股动脉靶向输入低温液体对兔下肢深Ⅱ度烫伤的保护作用
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摘要
【背景】
烧伤创面的冷疗(BCT)自古有之,公元1世纪已有人提出冷疗止痛。所谓冷疗是指:置烧伤部位于相对低温的环境中,使烧伤局部因冷却而达到治疗目的。历史上Galen(公元前129-199年),Rhazes(公元前852-923年),Earle(1799年)和Sorensen(1967年)均撰文推荐应用冷疗于烧伤创面。1987年英国烧伤学会推荐将冷疗作为烧伤急救的首选措施,目前冷疗已经成为国内外首选的最为重要的烧伤现场急救及早期救治措施之一。大量研究表明,冷疗能迅速降低局部温度,减轻疼痛;冷疗能预防创面的进一步加深;冷疗可抑制炎性介质;冷疗能降低局部组织的代谢,减少氧耗;冷疗能使局部血管收缩,减轻水肿。
但是作为一种强的物理刺激,冷疗治疗也存在一定的局限性:长时间的冷疗治疗在一定程度上影响着患者的循环功能,因此对于循环功能本来就比较脆弱的大面积病人、老人、小儿,传统认为并不适合该治疗;同时也有研究提出过长时间冷疗、延迟冷疗(DCT)、过度冷疗(ECT)有可能造成局部组织的冻伤;另外电击伤病人能否冷疗及如何冷疗尚无定论。因此虽然早期冷疗确实有效,但是临床上有大量的病人被作为了冷疗禁忌,从某种意义上讲该类患者丧失了一次有效的治疗机会。
经特定动脉靶向注入药物从而选择性治疗动脉支配范围组织病变的技术在肝胆外科,肿瘤科,放射治疗科已经发展的相当成熟。该技术不但可以减少药物总的使用剂量,提高起效药物数量,而且可以在很大程度上减少药物对其它组织或器官功能的影响。烧伤病人尤其是大面积烧伤病人多需要进行股动脉血气分析检查,如果选择其作为靶向治疗通道就可能实现注入小剂量低温液体,有效的降低其支配范围烧烫伤组织的温度。同时我们在临床中也观察到:大面积烧伤病人快速输入大量4℃血浆后,尚未发生不良并发症。
基于此,本研究通过建立兔下肢烫伤模型,采用动态测温技术,将过去认为不适合冷疗的低温液体于伤后通过股动脉小剂量,快速注入,观察低温液体的降温效果及热损伤保护作用;降温液体对创面愈合的影响做初步的评判。同时建立细胞烫伤模型,研究冷液体对烫伤后血管内皮细胞及成纤维细胞的继续熟损伤的影响。
【目的】
针对上述传统认为不适合冷疗的患者,探讨在其伤后30min和60min股动脉输入0～4℃低温液体进行冷疗对创面保护的有效性。为新治疗措施在大体和细胞水平进行机理的初步阐述。
【方法】
1)制作适合试验使用的温度巡检仪,其特点包括:便于消毒,体积小;能实现多通道同时检测;可动态检测;软件部分可进行简单数据处理。
2)筛选制作兔下肢深Ⅱ度烫伤模型条件,利用海伦-秦九韶(HQJF)公式法计算出兔下肢面积。
3)利用制作模型和温度巡检仪,验证股动脉输入低温液体的有效性。并通过病理观察、激光多普勒血流仪(LDPI)、彩色超声多普勒(CDFI)、扫描电子显微镜(SEM)技术对其机理进行阐述
4)筛选离体热损伤血管内皮细胞模型
5)利用热损伤模型,观察不同时间点予以低温液体对热继续损伤的影响。
【结果】
1)设计制作出的温度巡检仪:体积小(φ:0.5mm),测温精度高(和国家二级标准水银温度计相比误差±0.1℃),分辨率达到试验要求(0.1℃)。材质能耐受高温高压消毒,适合试验使用。数据传输稳定,软件记录数据准确。
2)计算出兔双下肢占体表面积比例为18%;筛选出制作兔下肢深Ⅱ度烫伤模型的关键是浸烫条件:70℃,10S。
3)烫伤后早期皮下及深部组织血管明显扩张,创面稳定后可见组织中炎性细胞浸润和血管中出现大量的红细胞聚集。超微结构可见血管内皮细胞的分层剥脱。
