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

Biagini RE; Moorman WJ; Lewis TR; Bernstein IL
Toxicol Appl Pharmacol 1985 Mar; 78(1):139-146
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.
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Toxicology and Applied Pharmacology
Page last reviewed: November 6, 2020
Content source: National Institute for Occupational Safety and Health Education and Information Division