肝素治疗浅Ⅱ度烧伤的临床观察
摘要
目的：烧伤后细胞和组织损伤由热力引起，随局部缺血而加重。炎症介质激活可启动级联反应(cascades)使细胞进一步受损。严重烧伤往往出现内脏并发症、感染、MOF等，创面愈合缓慢、疤痕增生和挛缩。GAGs是一组酸性、带负电荷、由一个羟基和一个或多个硫酸根的二糖重复组成的长链化合物，结构和功能类似多聚糖。内源性GAGs包括肝素、硫酸乙酰肝素、硫酸角质素、硫酸皮肤素、硫酸软骨素4和6、透明质酸等。研究发现，GAGs治疗烧伤有多种作用。本研究通过对临床病人应用肝素后的观察，探讨肝素对浅Ⅱ度烧伤的治疗效果。
方法：临床选择以浅Ⅱ度创面为主病人80例，男58例，女22例，年龄1-55岁，烧伤总面积3％-50％TBSA，随机分治疗组4 0例，对照组40例，两组病人均为伤后24h内收入病房新鲜创面，采用异体同部位对照，两组患者的年龄及全身一般状况相差不大。两组患者创面均行简单清创，治疗组肝素直接均匀喷洒于创面，或注入疱皮内，凡士林油纱浸湿5g／L碘伏内衬于创面，外加3-5 cm无菌干纱布包扎，每天换药1次。对照组单纯碘伏油纱内衬无菌干纱布包扎。两组患者视全身情况和烧伤面积给予同样的全身治疗。比较两组患者用药后疼痛缓解的时间，创面表现，计算创面愈合的天数(愈合标准残余创面<1％)，监测凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、血小板(PLT)变化，以及全身及创面有无出血现象。
结果：治疗组止痛起效快，持续时间长，创面水肿消退早，渗血早，感染轻，愈合时间短。
结论：肝素直接用于浅Ⅱ度创面，能迅速止痛、肝素的作用包括抑制炎症、缓解疼痛、保护细胞、促进血管生成、促进上皮生长并改善愈合皮肤质量。
Objective: Bums are difficult to treat, wounds with complex local and systemic pathology and high mortality, that often heal slowly with scars and contractures. Glycosaminoglycans (GAGs) have been used in parenteral and topical application studies. These studies have uncovered anticoagulative, antiinflammatory and neoangiogenic properties, which may stimulate tissue repair and reepithelializing effects. The endogenous GAGs utilized in treating burns are heparin, dermatan sulfate, heparin sulfate, keratin sulfate, chondroitin-4- and chondroitin-6-sulfate, and hyaluronic acid. Heparin, the most sulfated and acidic GAG, has been used to investigate the effects of heparin on the superficial second-degree burn wounds.
Methods: Eighty patients with 3-50% TBSA superficial second-degree burn wounds were devided into two groups, the heparin-treatment group and the control group.Heparin was used in 40 cases of patients, the other 40 cases in the control group were treated with routine methods. Patients were as same as each other on age and normal situations. Heparin was used on the wound or injected into blisters in the heparin-treatment group ,but not used in the control group. The patient's pain level was assessed using a visual analog scale (VAS) before and after the treatment. Wound aspect ,platelet number,and wound healing time were observed .Heparin therapy is commonly monitored by the activated partial thromboplastin time (APTT) .To see if there were bleeding.
All data were analyzed with statistics.
Results: The wound healing time was much shorter in the treatment group than that in the control group : 8.4±2.0 days vs. 13.8±1.0 days; P<0.05; In the treatment group, the burn wounds were clean and the reaction of inflammation was slight. Heparin could promote healing of the burn wounds, indicating significant difference in two groups . The difference in PT and APTT between the two groups was not significant (P>0.05).
Conclusion: Heparin relieved pain, inhibited clotting and inflammation, restored blood flow, and enhanced healing, The healed skin was smooth, Collagen restoration was enhanced. Heparin reduced needs for pain medicine, topical antibiotics, resuscitation fluids, blood, water baths, debridement, surgery and grafts. Cost of treatments were reduced. Although not as yet fully substantiated, topical heparin therapy of burns may be a useful addition to the range of available treatments for burn wounds.
