Figure 9. Steady-State and Dynamic Effects of Lymphatic Drainage Rates (k_L).

Steady-state effects of k_L on VEGF and sVEGFR1 concentrations (A) and flows (B). Of the three transport parameters (k_P, k_L, k_CL), increasing k_L over two orders of magnitude about the control value resulted in the greatest fluctuations in steady-state concentrations: most significantly elevating plasma VEGF and sVEGFR1, while lowering interstitial sVEGFR1. Exceptions were noted with localized changes in k_L – e.g., with increasing only k_L,Normal from ‘CP’ to ‘PE’, the enhanced flushing of sVEGFR1 from the local interstitium into the plasma eventually spilled over through increased sVEGFR1 extravasation into the opposite compartment to elevate interstitial sVEGFR1 concentration there. In addition, a reversal in permeability flow of sVEGFR1-VEGF complex (red box) was noted for k_L above control. ‘Lo’ = low; ‘Nite’ = night; ‘+’ = supine awake (control); ‘SE’ = whole-body steady exercise; ‘CP’ = calf-only peak exercise; ‘PE’ = whole-body peak exercise; ‘Hi’ = high. Dynamic Effects of k_L on VEGF, sVEGFR1, and sR1-VEGF Concentrations (C). k_L-driven fluctuations in VEGF and sVEGFR1 attained within physiological diurnal cycles were less than those attained during steady-state analyses but still were of very wide ranges. “Bed-rest days” (purple columns) consisted of 15 hrs of wakefulness limited to supine or sitting postures, followed by 9 hrs of sleep. “Active days” (yellow columns) consisted of 15-hrs of activity starting off with a peak in k_L during early exercise and settling down to a steady running/walking rate, followed by 9 hrs of sleep. Reversed permeability flow of sVEGFR1-VEGF complex (red cross-hatching) was observed in the latter active waking hours. “Calf-limited activity days” (aqua column) are same as “bed-rest days” except that active k_L was induced in the calf during the first 15 hrs of wakefulness. Stick-figure illustrations adapted from Olszewski et al. Lymphology 1977, 10(3):178–183.