Development of an In Vitro Model Assay System for the Evaluation of the Effects of Toxic Chemicals on Human Airways
ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
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The ability of the anticholinesterase agent soman to contract human bronchi was examined. Soman 1-2 uM had variable effects on human bronchi that had not been stimulated with an electric field stimulator EFS. In bronchi continuously stimulated by EFS 0.5 Hz, 1 ms, 12 V, soman produced contractions in all tissues examined 12 preparations from 9 humans. In tissues stimulated by EFS, the beta-adrenoreceptor agonist isoproterenol produced relaxations that were greater in magnitude than the contractions produced by soman. The duration of the isoproterenol induced relaxations was variable. Of 12 preparations studied, 3 showed no reversal of the relaxation within 120 min, 6 showed a slow reversal with a reversal time of 106 or - 6 min and 3 showed rapid reversal with a 50 reversal time of 14 min. In the latter group the duration of the relaxation produced by isoproterenol was doubled 28 or - 2 min by the M2 muscarinic receptor antagonist AFDX 116 10 uM. These results show that the isolated human bronchus is a useful model for studying the effects of toxic chemical agents such as soman on the airways. The data obtained with isoproterenol suggest that beta-2 agonists may be useful adjuncts for treating the effects of anticholinesterase agents.
- Medicine and Medical Research