方法：临床选择以浅Ⅱ度创面为主病人80例，男58例，女22例，年龄1-55岁，烧伤总面积3％-50％TBSA，随机分治疗组4 0例，对照组40例，两组病人均为伤后24h内收入病房新鲜创面，采用异体同部位对照，两组患者的年龄及全身一般状况相差不大。两组患者创面均行简单清创，治疗组肝素直接均匀喷洒于创面，或注入疱皮内，凡士林油纱浸湿5g／L碘伏内衬于创面，外加3-5 cm无菌干纱布包扎，每天换药1次。对照组单纯碘伏油纱内衬无菌干纱布包扎。两组患者视全身情况和烧伤面积给予同样的全身治疗。比较两组患者用药后疼痛缓解的时间，创面表现，计算创面愈合的天数(愈合标准残余创面<1％)，监测凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、血小板(PLT)变化，以及全身及创面有无出血现象。
结果：治疗组止痛起效快，持续时间长，创面水肿消退早，渗血早，感染轻，愈合时间短。
结论：肝素直接用于浅Ⅱ度创面，能迅速止痛、肝素的作用包括抑制炎症、缓解疼痛、保护细胞、促进血管生成、促进上皮生长并改善愈合皮肤质量。
Objective: Bums are difficult to treat, wounds with complex local and systemic pathology and high mortality, that often heal slowly with scars and contractures. Glycosaminoglycans (GAGs) have been used in parenteral and topical application studies. These studies have uncovered anticoagulative, antiinflammatory and neoangiogenic properties, which may stimulate tissue repair and reepithelializing effects. The endogenous GAGs utilized in treating burns are heparin, dermatan sulfate, heparin sulfate, keratin sulfate, chondroitin-4- and chondroitin-6-sulfate, and hyaluronic acid. Heparin, the most sulfated and acidic GAG, has been used to investigate the effects of heparin on the superficial second-degree burn wounds.
Methods: Eighty patients with 3-50% TBSA superficial second-degree burn wounds were devided into two groups, the heparin-treatment group and the control group.Heparin was used in 40 cases of patients, the other 40 cases in the control group were treated with routine methods. Patients were as same as each other on age and normal situations. Heparin was used on the wound or injected into blisters in the heparin-treatment group ,but not used in the control group. The patient's pain level was assessed using a visual analog scale (VAS) before and after the treatment. Wound aspect ,platelet number,and wound healing time were observed .Heparin therapy is commonly monitored by the activated partial thromboplastin time (APTT) .To see if there were bleeding.
All data were analyzed with statistics.
Results: The wound healing time was much shorter in the treatment group than that in the control group : 8.4±2.0 days vs. 13.8±1.0 days; P<0.05; In the treatment group, the burn wounds were clean and the reaction of inflammation was slight. Heparin could promote healing of the burn wounds, indicating significant difference in two groups . The difference in PT and APTT between the two groups was not significant (P>0.05).
Conclusion: Heparin relieved pain, inhibited clotting and inflammation, restored blood flow, and enhanced healing, The healed skin was smooth, Collagen restoration was enhanced. Heparin reduced needs for pain medicine, topical antibiotics, resuscitation fluids, blood, water baths, debridement, surgery and grafts. Cost of treatments were reduced. Although not as yet fully substantiated, topical heparin therapy of burns may be a useful addition to the range of available treatments for burn wounds.
引文
1． 李巧玲．肝素治疗烧伤的研究和应用回顾．医学研究生学 报．2003，16(4)：300-302．
2．杭守云．LMWH对烧伤创面微循环影响的实验研究．皖南医学院学 报，2001，20：03．
3. Saliba Mj Jr ,Dempsey WC ,Kruggel JL.Large bums in humans ,treat2 ment with heparin[J ].J Am Med Assoc ,1973 ,225 :261.
4．陈玉林，黄康．创面愈合的评价指标．中国临床康复．2002，6(8)：1080-1081．
5．杨藻宸，主编．医用药理学．第3版．北京：人民卫生出版社，1997．518-520．
6．华云飞．肝素在烧伤治疗中的应用．中华实用医学．2004，6(6)：612．
7. Saliba MJ Jr. Heparin ,natre' s own burn remedy ? [J ] Emerg Med , 1973,106:111.
8. Macaig T ,luehlman T ,Friesel R , et al. Heparin binds endothelial cell growth factor ,the principal endothelial cell mitogen in bovine brain [J ]. Science, 1984 ,225:932.
9. Folkman J ,Shing Y. Control of angiogenesis by heparin and other sul2 fated polysaccharides[J ]. Adv Exp Med Biol ,1992 ,313 :3552364.
