Neuromuscular Blocking Agent Cisatracurium Attenuates Lung Injury by Inhibition of Nicotinic Acetylcholine Receptor-α1.

Abstract

BACKGROUND:

Neuromuscular blocking agents (NMBAs) bind the nicotinic acetylcholine receptor α1 (nAChRα1) 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 nAChRα1.

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 PaO2 (140 ± 54, 209 ± 46, 269 ± 31, and 269 ± 54 mmHg, respectively, P < 0.05), and decreased the plasma levels of tumor necrosis factor-α (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 nAChRα1 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 nAChRα1.

• Authors: Vito Fanelli, Yasumasa Morita, Paola Cappello, Mirna Ghazarian, Bina Sugumar, Luisa Delsedime, Jane Batt, V Marco Ranieri, Haibo Zhang, Arthur S Slutsky
• Journal: Anesthesiology (Anesthesiology) Vol. 124 Issue 1 Pg. 132-40 (Jan 2016) ISSN: 1528-1175 [Electronic] United States
• PMID: 26540149 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Neuromuscular Blocking Agents
• Receptors, Nicotinic
• Atracurium
• cisatracurium

Topics

• Analysis of Variance
• Animals
• Atracurium (analogs & derivatives, pharmacology)
• Disease Models, Animal
• Inflammation (complications, prevention & control)
• Lung Injury (complications, prevention & control)
• Male
• Mice
• Mice, Inbred C57BL
• Neuromuscular Blocking Agents (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptors, Nicotinic (drug effects)