Rossignol Benoit, Gueret Gildas, Pennec Jean-Pierre, Morel Julie, Rannou Fabrice, Giroux-Metges Marie-Agnès, Talarmin Hélène, Gioux Maxime, Arvieux Charles C
EA 3879, Unité de Physiologie Comparée et Intégrative, Brest-cedex 3, France.
Crit Care Med. 2008 Jun;36(6):1855-63. doi: 10.1097/CCM.0b013e318176106b.
Critical illness polyneuromyopathy has been extensively studied in various animal models regarding electrophysiological aspects or molecular mechanisms involved in its physiopathology; however, little data are available on its main clinical feature, that is, muscular weakness. We have studied the effects of chronic sepsis in rats with special consideration to contractile and neuromuscular blockade properties in relation with the level of messenger RNA (mRNA) coding for ryanodine and acetylcholine receptors.
This was an experimental animal study.
This study was conducted at a university laboratory.
Subjects consisted of Wistar rats.
Chronic sepsis was achieved by cecal ligation and needle perforation. Ten days after surgery, fast twitch extensor digitorum longus was excised for extraction and assays of mRNA coding for ryanodine and acetylcholine receptor subunits and contralateral muscle was tested in vivo on a mechanical bench. A fatigability index was measured and neuromuscular blockade properties using atracurium were evaluated.
A decrease in active force developed by extensor digitorum longus associated with an increase in passive force is induced by chronic sepsis. Maximal force at optimal length during twitch contraction was significantly reduced (0.25 +/- 0.09 N vs. 0.17 +/- 0.06 N); contraction and relaxation speeds were higher as shown by the decrease of respective time constants (3.75 +/- 0.01 msec vs. 2.70 +/- 0.0 msec, 10.76 +/- 0.03 msec vs. 7.62 +/- 0.03 msec) in the control group compared with the septic group. Fatigability index was significantly lower (23 +/- 0.11% vs. 59 +/- 0.19%) in septic rats. These rats also showed quicker blockade and shorter recovery after atracurium administration. Sepsis induced a significant increase of the expression of ryanodine receptor (RyR) RyR1 along with a steady expression of RyR3 mRNA, leading to a 5.6-fold increase of RyR1/RyR3 ratio with a steadiness of mRNA corresponding to acetylcholine-receptors.
Chronic inflammation and sepsis induced a decrease in contractile performances of extensor digitorum longus along with accelerated kinetics of atracurium possibly induced by modified expression of RyR1 receptors and not acetylcholine-receptors.
关于危重病性多神经病在其生理病理学中涉及的电生理方面或分子机制，已在各种动物模型中进行了广泛研究；然而，关于其主要临床特征即肌肉无力的数据却很少。我们研究了慢性脓毒症对大鼠的影响，特别考虑了与编码兰尼碱受体和乙酰胆碱受体的信使核糖核酸（mRNA）水平相关的收缩和神经肌肉阻滞特性。
这是一项实验性动物研究。
本研究在一所大学实验室进行。
对象为Wistar大鼠。
通过盲肠结扎和针刺穿孔造成慢性脓毒症。术后10天，切除快速收缩的趾长伸肌以提取和检测编码兰尼碱受体和乙酰胆碱受体亚基的mRNA，并在机械实验台上对侧肌肉进行体内测试。测量疲劳指数并评估使用阿曲库铵的神经肌肉阻滞特性。
慢性脓毒症导致趾长伸肌产生的主动力下降，同时被动力增加。抽搐收缩期间最佳长度时的最大力量显著降低（0.25±0.09牛与0.17±0.06牛）；与脓毒症组相比，对照组的收缩和舒张速度更高，这表现为各自时间常数的降低（3.75±0.01毫秒与2.70±0.0毫秒，10.76±0.03毫秒与7.62±0.03毫秒）。脓毒症大鼠的疲劳指数显著更低（23±0.11%与59±0.19%）。这些大鼠在给予阿曲库铵后还表现出更快的阻滞和更短的恢复时间。脓毒症导致兰尼碱受体（RyR）RyR1的表达显著增加，同时RyR3 mRNA表达稳定，导致RyR1/RyR3比值增加5.6倍，而与乙酰胆碱受体对应的mRNA保持稳定。
慢性炎症和脓毒症导致趾长伸肌的收缩性能下降，以及阿曲库铵动力学加速，这可能是由RyR1受体而非乙酰胆碱受体的表达改变所致。