10. Azizkhan RG,Azizkhan JC ,Zetter BR , et al. Mast cell heparin stimu2 lates migration of capillary endothelial cells in vitro [J ]. J Exp Med , 1980,152:931.
11. Zapata2Sirvant RL ,Hansbrough JF , Greedleaf GE , et al. Reduction of bacterial translocation and intestinal structure alterations by heparin in a murine burn??injury model[J ].J Trauma ,1994 ,36 :126.
12. Gianotti L ,Alezander JW ,Fukushima R, et al. Reduction of bacteriatranslocation with oral fibroblast growth factor and sucrafate[J ]. Am J Surg, 1993 ,165:1952200.
13. Saliba MJ Jr. The effects and used of heparin in the care of burns thatimproves treatment and enhances the quality of life [J ]. Acta Chirur Plast,1997 ,39:13216.
14. Saliba MJ Jr ,Friner LA. Heparin efficac in burns. I . Significant early modification of experimental third2degree guines pig thermal burn[J ]. Aerosp Med,1970,41 :179.
15. Carr J . The anti2inflammatory action of heparin :heparin as an antago2 nistto histamine ,bradykinin ,and prostaglandin E1[J ]. Thromb Res , 1979,16:5072516.
16. Shanberge JN ,Kambayashi J ,Nakagawa M. The interaction of platelets with a tritium21abeled heparin[J]. Thromb Res ,1976,23 .-2642271.
17. Rent R ,Nyirman RRR ,Fiedel BA, et al. Potenitiation of Cl esteraseinhibitor activity by heparin [J ]. Clin Exp Immunol, 1976 ,23 : 2642 271.
18. Hiebert LM ,Lui JM. Heparin protects cultured arterial endothelial cells from damage by toxic oxygen metabolities[J ]. Arteriosclerosis ,1990 , 83 :37251.
19．张红兵．肝素在婴幼儿深度烧伤治疗中的作用．华北煤碳医学院学 报．2005，7(3)：288-289．
20. Lider O ,Bahav E ,Mekori YA , et al. Suppression of experimental auto2 immune diseases and prolongation of allograft survival by treating ani2 mals with??low doses of heparin[J ].J Clin Invest ,1989 ,83 :7522766.
21. Wright J G,Massop DW ,Rurst J G, et al. Pre2ischemic heparinizationdecreases rat skeletal muscke reperfusion injury [ J ]. J Cardiovasc Surg ,1991 ,32(sp): II. Abstract.
22. Sternberg WCⅢ,Makhoul RG,Adelman B. Heparin prevents postisch2 emic endothelial cell dysfunction by a mechanism independent of its an2 ticoagulant activity[J ].J Vasc Surg ,1993 ,17 :3182327.
23．罗攀，岑瑛，赵景华．肝素对Ⅱ度烧伤大鼠免疫功能的影响[J]．华西医 学，2000，15(1)：32233．
24．严小蓉，罗攀，岑瑛．肝素对深Ⅱ度烧伤大鼠的影响[J]．中华烧伤杂 志，2001，17(3)：1742176．
25. Ramakrishanan KM ,Babu M ,Tamachandran K. Effects of heparin oncollagen in burns[C]. Int Trans of the Plastic and Reconstructive Sur2 gery Congress. Montreal ,Canada ,1984.
1. Glucosanminoglycans. In :Burns :Multi2Center Update [ C]. Proc 10th Congr of International Society for Burn Injuries.Jerusalem. Israel ,125 November ,1998. Abstracts.
2 Saliba MJ Jr ,edit. The Effects of Heparin in the Treatment of Burn[C]. Int Meet ,24227. 1994 ,San Diego ,CA.
3 Elrod PD ,McCIeary RS ,Ball OT. An experimental study of the effect of heparin on survival time following lethal bruns[J ]. Surg Gyn Ob2 stet, 1951,92:35242.
4 Green BE ,Artz CP. An appraisal of heparin in burns : experimental study[J ]. Surg Forum ,1959 ,10 :343.
5 Saliba MJ Jr. Heparin in the treatment of burns[J ].J Am Med Assoc , 1967,200:650.
6 Saliba MJ Jr. Heparin efficacy in burns. II . Human thermal burn treatment which large doses of tipcal and parenteral heparin[J ]. Aero2 sp Med, 1970 ,41 :1302.
