SURFACTANT-INDUCED SEALING OF ELECTROPERMEABILIZED SKELETAL-MUSCLE MEMBRANES INVIVO
SURFACTANT-INDUCED SEALING OF ELECTROPERMEABILIZED SKELETAL-MUSCLE MEMBRANES INVIVO
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DOI：
10.1073/pnas.89.10.4524
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发表时间：
1992-05-15
影响因子：
11.1
通讯作者：
WOLLMANN, RL
中科院分区：
文献类型：
--
作者：
LEE, RC;RIVER, LP;WOLLMANN, RL
严重电创伤的受害者经常遭受广泛的骨骼肌和神经损伤，这被认为主要是由电穿孔和/或热驱动的细胞膜透化介导的。我们研究了两种血液相容性化学表面活性剂用于密封电穿孔肌膜的功效。在使用培养的骨骼肌细胞的研究中，泊洛沙姆188（P188; 8.4 kDa的非离子表面活性剂）阻断，中性葡聚糖（10.1 kDa）基本上延迟，从电透化细胞膜释放羧基荧光素。为了测试静脉内施用的P188是否可以在体内具有相同的治疗效果，通过其动静脉蒂附着的大鼠股二头肌肌瓣被电渗透，直到其电阻率下降到初始值的50%。休克后20分钟静脉注射P188（460 mg/kg）使电阻率恢复到初始值的77%。当在休克前5分钟静脉注射P188时，观察到剂量依赖性阻抗恢复率。中性右旋糖酐（460 mg/kg）和无菌盐水均无效。组织学研究表明，与右旋糖酐处理或对照组织相比，休克后给予泊洛沙姆可减少组织炎症和损伤。在用泊洛沙姆预处理的动物的皮瓣中未观察到膜损伤的电生理证据。这些结果表明，它可能是可能的，以密封体内组织膜损伤的电力，热，或其他膜损伤力。
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.