4)动态温度描记发现,烫伤后动物肢体皮下温度和深部组织温度呈分离现象:浸烫时兔下肢皮下温度及深部组织温度立即上升,最高达62.2℃,温度上升时间为:12.8±0.6S,深部组织温度较皮下温度延迟2.8±0.3s开始升高,深部组织温度最高达44.2℃,深部组织温度上升总时间为:12.8±0.4S;经过54±8min后皮下,深部组织温度降至伤前水平,此时深部组织温度和伤前相反,高于皮下温度。同时研究发现浅层的皮下温度容易受到环境变化的影响。
低温液体及冷敷料均有降温效果,注射低温液体与用冷敷料相比,深部组织温度下降幅度(2.8±0.3℃)明显大于后者。且降温后深部组织温度和不处理组相比,低于(或等于)皮下温度。而冷敷料降温后深部组织温度虽然有下降,但是下降幅度较小(13±0.4℃)。冷敷料组皮下温度下降幅度(2.5±0.1℃)和低温液体温度下降幅度(2.6±0.2℃)无明显差异(p＞0.05)。
LDPI结果显示烫伤后创面血流立即增加(p＜0.01),1小时后血流开始减少,24小时血流减少和伤前有显著差异(p＜0.05)。30min低温液体干预组明显抑制了早期血流的剧烈增加(6h内),24h时治疗组血流明显较对照组血流丰富。
病理结果显示:干预组可明显减轻肢体肿胀,降低创面感染率,加快伤后被毛的生长。HE染色显示:烫伤后小动脉,毛细血管明显立即扩张,血流增加,局部渗出增加,组织间隙增大,组织变疏松。伤后24小时组织内可见炎性细胞浸润。给予低温液体干预后,组织内扩张血管数量明显减少;而冷敷料组,深部组织血管扩张无显著减少。干预组都能明显减少局部组织的炎性细胞浸润。
CDFI结果显示烫伤后兔下肢血管明显扩张,血液流速加快,阻力指数下降(其中阻力指数以Vmin升高幅度大于Vmax)。给予低温液体后有一定的缩血管作用,血管直径明显下降,血流动力学指标有一定的纠正。
电子显微镜(SEM)观察处理前后血管内皮细胞变化显示:烫伤后血管内皮细胞受损明显,大量血管内皮细胞呈分层状剥脱,低温液体和冷敷料干预组血管内皮细胞病理损伤改变轻。30min干预组血管内皮细胞损伤明显轻于60min干预组。
烫伤兔足动脉输入低温液体后可以迅速降低皮下及深部组织温度,可以明显减轻肢体水肿,渗出减少,创面加深率明显降低,镜下见组织水肿和血管扩张受到明显的抑制;超微结构见血管内皮细胞损伤较对照组减轻。
1)筛选出制作热损伤ECV-304细胞模型条件:55℃20min作为血管内皮细胞热损伤条件,能达到约1/4左右数量的细胞死亡。
2)热损伤后早期冷液体处理可以降低热对血管内皮细胞,成纤维细胞的继续损伤,加速成纤维细胞向肌成纤维细胞的分化。
【结论】
低温液体注入和动脉血液混合后作为降温液体,不但可以减少冷疗液体使用量,而且可以保护循环功能,股动脉靶向输入低温液体对于目前临床部分不适合冷疗的患者有潜在应用临床价值。
[Objective]
To investigate the cooling and protective effects of a new modality:Low temperature Liquid(0-4℃) was intra-arterial injected 30mins to 60 mins after deepⅡscald of rabbits hind limbs through femoral artery,examined the cooling and protective effects and study the machnism of this method,hoping to offer a new clue of burn first aid cooling therapy,especially for the patients who suffered deep burns of limbs and regarded as the cases unsuitable for cooling treatment up to date.
