Creation of a Rat Lower Limb Lymphedema Model

Lymphedema is a frequent complication after surgical treatments of cancer involving lymph node resection. However, research of lymphedema treatments, such as vascularized lymph node transfer, is limited by the absence of an adequate lymphedema animal model. The purpose of this study was to determine if we could create sustainable lower limb lymphedema in the rat with a combination of inguinal lymphadenectomy, circumferential skin and subcutaneous tissue excision, and radiotherapy.

Inguinal lymphadenectomies were completed in 15 Sprague-Dawley rats. In cohort A, 5 rats received a 0.5- to 1.0-cm wide excision of proximal thigh skin and subcutaneous tissue. This step was omitted for the 10 rats in cohort B. Cohort A then received a single radiation dose of 22.7 Gy, whereas cohort B received a cumulative dose of 40.5 Gy. Bioimpedance measurements were obtained monthly to assess lymphedema progression, and lymphatic drainage at 6 months postradiation was visualized via indocyanine green (ICG) lymphangiography.

Two rats in cohort A developed visually appreciable lymphedema in the lower limb, with bioimpedance ratios of 0.684 and 0.542 and ankle circumference ratios of 1.294 and 1.061, respectively, consistent with lymphedema. Furthermore, ICG lymphangiography in these cohort A rats revealed impaired lower limb lymphatic drainage. In cohort B, however, bioimpedance and circumference ratios, and ICG lymphangiography, did not reveal abnormal lymphatic drainage.

The combination of inguinal lymphadenectomy, circumferential skin and subcutaneous tissue excision, and radiotherapy can successfully create lower limb lymphedema in the rat. When soft tissue excision is omitted, lymphedema does not develop.