  Isothermal rebreathing has been proposed as an experimental technique for
estimating the alveolar levels of hydrophilic volatile organic compounds (VOCs)
in exhaled breath. Using the prototypic test compound acetone we demonstrate
that the end-tidal breath profiles of such substances during isothermal
rebreathing show characteristics that contradict the conventional pulmonary
inert gas elimination theory due to Farhi. On the other hand, these profiles
can reliably be captured by virtue of a previously developed mathematical model
for the general exhalation kinetics of highly soluble, blood-borne VOCs, which
explicitly takes into account airway gas exchange as major determinant of the
observable breath output.
  This model allows for a mechanistic analysis of various rebreathing protocols
suggested in the literature. In particular, it clarifies the discrepancies
between in vitro and in vivo blood-breath ratios of hydrophilic VOCs and yields
further quantitative insights into the physiological components of isothermal
rebreathing.