[Methods]
120 New Zealand white rabbits wereused in this experiments.After anesthetigation,,standardized deep second degree scald of rabbit's hind limbs with TBSA 18%were made with the hind limbs immersed in 70℃water for 10 seconds and grouped into five groups randomly.GroupⅠand 2,20ml Low temperature liquid(4.0±0.8℃) was injected with 1 ml per second through femoral artery targetedly to cool the injured limbs 30mins and 60 mins postburn respectively;Group 3 and 4,HD-L type hydrogel dressing(?) was applied on the injuried limb 30mins and 60mins repectively;Group 5 as control and on treatment post burn.
Subcutaneous and deep tissue temperatures of all wounds were monitored and recorded with we designed sepical temperature meter.Pre-scald during scalding and after scalding at regular intervals for 6 hrs post burn.The skin blood perfusion of each injured limbs was detected and recorded by Laser Doppler Perfusion Imagein(LDPI) and B-mode ultrasonic echo.The wound healing time and quality were observed and recorded.the specimens of the wounds were harversted for histological assessment and SEM(Scaning Electron Microscopy) examination.
[Results]
Effective cooling of the burn wound and an increased rate of wound healing was showed in both cooling methods.There are obviously significanct decreases(2.8±0.3℃) in artery injection groups than hydrogel groups decrease (1.3±0.4℃).While there is no obviously difference in both groups of subcutaneous temperature decreasing.LDPI and B-mode ultrasonic echo results show femoral artery injection and hydrogel dressing can obviously decrease the blood perfusion of skin especially in 30min group.Histological assessment at 21 days indicated more rapid healing in both the hydrogel dressing and artery injection burns compared with the controls group.The time of wound healing of treatment groups was earlier for 5±1days than that of control group.Hair growth appeared in each group.
[Conclusion]
This result indicates that for patients with burn injuries and traditional regarding as unfit for cooling treatment,artery injection of low temperature liquid within 30min to cool limb may be a potential new and effective means to reduce tissue damage and increase wound healing
烧伤创面的冷疗(BCT)自古有之,公元1世纪已有人提出冷疗止痛。所谓冷疗是指:置烧伤部位于相对低温的环境中,使烧伤局部因冷却而达到治疗目的。历史上Galen(公元前129-199年),Rhazes(公元前852-923年),Earle(1799年)和Sorensen(1967年)均撰文推荐应用冷疗于烧伤创面。1987年英国烧伤学会推荐将冷疗作为烧伤急救的首选措施,目前冷疗已经成为国内外首选的最为重要的烧伤现场急救及早期救治措施之一。大量研究表明,冷疗能迅速降低局部温度,减轻疼痛;冷疗能预防创面的进一步加深;冷疗可抑制炎性介质;冷疗能降低局部组织的代谢,减少氧耗;冷疗能使局部血管收缩,减轻水肿。
