A New Experimental Lymphedema Model

Abstract

Background Our aim was to create a new rodent hind limb lymphedema model lacking the fibrosis effect induced by radiotherapy and subjected to the inhibition of lymphangiogenesis via sirolimus (rapamycin) to maintain a chronic lymphedema model and investigate its reliability for human treatment modalities. Methods Forty-two Sprague-Dawley rats were randomly assigned to 7 groups: (1) surgery control, (2) vehicle-surgery control, (3) vehicle control, (4) rapamycin control, (5) surgery with 1 mg/kg per day rapamycin, (6) surgery with 1.5 mg/kg per day rapamycin, and (7) surgery with 2 mg/kg per day rapamycin. All surgeries were performed on the right hind limbs, with the left hind limbs also considered as a control. The drug and its solvent were administered daily into the relevant groups intraperiteonally. The presence of lymphedema was investigated by weekly limb circumference measurements, microcomputed tomography, fluorescence lymphography using indocyanine green dye, and microscopic evaluation at the end of the sixth week to determine any histological changes in the hind limbs. Results In group 1, lymphedema was observed for 2 weeks (P = 0.032), whereas in groups 5, 6, and 7, lymphedema lasted for 3 weeks (P < 0.05.) Fluorescence using indocyanine green revealed that the edema was totally resolved after 6 weeks of surgery by a well-developed superficial lymphatic organization instead of the normal distinct vessel structure. Histologically, groups 1, 5, 5, and 7 demonstrated a significant increase in both the number of macrophages (P < 0.001) and newly formed lymphatic vessels in the right side surgically treated hind limb (P < 0.05). Conclusions Despite the extreme surgical destruction and lymphangiogenesis inhibition in the rat model, the sustained lymphedema did not last >3 weeks. Because of the rapid neolymphangiogenesis in murines and a different wound healing mechanism, they should not be considered as an appropriate model for research on human lymphedema in first place.

Impact of Cervical Lymphatic Obstruction on Brain Pathophysiology in Cervical Lymphedema Animal Models

“…In previous studies, the development of lymphedema in animal models was verified via limb circumference or thickness measurement 65,66 . In this study, changes in the cervical cross-sectional area were used to evaluate edema.…”