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Pulmonary responsiveness to methacholine and disodium hexachloroplatinate (Na2PtCl6) aerosols in cynomolgus monkeys (Macaca fascicularis).

Authors
Biagini-RE; Moorman-WJ; Lewis-TR; Bernstein-IL
Source
Toxicol Appl Pharmacol 1985 Mar; 78(1):139-146
NIOSHTIC No.
00149130
Abstract
The association between airway cholinergic status and sodium- hexachloroplatinate (SHP) pulmonary reactivity was investigated in naive monkeys. Male Cynomolgus-monkeys were challenged bronchially with serially increasing concentrations of methacholine at concentrations from 0.1 milligram per milliliter (mg/ml) to 6.25mg/ml. Two to 3 weeks later the same animals were challenged with 0.5 to 50mg/ml solutions of SHP. The effects of these acute serial bronchial challenges on average pulmonary flow resistance, maximal expiratory flow volume (MEFV), dynamic compliance, and respiratory rates were determined. The correlation between the response of an individual animal to methacholine and subsequently to SHP was quite variable. Mean pulmonary flow resistance, dynamic compliance, and MEFV were not significantly altered over the interval between methacholine and SHP challenges. With both challenges, pulmonary flow resistance increased and dynamic compliance decreased in concentration dependent fashions. There were no statistically significant differences between these reactions to the two challenges. The respective non cumulative concentrations necessary for a 400 percent increase in post vehicle pulmonary flow resistance were: SHP, 23mg/ml; and methacholine, 2mg/ml. Regional pulmonary effects, central versus peripheral airways, were noted with both agents. Both agents produced dose dependent increases in MEFV. SHP challenge yielded significantly greater reductions in MEFV flow parameters at concentrations greater than 2.5mg/ml when compared to methacholine challenge effects. There were no statistically significant changes in respiratory rates observed with increasing bronchial challenge concentrations of either agent when compared to post challenge rates. The authors conclude that there are differential mechanisms of pharmacologic action of the bronchoconstrictive effects of these two compounds in monkeys. Methacholine pulmonary reactivity is not predictive of SHP reactivity in naive monkeys.
Keywords
NIOSH-Author; Metal-refining; Platinum-compounds; Industrial-chemicals; Medical-research; Animal-studies; Metallic-salts; Respiratory-hypersensitivity; Toxicology; Lung-function; Biological-effects; Physiological-measurements
CODEN
TXAPA9
Publication Date
19850330
Document Type
Journal Article
Fiscal Year
1985
NTIS Accession No.
NTIS Price
Issue of Publication
1
ISSN
0041-008X
NIOSH Division
DBBS
Source Name
Toxicology and Applied Pharmacology
State
OH
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