但是作为一种强的物理刺激,冷疗治疗也存在一定的局限性:长时间的冷疗治疗在一定程度上影响着患者的循环功能,因此对于循环功能本来就比较脆弱的大面积病人、老人、小儿,传统认为并不适合该治疗;同时也有研究提出过长时间冷疗、延迟冷疗(DCT)、过度冷疗(ECT)有可能造成局部组织的冻伤;另外电击伤病人能否冷疗及如何冷疗尚无定论。因此虽然早期冷疗确实有效,但是临床上有大量的病人被作为了冷疗禁忌,从某种意义上讲该类患者丧失了一次有效的治疗机会。
经特定动脉靶向注入药物从而选择性治疗动脉支配范围组织病变的技术在肝胆外科,肿瘤科,放射治疗科已经发展的相当成熟。该技术不但可以减少药物总的使用剂量,提高起效药物数量,而且可以在很大程度上减少药物对其它组织或器官功能的影响。烧伤病人尤其是大面积烧伤病人多需要进行股动脉血气分析检查,如果选择其作为靶向治疗通道就可能实现注入小剂量低温液体,有效的降低其支配范围烧烫伤组织的温度。同时我们在临床中也观察到:大面积烧伤病人快速输入大量4℃血浆后,尚未发生不良并发症。
基于此,本研究通过建立兔下肢烫伤模型,采用动态测温技术,将过去认为不适合冷疗的低温液体于伤后通过股动脉小剂量,快速注入,观察低温液体的降温效果及热损伤保护作用;降温液体对创面愈合的影响做初步的评判。同时建立细胞烫伤模型,研究冷液体对烫伤后血管内皮细胞及成纤维细胞的继续熟损伤的影响。
【目的】
针对上述传统认为不适合冷疗的患者,探讨在其伤后30min和60min股动脉输入0～4℃低温液体进行冷疗对创面保护的有效性。为新治疗措施在大体和细胞水平进行机理的初步阐述。
【方法】
1)制作适合试验使用的温度巡检仪,其特点包括:便于消毒,体积小;能实现多通道同时检测;可动态检测;软件部分可进行简单数据处理。
2)筛选制作兔下肢深Ⅱ度烫伤模型条件,利用海伦-秦九韶(HQJF)公式法计算出兔下肢面积。
3)利用制作模型和温度巡检仪,验证股动脉输入低温液体的有效性。并通过病理观察、激光多普勒血流仪(LDPI)、彩色超声多普勒(CDFI)、扫描电子显微镜(SEM)技术对其机理进行阐述
4)筛选离体热损伤血管内皮细胞模型
5)利用热损伤模型,观察不同时间点予以低温液体对热继续损伤的影响。
【结果】
1)设计制作出的温度巡检仪:体积小(φ:0.5mm),测温精度高(和国家二级标准水银温度计相比误差±0.1℃),分辨率达到试验要求(0.1℃)。材质能耐受高温高压消毒,适合试验使用。数据传输稳定,软件记录数据准确。
2)计算出兔双下肢占体表面积比例为18%;筛选出制作兔下肢深Ⅱ度烫伤模型的关键是浸烫条件:70℃,10S。
3)烫伤后早期皮下及深部组织血管明显扩张,创面稳定后可见组织中炎性细胞浸润和血管中出现大量的红细胞聚集。超微结构可见血管内皮细胞的分层剥脱。
4)动态温度描记发现,烫伤后动物肢体皮下温度和深部组织温度呈分离现象:浸烫时兔下肢皮下温度及深部组织温度立即上升,最高达62.2℃,温度上升时间为:12.8±0.6S,深部组织温度较皮下温度延迟2.8±0.3s开始升高,深部组织温度最高达44.2℃,深部组织温度上升总时间为:12.8±0.4S;经过54±8min后皮下,深部组织温度降至伤前水平,此时深部组织温度和伤前相反,高于皮下温度。同时研究发现浅层的皮下温度容易受到环境变化的影响。
低温液体及冷敷料均有降温效果,注射低温液体与用冷敷料相比,深部组织温度下降幅度(2.8±0.3℃)明显大于后者。且降温后深部组织温度和不处理组相比,低于(或等于)皮下温度。而冷敷料降温后深部组织温度虽然有下降,但是下降幅度较小(13±0.4℃)。冷敷料组皮下温度下降幅度(2.5±0.1℃)和低温液体温度下降幅度(2.6±0.2℃)无明显差异(p＞0.05)。
LDPI结果显示烫伤后创面血流立即增加(p＜0.01),1小时后血流开始减少,24小时血流减少和伤前有显著差异(p＜0.05)。30min低温液体干预组明显抑制了早期血流的剧烈增加(6h内),24h时治疗组血流明显较对照组血流丰富。
病理结果显示:干预组可明显减轻肢体肿胀,降低创面感染率,加快伤后被毛的生长。HE染色显示:烫伤后小动脉,毛细血管明显立即扩张,血流增加,局部渗出增加,组织间隙增大,组织变疏松。伤后24小时组织内可见炎性细胞浸润。给予低温液体干预后,组织内扩张血管数量明显减少;而冷敷料组,深部组织血管扩张无显著减少。干预组都能明显减少局部组织的炎性细胞浸润。
CDFI结果显示烫伤后兔下肢血管明显扩张,血液流速加快,阻力指数下降(其中阻力指数以Vmin升高幅度大于Vmax)。给予低温液体后有一定的缩血管作用,血管直径明显下降,血流动力学指标有一定的纠正。
电子显微镜(SEM)观察处理前后血管内皮细胞变化显示:烫伤后血管内皮细胞受损明显,大量血管内皮细胞呈分层状剥脱,低温液体和冷敷料干预组血管内皮细胞病理损伤改变轻。30min干预组血管内皮细胞损伤明显轻于60min干预组。
烫伤兔足动脉输入低温液体后可以迅速降低皮下及深部组织温度,可以明显减轻肢体水肿,渗出减少,创面加深率明显降低,镜下见组织水肿和血管扩张受到明显的抑制;超微结构见血管内皮细胞损伤较对照组减轻。
1)筛选出制作热损伤ECV-304细胞模型条件:55℃20min作为血管内皮细胞热损伤条件,能达到约1/4左右数量的细胞死亡。
2)热损伤后早期冷液体处理可以降低热对血管内皮细胞,成纤维细胞的继续损伤,加速成纤维细胞向肌成纤维细胞的分化。
【结论】
低温液体注入和动脉血液混合后作为降温液体,不但可以减少冷疗液体使用量,而且可以保护循环功能,股动脉靶向输入低温液体对于目前临床部分不适合冷疗的患者有潜在应用临床价值。
