Developing a Lower Limb Lymphedema Animal Model with Combined Lymphadenectomy and Low-dose Radiation

Abstract

Background: This study was aimed to establish a consistent lower limb lymphedema animal model for further investigation of the mechanism and treatment of lymphedema. Methods: Lymphedema in the lower extremity was created by removing unilateral inguinal lymph nodes followed by 20, 30, and 40 Gy (groups IA, IB, and IC, respectively) radiation or by removing both inguinal lymph nodes and popliteal lymph nodes followed by 20 Gy (group II) radiation in Sprague-Dawley rats (350–400 g). Tc99 lymphoscintigraphy was used to monitor lymphatic flow patterns. Volume differentiation was assessed by microcomputed tomography and defined as the percentage change of the lesioned limb compared to the healthy limb. Results: At 4 weeks postoperatively, 0% in group IA (n = 3), 37.5% in group IB (n = 16), and 50% in group IC (n = 26) developed lymphedema in the lower limb with total mortality and morbidity rate of 0%, 56.3%, and 50%, respectively. As a result of the high morbidity and mortality rates, 20 Gy was selected, and the success rate for development of lymphedema in the lower limb in group II was 81.5% (n = 27). The mean volume differentiation of the lymphedematous limb compared to the health limb was 7.76% ± 1.94% in group II, which was statistically significant compared to group I (P < 0.01). Conclusions: Removal of both inguinal and popliteal lymph nodes followed by radiation of 20 Gy can successfully develop lymphedema in the lower limb with minimal morbidity in 4 months.