Inhalation of heavy metal oxides and salts as air pollutants associated with flyash and other particulate aerosols, presents toxicants at the airway surface of the lung. The absorption of these toxicants from the airway to the pulmonary circulation has been little studied and may be of importance in possible alterations of homestatic lung membrane functions. Most heavy metals are known to exert biological effects through combination with reactive groups on the membrane. The transport of ions across absorbing or excreting membranes is sensitive to the action of heavy metal ions. The mechanisms of removal of metal ions from the airways will be examined using intratracheal instillation and aerosol exposure in vivo and in vitro. Intact rats will be used as an in vivo model of inhalation while the isolated, ventilated and perfused rat lung will be used as an in vitro model. The kinetics of removal of each heavy metal ion will be measured and will characterize whether the removal process is active or facilitated transport or simple diffusion. Bidirectional versus unidirectional transport will be examined using the isolated and ventilated lung perfused through the arterial circulation with the metal cation and an intravascular marker. Possible alterations of a well defined carrier mediated transport system in the lung, phenol red, will be investigated. The effects of these toxicants on the release of vasoactive substances from the lung will be examined. These data will define the permeability of the lung to inhaled heavy metals, indicate potential toxic actions on the lung and probe potential interaction with the vascular regulatory action of the lung. These data will be of practical value in predicting the role of inhalation as a route of intoxication in man.
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