Creation of a rat lymphedema model using extensive lymph node dissection and circumferential soft tissue resection: Is this a reliable model?

Abstract

The medical demand for lymphedema treatment is huge since the disease mechanism remains unclear, and management are difficult. Our purpose was to develop a reliable lymphedema model mimicking the clinical scenario and allows a microsurgical approach. Male Lewis rats weighing 400 to 450 g were used to create lymphedema with groin and popliteal lymph node dissection and creation of 5 mm circumferential skin defect (n=6). A skin incision was made and closed primarily for control group (n=5). Evaluation included indocyanine green (ICG) lymphangiography 1 and 2months postoperatively, volume difference between bilateral hindlimbs measured using micro-CT, and the skin was harvested for histological evaluation 2months postoperatively. Larger volume differences present in the lymphedema group (17.50 ± 7.76 vs. 3.73 ± 2.66%, p < .05). ICG lymphangiography indicated dermal backflow only in the lymphedema group. Increased thickness of the epidermis was noted in lymphedema group (28.50 ± 12.61 μm vs. 15.10 ± 5.41 μm, p < .0001). More CD45+ (35.6 ± 26.68 vs. 2.8 ± 4.23 cells/high power field [HPF], p < .0001), CD3+ (38.39 ± 20.17 vs. 9.73 ± 8.62 cells/HPF, p < .0001), and CD4+ cell infiltration (11.7 ± 7.71 vs. 2.0 ± 2.67 cells/HPF, p < .0001) were observed in the lymphedema group. Collagen type I deposition was more in the lymphedema group (0.15 ± 0.06 vs. 0.07 ± 0.03, p < .0005). A rat lymphedema model was successfully established. The model can be applied in lymphedema related research.