7 Saliba Mj Jr ,Dempsey WC ,Kruggel JL.Large burns in humans ,treat2 ment with heparin[J ].J Am Med Assoc ,1973 ,225 :261.
8 Saliba MJ Jr. Heparin ,natre' s own burn remedy ? [J ] Emerg Med , 1973,106:111.
9 杭守云．LMWH对烧伤创面微循环影响的实验研究[J]．皖南医学院学报，2001，20：03．
10 Macaig T ,luehlman T ,Friesel R , et al. Heparin binds endothelial cell growth factor ,the principal endothelial cell mitogen in bovine brain [J]. Science,1984,225:932.
11 Folkman J ,Shing Y. Control of angiogenesis by heparin and other sul2 fated polysaccharides[J]. Adv Exp Med Biol ,1992 ,313 :3552364.
12 Azizkhan RG,Azizkhan JC ,Zetter BR , et al. Mast cell heparin stimu2 lates migration of capillary endothelial cells in vitro[J]. J Exp Med , 1980 ,152 :931.
13 Zapata2Sirvant RL ,Hansbrough JF , Greedleaf GE , et al. Reduction of bacterial translocation and intestinal structure alterations by heparin in a murine burn injury model[J].J Trauma ,1994 ,36 :126.
14 Gianotti L ,Alezander JW ,Fukushima R , et al. Reduction of bacteria translocation with oral fibroblast growth factor and sucrafate[J]. Am J Surg, 1993 ,165:1952200.
15 Saliba MJ Jr. The effects and used of heparin in the care of burns that improves treatment and enhances the quality of life [J]. Acta Chirur Plast,1997 ,39:13216.
16 Saliba MJ Jr ,Friner LA. Heparin efficac in burns. I . Significant early modification of experimental third2degree guines pig thermal burn[J]. Aerosp Med,1970 ,41 :179.
17 Carr J . The anti2inflammatory action of heparin :heparin as an antago2 nist to histamine ,bradykinin ,and prostaglandin E1[J]. Thromb Res , 1979 ,16 :5072516.
18 Shanberge JN ,Kambayashi J ,Nakagawa M. The interaction of platelets with a tritium21abeled heparin[J ]. Thromb Res ,1976 ,23 :2642271.
19 Rent R ,Nyirman RRR ,Fiedel BA , et al. Potenitiation of Cl esterase inhibitor activity by heparin [J ]. Clin Exp Immunol ,1976 ,23 : 2642 271.
20 Hiebert LM ,Lui JM. Heparin protects cultured arterial endothelial cells from damage by toxic oxygen metabolities[J ]. Arteriosclerosis ,1990 , 83 :37251.
21 Lantz M ,Thysell H ,Nilsson E , et al. On the binding of tumor2nectosis2 factor( TNF) to heparin and the release in vivo of the TNF2binding protein I by heparin[J ].J Clin Invest ,1991 ,88 :202622031.
22 Lider O ,Bahav E ,Mekori YA , et al. Suppression of experimental auto2 immune diseases and prolongation of allograft survival by treating ani2 mals with low doses of heparin[J ].J Clin Invest ,1989 ,83 :7522766.
23 Wright J G,Massop DW ,Rurst J G, et al. Pre2ischemic heparinization decreases rat skeletal muscke reperfusion injury [J]. J Cardiovasc Surg ,1991 ,32(sp): Ⅱ. Abstract.
24 Sternberg WC Ⅲ,Makhoul RG,Adelman B. Heparin prevents postisch2 emic endothelial cell dysfunction by a mechanism independent of its an2 ticoagulant activity[J ].J Vasc Surg ,1993 ,17 :3182327.
25 罗攀，岑瑛，赵景华．肝素对Ⅱ度烧伤大鼠免疫功能的影 响[J]．华西医学，2000，15(1)：32233．
26 严小蓉，罗攀，岑瑛．肝素对深Ⅱ度烧伤大鼠的影响[J]．中华烧伤杂志，2001，17(3)：1742176．
27 Ramakrishanan KM ,Babu M ,Tamachandran K. Effects of heparin on collagen in burns[C]. Int Trans of the Plastic and Reconstructive Sur2 gery Congress. Montreal ,Canada ,1984.
28 Ferrao AV ,Mason RM. The effect of heparin on cell proliferation and type2 I collagen synthesis by adult human dermal fibroblasts[J ]. Bio2 chem Biophys Acta, 1993 ,1180 :2252230.
