Accession Number:

ADA285074

Title:

Development of an In Vitro Model Assay System for the Evaluation of the Effects of Toxic Chemicals on Human Airways

Descriptive Note:

Final rept.

Corporate Author:

ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD

Report Date:

1994-03-01

Pagination or Media Count:

16.0

Abstract:

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.

Subject Categories:

  • Medicine and Medical Research
  • Pharmacology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE