How well mixed is inert gas in tissues?

Area of Science:

• Physiology
• Biophysics
• Pharmacokinetics

Background:

• Tissue inert gas washout typically follows multiexponential curves, deviating from expected monoexponential patterns in homogeneous compartments.
• This implies a relative dispersion (square root of variance to mean transit time ratio) greater than 1.
• Explanations like heterogeneous capillary flow or spacing have been proposed.

Purpose of the Study:

• To investigate the underlying mechanisms responsible for multiexponential inert gas washout curves in tissues.
• To determine if small-scale capillary heterogeneities can explain observed washout patterns.
• To propose a revised hypothesis for the observed phenomena.

Main Methods:

• Computer simulations of random walk of gas molecules in skeletal muscle capillary beds.
• Analysis of parameters including capillary flow, spacing, and countercurrent exchange.
• Simple diffusion and analytical calculations of gas molecule movement and vascular exit/entry points.

Main Results:

• Heterogeneity in adjacent capillaries, heterogeneous flow, variations in spacing, or small-scale countercurrent exchange could not account for the observed multiexponential washout or high relative dispersions.
• Gas molecules can diffuse several millimeters from their entry point.
• Inert gas molecules typically exit and re-enter the vasculature through vessels larger than 20 microns.

Conclusions:

• Small-scale capillary variations are insufficient to explain complex tissue inert gas washout.
• The multiexponential nature of washout curves is likely caused by heterogeneity between tissue regions separated by 3 mm or more.
• Countercurrent exchanges in vessels larger than 20 microns may also contribute significantly.