Experimental evaluation of dermal lymphatics in preservation of lymphatic function

BACKGROUND: Secondary lymphedema is characterized by limb swelling following lymphatic disruption. This results in decreased lymph flow through the collecting ducts and dermal backflow in the subdermal lymphatics. The role of dermal lymphatics in the development of lymphedema is poorly understood. The purpose of this study is to evaluate the effect of dermal lymphatic preservation in the development of lymphedema in a murine tail experimental model. METHODS: A standard murine lymphedema tail model was used as the study control. A 3 mm circumferential excision was performed 20 mm from the base of the tail. Both collecting lymphatics adjacent to the veins were transected (Full Dermal Disruption (FDD), control, n = 6). The experimental group was a modification of the standard model consisting of two hemi circumferential skin excision and collecting lymphatics transection with 3 mm interval (Partial Dermal Disruption (PDD), experimental, n = 8) maintaining continuity of capillary lymphatics. Tail volume measurements, lymphatic clearance with near Infrared Indocyanine Green (ICG) laser lymphangiography, and histology were assessed. RESULTS: The PDD group had lower tail volumes compared to FDD till day 28 (p < 0.001). ICG lymphangiography demonstrated better lymphatic clearance in the PDD when compared to FDD (p < 0.001). Reduced dermal thickness (p = 0.004) and collagen deposition (p = 0.008) were observed in PDD. Podoplanin-positive lymphatic vessel density was higher in PDD at the unadjusted level (p = 0.014) but did not meet Bonferroni-corrected significance (α = 0.010). CONCLUSION: This study demonstrates dermal lymphatics can preserve lymphatic function despite injury to transporting lymphatic channels. Dermal lymphatics may have the potential for lymphedema prevention at the lymphatic injury site.