29 张远贵，许伟石，史济湘．类肝素对大鼠深Ⅱ度烫伤创面愈合的影响[J]．中华整形外科杂志，1998，02：1002103．
30 Cox CS ,Zwischenberger JB ,Traber DL , et al. Heparin improves oxy2 genation and minimizes barotrauma after severe smoke inhalation in ovine model[J ]. Surg Gynecol Obstet ,1993 ,76 :3392349.
31 Desai MH MD ,Micak RT ,Richardson RCP , et al. Reduction in mor2 tality in pediatric pationts with inhalation injury with aerosolized hepa2 rin N2acetylcysteine therapy[J ]. J Burn Care Rehabil ,1998 ,19 (3): 2102213.
32 RockwellWB,Eh rlich HP. Fibrinolysis inhibition in human burn blister fluid. J Burn Care Rehabil, 1990,11:126.
33 张文安，岑瑛，李文，等．肝素对Ⅱ度烫伤在鼠细菌移位影响的实验研究[J]．中华烧伤杂志，2002，18(1)：52．
34 Micheal J ,Saliba Jr. Heparin in the treatment of burns :A review[J ]. Burns ,2001 ,27(4) :3492358.
2．杭守云．LMWH对烧伤创面微循环影响的实验研究．皖南医学院学 报，2001，20：03．
3. Saliba Mj Jr ,Dempsey WC ,Kruggel JL.Large bums in humans ,treat2 ment with heparin[J ].J Am Med Assoc ,1973 ,225 :261.
4．陈玉林，黄康．创面愈合的评价指标．中国临床康复．2002，6(8)：1080-1081．
5．杨藻宸，主编．医用药理学．第3版．北京：人民卫生出版社，1997．518-520．
6．华云飞．肝素在烧伤治疗中的应用．中华实用医学．2004，6(6)：612．
7. Saliba MJ Jr. Heparin ,natre' s own burn remedy ? [J ] Emerg Med , 1973,106:111.
8. Macaig T ,luehlman T ,Friesel R , et al. Heparin binds endothelial cell growth factor ,the principal endothelial cell mitogen in bovine brain [J ]. Science, 1984 ,225:932.
9. Folkman J ,Shing Y. Control of angiogenesis by heparin and other sul2 fated polysaccharides[J ]. Adv Exp Med Biol ,1992 ,313 :3552364.
10. Azizkhan RG,Azizkhan JC ,Zetter BR , et al. Mast cell heparin stimu2 lates migration of capillary endothelial cells in vitro [J ]. J Exp Med , 1980,152:931.
11. Zapata2Sirvant RL ,Hansbrough JF , Greedleaf GE , et al. Reduction of bacterial translocation and intestinal structure alterations by heparin in a murine burn??injury model[J ].J Trauma ,1994 ,36 :126.
12. Gianotti L ,Alezander JW ,Fukushima R, et al. Reduction of bacteriatranslocation with oral fibroblast growth factor and sucrafate[J ]. Am J Surg, 1993 ,165:1952200.
13. Saliba MJ Jr. The effects and used of heparin in the care of burns thatimproves treatment and enhances the quality of life [J ]. Acta Chirur Plast,1997 ,39:13216.
14. Saliba MJ Jr ,Friner LA. Heparin efficac in burns. I . Significant early modification of experimental third2degree guines pig thermal burn[J ]. Aerosp Med,1970,41 :179.
15. Carr J . The anti2inflammatory action of heparin :heparin as an antago2 nistto histamine ,bradykinin ,and prostaglandin E1[J ]. Thromb Res , 1979,16:5072516.
16. Shanberge JN ,Kambayashi J ,Nakagawa M. The interaction of platelets with a tritium21abeled heparin[J]. Thromb Res ,1976,23 .-2642271.
17. Rent R ,Nyirman RRR ,Fiedel BA, et al. Potenitiation of Cl esteraseinhibitor activity by heparin [J ]. Clin Exp Immunol, 1976 ,23 : 2642 271.
18. Hiebert LM ,Lui JM. Heparin protects cultured arterial endothelial cells from damage by toxic oxygen metabolities[J ]. Arteriosclerosis ,1990 , 83 :37251.
19．张红兵．肝素在婴幼儿深度烧伤治疗中的作用．华北煤碳医学院学 报．2005，7(3)：288-289．
20. Lider O ,Bahav E ,Mekori YA , et al. Suppression of experimental auto2 immune diseases and prolongation of allograft survival by treating ani2 mals with??low doses of heparin[J ].J Clin Invest ,1989 ,83 :7522766.
