Abstract | BACKGROUND: 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.
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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)
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Chemical References |
- Neuromuscular Blocking Agents
- Receptors, Nicotinic
- Atracurium
- cisatracurium
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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)
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