophys. 1962;96:465-7．
53． Goldblum SE, Wu KM, Jay M. et al. Lung mydloperoxidase as a measure of pulmonary leukostasis in rabbits. J Appl Physiol. 1985 Dec;59(6) : 1978-85．
54． 赵克然,杨毅军,曹道骏.氧自由基与临床.中国医药科技出版社. 1999．
55． McCord JM McCord JM. Oxygen-derived free radicals in post ischemic tissue unjury. N EnglJMed 1985;312:158．
56． Murakami S, Bacha EA, Herve P, et al. Inhaled nitric oxide and pentoxifylline in rat lung transplantation from non-heart-beating donors. J Thorac Cardio Surg 1997;113(5) :821-9．
57． Van Raemdonck DEM, Jannis NCP, Rega FRL, et al. Extended preservation of ischemic pulmonary graft by postmortem alveolar expansion. Ann Thorac Surg 1997;64:810-8．