Lee R C, River L P, Pan F S, Ji L, Wollmann R L
Department of Surgery, University of Chicago, IL 60637.
Proc Natl Acad Sci U S A. 1992 May 15;89(10):4524-8. doi: 10.1073/pnas.89.10.4524.
Victims of major electrical trauma frequently suffer extensive skeletal muscle and nerve damage, which is postulated to be principally mediated by electroporation and/or thermally driven cell membrane permeabilization. We have investigated the efficacy of two blood-compatible chemical surfactants for sealing electroporated muscle membranes. In studies using cultured skeletal muscle cells, poloxamer 188 (P188; an 8.4-kDa nonionic surfactant) blocks, and neutral dextran (10.1 kDa) substantially retards, carboxyfluorescein release from electropermeabilized cell membranes. To test whether P188 administered intravenously could have the same therapeutic effect in vivo, the rat biceps femoris muscle flap attached by its arteriovenous pedicle was electropermeabilized until its electrical resistivity dropped to 50% of the initial value. P188 (460 mg/kg) administered intravenously 20 min postshock restored the resistivity to 77% of the initial value. When P188 was administered intravenously 5 min before shock, a dose-dependent impedance recovery rate was observed. Neither neutral dextran (460 mg/kg) nor sterile saline was effective. Histopathologic studies indicated that postshock poloxamer administration reduced tissue inflammation and damage in comparison with dextran-treated or control tissues. Electrophysiologic evidence of membrane damage was not observed in flaps of animals pretreated with poloxamer. These results suggest that it may be possible to seal in vivo tissue membranes injured by electrical, thermal, or other membrane-damaging forces.
严重电创伤的受害者经常遭受广泛的骨骼肌和神经损伤，据推测这主要是由电穿孔和/或热驱动的细胞膜通透性改变介导的。我们研究了两种血液相容性化学表面活性剂对电穿孔肌肉膜的封闭效果。在使用培养的骨骼肌细胞的研究中，泊洛沙姆188（P188；一种8.4 kDa的非离子表面活性剂）可阻止，而中性葡聚糖（10.1 kDa）可显著延缓羧基荧光素从电通透化细胞膜中释放。为了测试静脉注射P188在体内是否能产生相同的治疗效果，通过动静脉蒂连接的大鼠股二头肌肌瓣被电通透化，直到其电阻下降到初始值的50%。电击后20分钟静脉注射P188（460 mg/kg）可使电阻恢复到初始值的77%。当在电击前5分钟静脉注射P188时，观察到剂量依赖性的阻抗恢复率。中性葡聚糖（460 mg/kg）和无菌生理盐水均无效。组织病理学研究表明，与葡聚糖处理的组织或对照组织相比，电击后给予泊洛沙姆可减轻组织炎症和损伤。在接受泊洛沙姆预处理的动物的肌瓣中未观察到膜损伤的电生理证据。这些结果表明，有可能封闭因电、热或其他膜损伤力而受损的体内组织膜。