[Objective]
To investigate the cooling and protective effects of a new modality:Low temperature Liquid(0-4℃) was intra-arterial injected 30mins to 60 mins after deepⅡscald of rabbits hind limbs through femoral artery,examined the cooling and protective effects and study the machnism of this method,hoping to offer a new clue of burn first aid cooling therapy,especially for the patients who suffered deep burns of limbs and regarded as the cases unsuitable for cooling treatment up to date.
[Methods]
120 New Zealand white rabbits wereused in this experiments.After anesthetigation,,standardized deep second degree scald of rabbit's hind limbs with TBSA 18%were made with the hind limbs immersed in 70℃water for 10 seconds and grouped into five groups randomly.GroupⅠand 2,20ml Low temperature liquid(4.0±0.8℃) was injected with 1 ml per second through femoral artery targetedly to cool the injured limbs 30mins and 60 mins postburn respectively;Group 3 and 4,HD-L type hydrogel dressing(?) was applied on the injuried limb 30mins and 60mins repectively;Group 5 as control and on treatment post burn.
Subcutaneous and deep tissue temperatures of all wounds were monitored and recorded with we designed sepical temperature meter.Pre-scald during scalding and after scalding at regular intervals for 6 hrs post burn.The skin blood perfusion of each injured limbs was detected and recorded by Laser Doppler Perfusion Imagein(LDPI) and B-mode ultrasonic echo.The wound healing time and quality were observed and recorded.the specimens of the wounds were harversted for histological assessment and SEM(Scaning Electron Microscopy) examination.
[Results]
Effective cooling of the burn wound and an increased rate of wound healing was showed in both cooling methods.There are obviously significanct decreases(2.8±0.3℃) in artery injection groups than hydrogel groups decrease (1.3±0.4℃).While there is no obviously difference in both groups of subcutaneous temperature decreasing.LDPI and B-mode ultrasonic echo results show femoral artery injection and hydrogel dressing can obviously decrease the blood perfusion of skin especially in 30min group.Histological assessment at 21 days indicated more rapid healing in both the hydrogel dressing and artery injection burns compared with the controls group.The time of wound healing of treatment groups was earlier for 5±1days than that of control group.Hair growth appeared in each group.
