Use of diazepam for interpreting changes in extravascular lung water

Estimates of extravascular lung water volume (Q(ew)) by use of the multiple indicator-dilution method with a hydrophilic indicator such as tritiated water, along with a vascular reference indicator, depend not only on tissue hydration but also on tissue perfusion. Separation of these effects might be facilitated if both hydrophilic and lipophilic indicators were used, with the assumption that the extravascular volume accessible to the lipophilic indicator would be independent of hydration. We found that in isolated perfused dog lung lobes the extravascular volume accessible to the lipophilic amine [¹⁴C]diazepam (Q(ed)) was inversely proportional to the albumin concentration of the perfusate. This suggested that while the bolus was in the lungs, only a small fraction of the diazepam was in the aqueous phase of either lung tissue or perfusate. Changing the flow rate over a fairly wide range had little influence on the pattern of the tritiated water or [¹⁴C]diazepam effluent concentration curves when time was normalized to the lobar mean transit time. This suggests that the association of the diazepam with both the plasma albumin and the lipoid fraction of the tissue was in very rapid equilibrium on the time scale of a single pass through the lung lobe and that there was little barrier to its diffusion to and from the tissue. When the extravascular water volume was increased by either raising the hydrostatic pressure or instilling saline into the airways, both Q(ew) and Q(ew)/Q(ed) increased. When parts of the vascular bed in the edematous lobes were obstructed by injection of glass microspheres, Q(ew) decreased to values that were often less than in the normal nonedematous condition, but the Q(ew)/Q(ed) remained elevated. These results suggest that under these conditions an increase in Q(ew)/Q(ed) indicated edema around perfused vessels even when the measured Q(ew) decreased due to a concomitant decrease in the fraction of the lung tissue that was perfused.