Optical monitoring of microlymphatic disturbances during experimental lymphedema.

BACKGROUND: Rat mesentery has been widely used to study microvascular functions. The goal of this work is to extend this animal model to monitor blood and lymph microvessel function during lymphedema. METHODS AND
RESULTS: Lymphedema is created by microsurgical removal of regional lymph nodes (lymphadenectomy) or ligation of the collecting vein. Water volume in mesenteric tissue, microvessel diameters, phasic contraction, valve function, lymph flow velocity, and cell migration were analyzed during lymphedema development. Dynamic observation of water amount after lymphadenectomy revealed increasing edema from 30 min to 1 week; greatest degree of edema at one week, and gradual decrease in edema from 1 to 11 weeks. These effects were accompanied by acute constriction of lymph vessels and slowing of lymph flow velocity, switching to dilation and appearance of new blood capillaries at week 1, progressing to dilation and degenerative changes of the microlymphatic wall at week 4, and, finally, leading to lymphatic fibrosis and lymphangiogenesis at week 11. Acute venous insufficiency (30 min after vein ligation) led to significant edema, decreasing blood flow velocity to stasis, and output of erythrocytes from venules to interstitium, with further movement to microlymphatics and regional lymph nodes.
CONCLUSIONS: Rat mesentery as an animal model in combination with an advanced optical imaging system is valuable in studying microlymphatic disturbances in mesentery during the development of experimental lymphedema from latent period to chronic stages, including monitoring of individual cell dislocation with high resolution optical imaging.