[Conclusion]
This result indicates that for patients with burn injuries and traditional regarding as unfit for cooling treatment,artery injection of low temperature liquid within 30min to cool limb may be a potential new and effective means to reduce tissue damage and increase wound healing
引文
1 Lawrence JC. British Burn Association recommended first aid for burns and scalds. Burns Incl Therm Inj, 1987,13:153.
2 Davies JW. Prompt cooling of burned areas: a review of benefits and the effector mechanisms. Burns Incl Therm Inj, 1982,9:1-6.
3 Blomgren I, Eriksson E, Bagge U. Effect of cold water immersion on oedema formation in the scalded mouse ear. Burns Incl Therm Inj, 1982,9:17-20.
4 Jandera V, Hudson DA, de Wet PM, et al. Cooling the burn wound: evaluation of different modalites. Burns, 2000,26:265-70.
5 Sawada Y, Urushidate S, Yotsuyanagi T, et al. Is prolonged and excessive cooling of a scalded wound effective?. Burns, 1997,23:55-8.
6 Yunn-Hwa Ma, Ya-Wun Hsu, Yeu-Jhy Chang, et al. Intra-arterial application of magnetic nanoparticles for targeted thrombolytic therapy: A rat embolic model. Journal of Magnetism and Magnetic Materials, 2007,311:342-346.
7 Persianinov LS. Application of intra-arterial blood transfusions and medications in asphyxia; clinical and experimental aspects. Akush Ginekol (Mosk), 1956,32:17-24.
8 Reboul H, Laubry P, Vergoz L. Measurement, control and registration of blood pressure at the point of injection of a liquid in a cavity: application in arteriophlebography and therapeutic intra-arterial injections. Arch Mal Coeur Vaiss, 1953,46:845-8.
9 Maehara Y,Matsumoto M,Kawashima M,et al.Clinical application of intra-arterial digital subtraction angiography to abdominopelvic neoplasms.Rinsho Hoshasen,1988,33:889-94.
10 Kalinowski M,Tepe G,Schieber A,et al.Intra-arterial application of the ACE inhibitor ramipriI using a microperforated catheter for the prevention of neointimal proliferation after angioplasty in an animal model.Rofo,1998,169:532-6.
11 Cancio LC,Kuwa T,Matsui K,et al.Intestinal and gastric tonometry during experimental burn shock.Burns,2007.
12 Reper P,Van Bos R,Van Loey K,et al.High frequency percussive ventilation in burn patients:hemodynamics and gas exchange.Burns,2003,29:603 -8.
13 陈意生,史景全.烧伤病理学.重庆出版社,1992.6-7.
14 黎鳌.黎鳌烧伤学.上海:上海科技出版社,2001.38-48.
15 李迟,陈忠,等.冷却疗法治疗烧伤的止痛作用.中国疼痛医学杂志,2001,7:219-220.
16 黎鳌.烧伤治疗学.北京:人民卫生出版社,1997.196.
17 Lonnecker S,Schoder V.Hypothermia in patients with bum injuries:influence of prehospitai treatment.Chirurg,2001,72:164-7.
18 刘毅,陈璧.小鼠深二度烫伤创面局部冷疗的实验研究.兰州医学院学报,1999,25:39-41.
19 晏泽,肖能坎,刘春利.烧伤后一氧化氮、内皮素动态变化与烧伤的关系.医学综述,1999:180-183.
20 盛志勇,郭振荣.危重烧伤治疗与康复学.北京:科学出版社,2000.105-106.
21 Mazur P,Cole KW.Influence of cell concentration on the contribution of unfrozen fraction and salt concentration to the survival of slowly frozen human erythrocytes.Cryobiology,1985,22:509-36.
22 Fiser PS,Fairfull RW.Combined effect of glycerol concentration and cooling velocity on motility and acrosomal integrity of boar spermatozoa frozen in 0.5 ml straws.Mol Reprod Dev,1990,25:123-9.
23 张必明,熊平.多边形分解方法计算人体体表局部损伤面积.中国法医学杂志,2007,22:192-193.
24 Droog EJ,Steenbergen W,Sjoberg F.Measurement of depth of burns by laser Doppler perfusion imaging.Burns,2001,27:561-8.
