A lung model describing uptake of organic solvents and roles of mucosal blood flow and metabolism in the bronchioles.
A simple lung model (mucosal blood flow and metabolism model, MBM model) was developed to describe the uptake of organic solvents and investigate the role of mucosal blood flow and metabolism. The model separates the lung into four compartments, the peripheral bronchial tract (gas phase), the mucus layer lining the wall surface of the tract, the alveolar space (gas phase), and the alveolar blood. Solvent molecules are absorbed in the mucus layer during inhalation and released during exhalation. The deposited solvent diffuses radially into the mucosal tissue of the respiratory tract and transfers to the mucosal blood flow. To describe this behavior, a hypothetical mucosal blood flow throughout the mucus layer was used. The solvent in the mucosal tissue may be also metabolized, and a hypothetical metabolism in the mucus layer was used. The rate of the hypothetical mucosal blood flow was determined to be 5.2 ml/min based on the best fitting of previously obtained data for seven polar organic solvents. The MBM model predicts that as the blood-air partition coefficient (lambda(B)) increases from 0.1 to 20, the relative end-exhalation (E(end)) will decrease from 0.89 to 0.07, and as lambda(B) increases to 500, E(end) will increase to 0.33. After lambda(B) = 500, E(end) is predicted to decrease again, and at lambda(B) = 10000, E(end) is 0.09. The model also predicts that as lambda(B) increases from 0.1 to 10, the relative uptake (U) increases from 0.08 to 0.61, and as lambda(B) increases to 150, U decreases to 0.50. After lambda(B) = 150, U increases again, and at lambda(B) = 10,000, U is 0.8. The predictions show good agreement with values observed in human experimental studies. The MBM model predicts that uptake by the mucosal blood (U(Al)) would be equal to uptake by the alveolar blood (U(Mu)) at lambda(B) of 1000 and U(Al) is more than 90% of total uptake at lambda(B) > 10,000. The model also shows that U is significantly increased by the mucosal metabolism at lambda(B) between 50 and 5000. Especially, U in the case of CL(Mu) = 100 ml/min is higher by 0.3 than that in the nonmucosal metabolism.
Kumagai
S
S
Department of Occupational Health, Osaka Prefectural Institute of Public Health, 1-3-69, Nakamichi, Higashinari-ku, Osaka, 537 Japan. kumagai@iph.pref.osaka.jp.
Matsunaga
I
I
D000280:Administration, Inhalation; D000818:Animals; D015824:Blood-Air Barrier / Q000502:physiology; D001980:Bronchi / Q000098:blood supply / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008954:Models, Biological; D009930:Organic Chemicals / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D020545:Respiratory Mucosa / Q000098:blood supply* / Q000378:metabolism; D012995:Solubility; D012997:Solvents / Q000493:pharmacokinetics*; D013997:Time Factors
D009930:Organic Chemicals; D012997:Solvents