Lymphatic Preconditioning for Preservation of Lymphatic Function

Lymphedema is chronic swelling from lymphatic dysfunction. The vascular delay phenomenon is used in flap reconstruction to increase flap viability through staged selective partial disruption of blood supply to enhance flap survival, followed by flap transfer 7–10 days later. A similar corollary for lymphatics remains unknown. The purpose of this study was to evaluate whether lymphatic preconditioning with staged disruption of lymphatics in the murine hindlimb lymphedema model can be protective against lymphedema. C57BL/6 mice underwent 20 Gy hindlimb irradiation. Group 1 (immediate lymphatic disruption) underwent a circumferential skin incision, complete lymphatic disruption, and popliteal lymph node excision in a single-stage operation. Group 2 (delayed lymphatic disruption) underwent a semi-circumferential inguinal skin incision and dominant lymphatic transection and, 7 days later, received a circumferential skin incision, complete lymphatic transection, and popliteal lymphadenectomy. Paw thickness was measured weekly. Near-infrared laser lymphangiography and immunohistochemistry were performed on D35. Group 2 had a lower average paw thickness (p = 0.0008) and greater lymphatic clearance signal intensity at 24 h (p = 0.0035). Immunohistochemistry indicated an abundance of the lymphatic endothelial-specific marker podoplanin in Group 2 compared to Group 1 (p = 0.03). This study demonstrates evidence for a novel concept of a lymphatic delay phenomenon parallel to the well-known vascular delay phenomenon.