25 Sun JS,Tsuang YH,Chen IJ,et al.An ultra-weak chemiluminescence study on oxidative stress in rabbits following acute thermal injury.Burns,1998,24:225-31.
26 Hiroto Y,Shimao S,Shimizu Y.Effects of scalding injury on the components of rabbit paw lymph.Burns Incl Therm Inj,1988,14:313-9.
27 李迟,于东宁,覃凤均,等.冷疗法对家兔深Ⅱ度烫伤创面微循环的改善作用.中华烧伤杂志,2004,20:105-106.
28 童亚林,缪洪城,朱金红.康肤霜促进兔深Ⅱ度烫伤创面愈合的实验研究.中华烧伤杂志,2003:26.
29 De Camara DL,Raine T,Robson MC.Ultrastructural aspects of cooled thermal injury.J Trauma,1981,21:911-9.
30 Raine TJ,Heggers JP,Robson MC,et al.Cooling the bum wound to maintain microcirculation.J Trauma,1981,21:394-7.
31 Boykin JV Jr,Eriksson E,Sholley MM,et al.Cold-water treatment of scald injury and inhibition of histamine-mediated burn edema.J Surg Res, 1981,31:111-23.
32 Venter TH,Karpelowsky JS,Rode H.Cooling of the burn wound:the ideal temperature of the coolant.Burns,2007,33:917-22.
33 Byers M,Tarmey NT.Consensus on the pre-hospital approach to Burns Patient Management.J R Army Med Corps,2004,150:225;author reply 225-6.
34 Pushkar NS,Sandorminsky BP.Cold treatment of burns.Burns Incl Therm Inj,1982,9:101-10.
35 J.Moserova,E.Behounkova,Z.Prouza.Subcutaneous temperature measurements in a thermal injury.Burns,1975,1:267-268.
36 Fajardo LF,Schreiber AB,Kelly NI,et al.Thermal sensitivity of endothelial cells.Radiat Res,1985,103:276-85.
37 程飚,付小兵,盛志勇,等.离体成纤维细胞热损伤模型制作的研究.中华创伤杂志,2002,18:391-393.
2 Davies JW. Prompt cooling of burned areas: a review of benefits and the effector mechanisms. Burns Incl Therm Inj, 1982,9:1-6.
3 Blomgren I, Eriksson E, Bagge U. Effect of cold water immersion on oedema formation in the scalded mouse ear. Burns Incl Therm Inj, 1982,9:17-20.
4 Jandera V, Hudson DA, de Wet PM, et al. Cooling the burn wound: evaluation of different modalites. Burns, 2000,26:265-70.
5 Sawada Y, Urushidate S, Yotsuyanagi T, et al. Is prolonged and excessive cooling of a scalded wound effective?. Burns, 1997,23:55-8.
6 Yunn-Hwa Ma, Ya-Wun Hsu, Yeu-Jhy Chang, et al. Intra-arterial application of magnetic nanoparticles for targeted thrombolytic therapy: A rat embolic model. Journal of Magnetism and Magnetic Materials, 2007,311:342-346.
7 Persianinov LS. Application of intra-arterial blood transfusions and medications in asphyxia; clinical and experimental aspects. Akush Ginekol (Mosk), 1956,32:17-24.
8 Reboul H, Laubry P, Vergoz L. Measurement, control and registration of blood pressure at the point of injection of a liquid in a cavity: application in arteriophlebography and therapeutic intra-arterial injections. Arch Mal Coeur Vaiss, 1953,46:845-8.
9 Maehara Y,Matsumoto M,Kawashima M,et al.Clinical application of intra-arterial digital subtraction angiography to abdominopelvic neoplasms.Rinsho Hoshasen,1988,33:889-94.
10 Kalinowski M,Tepe G,Schieber A,et al.Intra-arterial application of the ACE inhibitor ramipriI using a microperforated catheter for the prevention of neointimal proliferation after angioplasty in an animal model.Rofo,1998,169:532-6.
