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Publication : Genetic susceptibility to atracurium-induced bronchoconstriction.

First Author  Levitt RC Year  1995
Journal  Am J Respir Crit Care Med Volume  151
Issue  5 Pages  1537-42
PubMed ID  7735612 Mgi Jnum  J:26585
Mgi Id  MGI:74029 Doi  10.1164/ajrccm.151.5.7735612
Citation  Levitt RC, et al. (1995) Genetic susceptibility to atracurium-induced bronchoconstriction. Am J Respir Crit Care Med 151(5):1537-42
abstractText  The goal of this study was to develop a murine model of atracurium-induced bronchoconstriction in which to evaluate the mechanism of action of this airway response. We evaluated nine inbred strains of mice for the development of atracurium-induced bronchoconstriction. The maximal difference in the magnitude of the airway response to atracurium noted between the highly responsive DBA/2 mice and the minimally responsive SJL mice was greater than 20-fold. This phenotype appears to reflect an intrinsic difference in the lungs of these animals because the extent of neuromuscular blockade was not significantly different in DBA/2 and SJL mice. Atracurium-induced airway hyperresponsiveness in DBA/2 mice was eliminated in a dose-dependent manner by pretreatment with atropine or pancuronium. These data are consistent with a postganglionic vagal efferent mechanism which produces a differential pulmonary response to this neuromuscular blocker. A genetic predisposition to atracurium-induced bronchoconstriction appears to exist in certain inbred strains of mice. Thus, a mouse model may be useful for mapping the gene(s) that control this trait and for suggesting responsible candidate genes. Our results suggest that the inbred laboratory mouse will be useful to study the mechanism by which atracurium produces bronchoconstriction.
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