Neuromuscular Blocking Agent Cisatracurium Attenuates Lung Injury by Inhibition of Nicotinic Acetylcholine Receptor-alpha 1

作者：Fanelli Vito; Morita Yasumasa; Cappello Paola; Ghazarian Mirna; Sugumar Bina; Delsedime Luisa; Batt Jane; Ranieri V Marco; Zhang Haibo^*; Slutsky Arthur S

来源：Anesthesiology, 2016, 124(1): 132-140.

DOI：10.1097/ALN.0000000000000907

Background: Neuromuscular blocking agents (NMBAs) bind the nicotinic acetylcholine receptor alpha 1 (nAChR alpha 1) that also contributes to inflammatory signaling. Thus, the author hypothesized that the use of NMBA mitigates lung injury by improving ventilator synchrony and decreasing inflammatory responses.
Methods: Lung injury was induced by intratracheal instillation of hydrogen chloride in rats that were randomized to receive no NMBA with evidence of asynchronous ventilation (noNMBA/aSYNC, n = 10); no NMBA with synchronous ventilation (noNMBA/SYNC, n = 10); cisatracurium (CIS, n = 10); or pancuronium (PAN, n = 10). Mechanical ventilation was set at a tidal volume of 6 ml/kg and positive end-expiratory pressure 8 cm H2O for 3 h. Human lung epithelial, endothelial, and CD14(+) cells were challenged with mechanical stretch, lipopolysaccharide, lung lavage fluids (bronchoalveolar lavage fluid), or plasma obtained from patients (n = 5) with acute respiratory distress syndrome, in the presence or absence of CIS or small-interfering RNA and small hairpin RNA to attenuate the cell expression of nAChRa1.
Results: The use of CIS and PAN improved respiratory compliance (7.2 +/- 0.7 in noNMBA/aSYNC, 6.6 +/- 0.5 in noNMBA/SYNC, 5.9 +/- 0.3 in CIS, and 5.8 +/- 0.4 cm H2O/l in PAN; P < 0.05), increased Pao(2) (140 +/- 54, 209 +/- 46, 269 +/- 31, and 269 +/- 54 mmHg, respectively, P < 0.05), and decreased the plasma levels of tumor necrosis factor-alpha (509 +/- 252 in noNMBA, 200 +/- 74 in CIS, and 175 +/- 84 pg/ml in PAN; P < 0.05) and interleukin-6 (5789 +/- 79, 1608 +/- 534, and 2290 +/- 315 pg/ml, respectively; P < 0.05). The use of CIS and PAN or silencing the receptor nAChRa1 resulted in decreased cytokine release in the human cells in response to a variety of stimuli mentioned earlier.
Conclusions: The use of NMBA is lung protective through its antiinflammatory properties by blocking the nAChRa1. (Anesthesiology 2016; 124:132-40)

• 出版日期2016-1