11 Cancio LC,Kuwa T,Matsui K,et al.Intestinal and gastric tonometry during experimental burn shock.Burns,2007.
12 Reper P,Van Bos R,Van Loey K,et al.High frequency percussive ventilation in burn patients:hemodynamics and gas exchange.Burns,2003,29:603 -8.
13 陈意生,史景全.烧伤病理学.重庆出版社,1992.6-7.
14 黎鳌.黎鳌烧伤学.上海:上海科技出版社,2001.38-48.
15 李迟,陈忠,等.冷却疗法治疗烧伤的止痛作用.中国疼痛医学杂志,2001,7:219-220.
16 黎鳌.烧伤治疗学.北京:人民卫生出版社,1997.196.
17 Lonnecker S,Schoder V.Hypothermia in patients with bum injuries:influence of prehospitai treatment.Chirurg,2001,72:164-7.
18 刘毅,陈璧.小鼠深二度烫伤创面局部冷疗的实验研究.兰州医学院学报,1999,25:39-41.
19 晏泽,肖能坎,刘春利.烧伤后一氧化氮、内皮素动态变化与烧伤的关系.医学综述,1999:180-183.
20 盛志勇,郭振荣.危重烧伤治疗与康复学.北京:科学出版社,2000.105-106.
21 Mazur P,Cole KW.Influence of cell concentration on the contribution of unfrozen fraction and salt concentration to the survival of slowly frozen human erythrocytes.Cryobiology,1985,22:509-36.
22 Fiser PS,Fairfull RW.Combined effect of glycerol concentration and cooling velocity on motility and acrosomal integrity of boar spermatozoa frozen in 0.5 ml straws.Mol Reprod Dev,1990,25:123-9.
23 张必明,熊平.多边形分解方法计算人体体表局部损伤面积.中国法医学杂志,2007,22:192-193.
24 Droog EJ,Steenbergen W,Sjoberg F.Measurement of depth of burns by laser Doppler perfusion imaging.Burns,2001,27:561-8.
25 Sun JS,Tsuang YH,Chen IJ,et al.An ultra-weak chemiluminescence study on oxidative stress in rabbits following acute thermal injury.Burns,1998,24:225-31.
26 Hiroto Y,Shimao S,Shimizu Y.Effects of scalding injury on the components of rabbit paw lymph.Burns Incl Therm Inj,1988,14:313-9.
27 李迟,于东宁,覃凤均,等.冷疗法对家兔深Ⅱ度烫伤创面微循环的改善作用.中华烧伤杂志,2004,20:105-106.
28 童亚林,缪洪城,朱金红.康肤霜促进兔深Ⅱ度烫伤创面愈合的实验研究.中华烧伤杂志,2003:26.
29 De Camara DL,Raine T,Robson MC.Ultrastructural aspects of cooled thermal injury.J Trauma,1981,21:911-9.
30 Raine TJ,Heggers JP,Robson MC,et al.Cooling the bum wound to maintain microcirculation.J Trauma,1981,21:394-7.
31 Boykin JV Jr,Eriksson E,Sholley MM,et al.Cold-water treatment of scald injury and inhibition of histamine-mediated burn edema.J Surg Res, 1981,31:111-23.
32 Venter TH,Karpelowsky JS,Rode H.Cooling of the burn wound:the ideal temperature of the coolant.Burns,2007,33:917-22.
33 Byers M,Tarmey NT.Consensus on the pre-hospital approach to Burns Patient Management.J R Army Med Corps,2004,150:225;author reply 225-6.
34 Pushkar NS,Sandorminsky BP.Cold treatment of burns.Burns Incl Therm Inj,1982,9:101-10.
35 J.Moserova,E.Behounkova,Z.Prouza.Subcutaneous temperature measurements in a thermal injury.Burns,1975,1:267-268.
36 Fajardo LF,Schreiber AB,Kelly NI,et al.Thermal sensitivity of endothelial cells.Radiat Res,1985,103:276-85.
37 程飚,付小兵,盛志勇,等.离体成纤维细胞热损伤模型制作的研究.中华创伤杂志,2002,18:391-393.