21. Wright J G,Massop DW ,Rurst J G, et al. Pre2ischemic heparinizationdecreases rat skeletal muscke reperfusion injury [ J ]. J Cardiovasc Surg ,1991 ,32(sp): II. Abstract.
22. Sternberg WCⅢ,Makhoul RG,Adelman B. Heparin prevents postisch2 emic endothelial cell dysfunction by a mechanism independent of its an2 ticoagulant activity[J ].J Vasc Surg ,1993 ,17 :3182327.
23．罗攀，岑瑛，赵景华．肝素对Ⅱ度烧伤大鼠免疫功能的影响[J]．华西医 学，2000，15(1)：32233．
24．严小蓉，罗攀，岑瑛．肝素对深Ⅱ度烧伤大鼠的影响[J]．中华烧伤杂 志，2001，17(3)：1742176．
25. Ramakrishanan KM ,Babu M ,Tamachandran K. Effects of heparin oncollagen in burns[C]. Int Trans of the Plastic and Reconstructive Sur2 gery Congress. Montreal ,Canada ,1984.
1. Glucosanminoglycans. In :Burns :Multi2Center Update [ C]. Proc 10th Congr of International Society for Burn Injuries.Jerusalem. Israel ,125 November ,1998. Abstracts.
2 Saliba MJ Jr ,edit. The Effects of Heparin in the Treatment of Burn[C]. Int Meet ,24227. 1994 ,San Diego ,CA.
3 Elrod PD ,McCIeary RS ,Ball OT. An experimental study of the effect of heparin on survival time following lethal bruns[J ]. Surg Gyn Ob2 stet, 1951,92:35242.
4 Green BE ,Artz CP. An appraisal of heparin in burns : experimental study[J ]. Surg Forum ,1959 ,10 :343.
5 Saliba MJ Jr. Heparin in the treatment of burns[J ].J Am Med Assoc , 1967,200:650.
6 Saliba MJ Jr. Heparin efficacy in burns. II . Human thermal burn treatment which large doses of tipcal and parenteral heparin[J ]. Aero2 sp Med, 1970 ,41 :1302.
7 Saliba Mj Jr ,Dempsey WC ,Kruggel JL.Large burns in humans ,treat2 ment with heparin[J ].J Am Med Assoc ,1973 ,225 :261.
8 Saliba MJ Jr. Heparin ,natre' s own burn remedy ? [J ] Emerg Med , 1973,106:111.
9 杭守云．LMWH对烧伤创面微循环影响的实验研究[J]．皖南医学院学报，2001，20：03．
10 Macaig T ,luehlman T ,Friesel R , et al. Heparin binds endothelial cell growth factor ,the principal endothelial cell mitogen in bovine brain [J]. Science,1984,225:932.
11 Folkman J ,Shing Y. Control of angiogenesis by heparin and other sul2 fated polysaccharides[J]. Adv Exp Med Biol ,1992 ,313 :3552364.
12 Azizkhan RG,Azizkhan JC ,Zetter BR , et al. Mast cell heparin stimu2 lates migration of capillary endothelial cells in vitro[J]. J Exp Med , 1980 ,152 :931.
13 Zapata2Sirvant RL ,Hansbrough JF , Greedleaf GE , et al. Reduction of bacterial translocation and intestinal structure alterations by heparin in a murine burn injury model[J].J Trauma ,1994 ,36 :126.
14 Gianotti L ,Alezander JW ,Fukushima R , et al. Reduction of bacteria translocation with oral fibroblast growth factor and sucrafate[J]. Am J Surg, 1993 ,165:1952200.
15 Saliba MJ Jr. The effects and used of heparin in the care of burns that improves treatment and enhances the quality of life [J]. Acta Chirur Plast,1997 ,39:13216.
16 Saliba MJ Jr ,Friner LA. Heparin efficac in burns. I . Significant early modification of experimental third2degree guines pig thermal burn[J]. Aerosp Med,1970 ,41 :179.
17 Carr J . The anti2inflammatory action of heparin :heparin as an antago2 nist to histamine ,bradykinin ,and prostaglandin E1[J]. Thromb Res , 1979 ,16 :5072516.
18 Shanberge JN ,Kambayashi J ,Nakagawa M. The interaction of platelets with a tritium21abeled heparin[J ]. Thromb Res ,1976 ,23 :2642271.
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