PULMONARY CAPILLARY TRANSPORT FUNCTION FROM FLOW-LIMITED INDICATORS

The objective of this study was to examine the use of rapidly diffusin g (flow-limited) indicators for estimating the pulmonary capillary blo od volume (i.e., fraction of the lung blood volume wherein the diffusi ble indicators equilibrate with the tissue) and the capillary transit time distribution. Supporting theory and an application to experimenta l data are presented. The theory leads to the following equations, whi ch relate the mean transit time (($) over bar t), the variance (sigma( 2)), and the third central moment (m(3)) of the capillary transport fu nction, h(c)(t), to the moments of the venous concentration-time curve s for a vascular reference indicator, C-R(t), and a flow-limited diffu sible indicator, C-D(t), after a bolus injection of the indicators ups tream from an organ: sigma(D)(2), - sigma(R)(2) = {[1 + (($) over bar t(e)/($) over bar t(c))](2) - 1}sigma(c)(2) and m(D)(3) - m(R)(3) = {[ 1 + (($) over bar t(e)/($) over bar t(c))](3) - 1}m(e)(3), where t(e) = ($) over bar t(D) - ($) over bar t(R) and ($) over bar t(c) is capil lary ($) over bar t. The moments of h(c)(t) can be estimated if the in jected bolus includes, along with the vascular reference indicator, at least two flow-limited diffusible indicators, each with a different ( $) over bar t(e). A least-squares optimization procedure can then be u sed to specify the moments of h(c)(t). This approach was applied to is olated dog lung lobes with [C-14]diazepam as the diffusible indicator. The tissue-to-perfusate partition coefficient for [C-14]diazepam coul d be adjusted to any desired value by altering the perfusate albumin c oncentration. Thus, by making a number of injections, each at a differ ent perfusate albumin concentration, data were obtained in a manner eq uivalent to making one injection with a number of flow-limited diffusi ble indicators, each with a different ($) over bar t(e). On average, t he estimated capillary volume and mean transit time were similar to 48 % of the total lobar volume and mean transit time, and the relative di spersion of the h(c)(t) was similar to 75%.