Solute transfer into the extravascular space: comparison of two non-invasive measurement techniques

Little clinical attention has been paid to the quantification of microvascular permeability to small hydrophilic solutes, probably because of a paucity of non-invasive techniques. We describe a technique using the gamma camera which measures the clearance of 99mTc DTPA, a molecule similar in size to sucrose, from the intravascular to the extravascular space in the lumbar tissues below the kidneys. This regional clearance (PSr) is analogous to the permeability-surface area (PS) product, a well established concept for describing solute transfer across the capillary. We found a value in subjects with normal renal function of 1.0 (SD 0.2) ml.min-1.100 ml-1 tissue, which is broadly similar to the values anticipated from published values of the extraction fraction of 51Cr EDTA and plasma flow of resting human skeletal muscle. We also describe an index, the t95, of whole body microvascular permeability. This is the time at which the second exponential of the bi-exponential plasma 99mTc DTPA clearance curve becomes equal to 95% of the total curve. The index reflects the rate of equilibration of DTPA between intravascular and extravascular spaces, and should reflect whole body microvascular permeability. The t95 showed a significant inverse correlation with regional clearance (t95 = -12 PSr + 98 min; r = -0.61; n = 60; p less than 0.001) confirming their mutual dependence on capillary DTPA transfer. These non-invasive techniques, with their advantages of simplicity, could prove useful in a variety of clinical settings.